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Background: Annually, nearly 3 million individuals in the US are hospitalized after experiencing a traumatic injury (e.g., serious automobile crash, gunshot wound, stab injury). Many traumatically injured patients experience a trajectory of resilience. However, 20-40 % develop mental health problems such as posttraumatic stress disorder and depression; population estimates exceed 600,000 patients annually. Most trauma centers do not provide direct services to address mental health recovery, but the 2022 American College of Surgeons guidelines have established this as a priority. Cost-effective interventions are needed that meet the needs of patients at each stage of the recovery process while achieving sustainability at the level of implementation. This protocol paper describes a study that rigorously tests the Trauma Resilience and Recovery Program (TRRP), a scalable, sustainable technology-enhanced intervention to support the mental health recovery of patients who have experienced a traumatic injury., Methods: We describe a randomized controlled trial with 1-year follow up of TRRP vs. enhanced usual care with 350 traumatically injured patients, including recruitment and retention procedures, assessment, implementation and fidelity monitoring, and statistical plans., Conclusion: Novel components of our design include integration of technology-based elements, use of a stepped-care model, and implementation in a trauma center that did not previously have a mental health program. Data collected address the impact of TRRP and inform improvements to the model and its implementation in preparation for large-scale testing and implementation initiatives. This body of work is critical to informing the field as it continues to move toward national standards and recommendations., Trial Registration: NCT05497115Clinicaltrials.gov., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: To evaluate the prognostic impact of substantial lymph vascular space invasion (LVSI) on the sentinel lymph node involvement and recurrence rate of patients with apparent uterine-confined endometrial cancer., Materials and Methods: We enrolled consecutive patients with apparent confined endometrial cancer who underwent surgical staging with sentinel node mapping from 14 European reference centers. LVSI was analyzed semi-quantitatively, according to a 3-tiered scoring system classified as absent, focal, and substantial., Results: Among 2352 eligible patients, 1980 were included in the analysis. Upon final pathology 226 patients (11.4 %) had SLNs involvement. LVSI was diagnosed focal in 152 patients (7.7 %), whereas 357 patients (18.0 %) showed substantial LVSI. Focal or substantial LVSI rate were significantly higher in patients with positive SLNs when compared to patients without SLNs involvement (p < 0.0001). On overall patient-based analysis, the sensitivity, specificity, positive predictive value, and negative predictive value of LVSI for sentinel lymph node metastases were 73 %, 80 %, 32 %, and 96 %, respectively. The 3-year multivariate analysis of recurrence-free survival showed that only the presence of substantial LVSI, and grade 3 disease were associated with relapse. Neither positive sentinel lymph node, deep myometrial infiltration, nor age at surgery were statistically significant., Conclusions: In patients having undergone sentinel node biopsy, positive LVSI demonstrated moderate sensitivity and reasonable specificity in detecting SLN involvement. LVSI positivity does not correlate with nodal involvement. The presence of substantial LVSI remains a strong independent risk factor for recurrence, indicating a role for potential hematogenous dissemination in patients with early-stage disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Numbers of Earth Observation (EO) satellites have increased exponentially over the past decade reaching the current population of 1193 (January 2023). Consequently, EO data volumes have mushroomed and data storage and processing have migrated to the cloud. Whilst attention has been given to the launch and in-orbit environmental impacts of satellites, EO data environmental footprints have been overlooked. These issues require urgent attention given data centre water and energy consumption, high carbon emissions for computer component manufacture, and difficulty of recycling computer components. Doing so is essential if the environmental good of EO is to withstand scrutiny. We provide the first assessment of the EO data life-cycle and estimate that the current size of the global EO data collection is ~807 PB, increasing by ~100 PB/year. Storage of this data volume generates annual CO 2 equivalent emissions of 4101 t. Major state-funded EO providers use 57 of their own data centres globally, and a further 178 private cloud services, with considerable duplication of datasets across repositories. We explore scenarios for the environmental cost of performing EO functions on the cloud compared to desktop machines. A simple band arithmetic function applied to a Landsat 9 scene using Google Earth Engine (GEE) generated CO 2 equivalent (e) emissions of 0.042-0.69 g CO 2 e (locally) and 0.13-0.45 g CO 2 e (European data centre; values multiply by nine for Australian data centre). Computation-based emissions scale rapidly for more intense processes and when testing code. When using cloud services such as GEE, users have no choice about the data centre used and we push for EO providers to be more transparent about the location-specific impacts of EO work, and to provide tools for measuring the environmental cost of cloud computation. The EO community as a whole needs to critically consider the broad suite of EO data life-cycle impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aging populations are at increased risk of sleep deficiencies (e.g., insomnia) that are associated with a variety of chronic health risks, including Alzheimer's disease and related dementias (ADRD). Insomnia medications carry additional risk, including increased drowsiness and falls, as well as polypharmacy risks. The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBTi), but access is limited. Telehealth is one way to increase access, particularly for older adults, but to date telehealth has been typically limited to simple videoconferencing portals. While these portals have been shown to be non-inferior to in-person treatment, it is plausible that telehealth could be significantly improved. This work describes a protocol designed to evaluate whether a clinician-patient dashboard inclusive of several user-friendly features (e.g., patterns of sleep data from ambulatory devices, guided relaxation resources, and reminders to complete in-home CBTi practice) could improve CBTi outcomes for middle- to older-aged adults (N = 100). Participants were randomly assigned to one of three telehealth interventions delivered through 6-weekly sessions: (1) CBTi augmented with a clinician-patient dashboard, smartphone application, and integrated smart devices; (2) standard CBTi (i.e., active comparator); or (3) sleep hygiene education (i.e., active control). All participants were assessed at screening, pre-study evaluation, baseline, throughout treatment, and at 1-week post-treatment. The primary outcome is the Insomnia Severity Index. Secondary and exploratory outcomes span sleep diary, actiwatch and Apple watch assessed sleep parameters (e.g., efficiency, duration, timing, variability), psychosocial correlates (e.g., fatigue, depression, stress), cognitive performance, treatment adherence, and neurodegenerative and systemic inflammatory biomarkers., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gartenberg: Daniel Gartenberg is the CEO of Proactive Life Inc. (DBA, SleepSpace), the software that is described in the publication. Mueller: Melissa Mueller is a current employee at SleepSpace (Proactive Life Inc.). Roberts: Daniel M. Roberts was an employee of Proactive Life, Inc. during a portion of the preparation of the manuscript and is partially funded by NIH/NIA (R44-AG056250), via subcontract to Penn State. Schade, Gamaldo, and Russell are partially funded by NIH/NIA (R44-AG056250), via subcontract to Penn State). They declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Buxton: Within the current work, Orfeu M. Buxton received subcontract grants to Penn State from Proactive Life LLC (formerly Mobile Sleep Technologies) doing business as SleepSpace (NSF/STTR#1622766, NIH/NIA SBIR R43-AG056250, R44-AG056250). Outside of the current work, received honoraria/travel support for lectures from Boston University, Boston College, Tufts School of Dental Medicine, New York University, University of Miami, University of Utah, University of Arizona, Eric H. Angle Society for Orthodontists, Allstate, consulting for Sleep Number, and receives an honorarium for his role as the Editor-in-Chief of Sleep Health. Emert, Taylor, Nagy, and Huskey are partially funded by NIH/NIA (R44-AG056250), via subcontract to University of Arizona. They declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Study Objective: To investigate the postoperative morbidity of laparoscopic hysterectomy (LH) for endometriosis/adenomyosis in terms of operative outcomes and complications., Design: Retrospective multicentric cohort study., Setting: Eight European minimally invasive referral centers., Patients: Data from 995 patients with pathologically confirmed endometriosis and/or adenomyosis who underwent LH without concomitant urological and/or gastroenterological procedures from January 2010 to December 2020., Interventions: Total LH., Measurements and Main Results: Demographic patients' characteristics, surgical outcomes, and intraoperative and postoperative complications were evaluated. We considered major postoperative surgical-related complications, any grade 2 or more events (Clavien-Dindo score) that occurred within 30 days from surgery. Univariate analysis and multivariable models fit with logistic regression were used to estimate the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for major complications. Median age at surgery was 44 years (28-54), and about half of them (505, 50.7%) were on medical treatment (estro-progestins, progestin, or Gonadotropin hormone-releasing hormone-analogues) at the time of surgery. In association with LH, posterior adhesiolysis was performed in 387 (38.9%) cases and deep nodule resection in 302 (30.0%). Intraoperative complications occurred in 3% of the patients, and major postoperative complications were registered in 93 (9.3%). The multivariable analysis showed an inverse correlation between the occurrence of Clavien-Dindo >2 complications and age (OR 0.94, 95% CI 0.90-0.99), while previous surgery for endometriosis (OR 1.62, 95% CI 1.01-2.60) and intraoperative complications (OR 6.49, 95% CI 2.65-16.87) were found as predictors of major events. Medical treatment at the time of surgery has emerged as a protective factor (OR 0.50, 95% CI 0.31-0.81)., Conclusion: LH for endometriosis/adenomyosis is associated with non-negligible morbidity. Knowing the factors associated with higher risks of complications might be used for risk stratification and could help clinicians during preoperative counseling. The administration of estro-progestin or progesterone preoperatively might reduce the risks of postoperative complications following surgery., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To examine whether there are gender differences in letters of recommendation (LORs) written for residents applying to gynecology surgical fellowships., Design: Retrospective study., Setting: Single, academic institution., Patients: LORs for applicants to gynecology oncology, urogynecology, and minimally invasive gynecology fellowships during the 2019-2020 application cycle., Interventions: Not applicable., Measurements and Main Results: We analyzed the linguistic content of the letters for the presence of 4 summary variables and 21 word categories based on previous studies using validated computerized text analysis software. We used multivariable analysis using linear mixed models to compare linguistic characteristics of letters by applicant gender. We performed qualitative content analysis on letters and compared the frequency of code themes by gender. The mixed-method design was planned to allow for analysis of domains not captured in text analysis. Among 680 letters written for 186 applicants, 124 (18.2%) were written for men, and 556 (81.8%) were written for women. There were no differences in the least square mean (standard error) word counts for LORs written for men and women applicants, 465 (20.0) vs 458(9.4) words, p = .74. In multivariable analysis, LORs written for men were found to have higher authentic tone and more risk words (p = .005 and p = .03, respectively). LORs written for women contained more communal (relationship-oriented) words (p = .006). The qualitative analysis demonstrated that ability, interpersonal traits, surgical skills, and research were the most often mentioned themes. Comments about compassion/empathy, leadership potential, teaching, interpersonal skills, and patient rapport were found more often in letters for men. More doubt raisers (words that raise doubt or concern) were present in letters for men, but letters for both genders had similar levels of negative criticism. In contrast, comments on ability, being "drama-free," and self-awareness were found more often in letters for women., Conclusion: There were gender differences in LORs written for obstetrics and gynecology surgical subspecialty fellowship applicants indicating the presence of gender bias., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear., Methods: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints., Results: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015)., Conclusions: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events., Impact and Implications: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this work we use Raman spectroscopy for protein characterization in the frozen state. We investigate the behavior of frozen therapeutic monoclonal antibody IgG1 formulation upon thawing by Raman spectroscopy. Secondary and tertiary structure of the protein in three different mab formulations in the frozen state are followed through observation of marker bands for α-helix, β-sheet and random coil. We identify the tyrosine intensity ratio I 856 /I 830 as a marker for mab aggregation. Upon fast cooling (40 °C/min) to -80 °C we observe a significant increase of random coil and α -helical structures, while this is not the case for slower cooling (20 °C/min) to -80 °C. Most changes in the protein's secondary structure are observed in the course of thawing in the range up to -20 °C, when passing through the glass transitions and cold-crystallization of the two types of freeze-concentrated solutions formed through macro- and microcryoconcentration. An increase of protein concentration and the addition of mannitol suppress secondary structural changes but do no impact on aggregation., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Factors such as regulations and health concerns shifted daily habits, including eating behaviors, during the early months of the coronavirus disease 2019 (COVID-19) pandemic. This comprehensive narrative review synthesizes research on eating behavior changes during the early months of the pandemic (February to June 2020), including changes in amount, rate, and timing of food consumption, types and healthfulness of foods consumed, the occurrence of other specified eating behaviors (eg, restrained eating or binging), and reasons for eating (eg, stress or cravings), among adults. A literature search using three EBSCOhost databases and Google Scholar was conducted to identify relevant articles made available in 2020. A total of 71 articles representing 250,715 individuals from more than 30 countries were reviewed. Findings show eating behaviors changed little during the early COVID-19 pandemic for most participants. Among those whose eating behaviors changed, increases in both intake and frequency of eating meals and snacks were more common than decreases. Findings on timing of eating and healthfulness of food consumed showed mixed results. However, when changes occurred in the type of food consumed, increases were more common for snacks, homemade pastries, white bread/pasta, legumes, and fruits/vegetables; decreases were more common for meats, seafood/fish, frozen foods, fast food, dark breads/grains, and dark leafy green vegetables. During the pandemic, binging, uncontrolled eating, and overeating increased, meal skipping decreased, and restrictive eating had mixed findings. Changes in factors such as emotions and mood (eg, depression), cravings, and environmental factors (eg, food insecurity) were related to changes in eating behaviors. Findings can inform clinical practitioners in efforts to mitigate disruptions to normal, healthy eating patterns among adults both in and outside of global health catastrophes., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Objective: Since April 2022, increasing numbers of monkeypox (MPX) cases have been reported outside endemic areas as part of an international outbreak. Our study shows aspects of clinical manifestations as well as epidemiological and virological features impacting transmission, for which only scarce data are available so far., Methods: We present a descriptive study consisting of epidemiological, clinical and virological data of four patients with confirmed MPX diagnosis. Follow-up examinations included in-depth virological investigations, including MPX virus-specific quantitative PCR and virus isolation., Results: Between 22 May 2022, and 21 June 2022, four patients with MPX were evaluated. The number of lesions ranged between one and more than 30, with asynchronous eruptions. The periorificial distribution of initial lesions together with the case histories strongly suggest human-to-human transmission during intimate contacts in sexual activities. None of the patients reported about memorable lesions on the skin of potential risk contacts. Virological sampling showed positive MPX virus-specific quantitative PCR results from swabs of the primary lesions (until day 22 after symptom onset), pharyngeal and anal mucosa, urine, seminal fluid, blood and samples of non-affected skin. Virus isolation was positive in 6/14 samples (lesional skin, anal and pharyngeal mucosa). One patient required inpatient treatment for bacterial superinfection; in another patient, three sexually transmitted co-infections were present., Conclusions: Our report demonstrates asynchronous multiple-site lesions of MPX with prolonged PCR positivity in mucosal swabs, swabs of non-affected skin, urine and seminal fluid. In addition, infectious virus was confirmed on lesional skin and mucosal swabs. The observed virological kinetics together with the suspected pre-symptomatic transmission may lead to effective and sustained human-to-human transmission, particularly in sexual networks. Preventive measures such as vaccination and post-exposure prophylaxis may become important for MPX control in vulnerable groups., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The association of pelvic organ prolapse with overactive bladder and other lower urinary tract symptoms, and the natural history of those symptoms are not well characterized. Previous cross-sectional studies demonstrated conflicting relationships between prolapse and lower urinary tract symptoms., Objective: This study primarily aimed to determine the baseline association between lower urinary tract symptoms and prolapse and to assess longitudinal differences in symptoms over 12 months in women with and without prolapse. Secondary aims were to explore associations between lower urinary tract symptoms and prolapse treatment. We hypothesized that: (1) prolapse is associated with the presence of lower urinary tract symptoms, (2) lower urinary tract symptoms are stable over time in patients with and without prolapse, and (3) prolapse treatment is associated with lower urinary tract symptom improvement., Study Design: Women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network Observational Cohort Study with adequate 12-month follow-up data were included. Prolapse and lower urinary tract symptom treatment during follow-up was guided by standard of care. Outcome measures included the Lower Urinary Tract Symptoms Tool total severity score (in addition to overactive bladder, obstructive, and stress urinary incontinence subscales) and Urogenital Distress Inventory-6 Short Form. Prolapse (yes or no) was defined primarily when Pelvic Organ Prolapse Quantification System points Ba, C or Bp were >0 (beyond the hymen). Mixed-effects models with random effects for patient slopes and intercepts were fitted for each lower urinary tract symptom outcome and prolapse predictor, adjusted for other covariates. The study had >90% power to detect differences as small as 0.4 standard deviation for less prevalent group comparisons (eg, prolapse vs not)., Results: A total of 371 women were analyzed, including 313 (84%) with no prolapse and 58 (16%) with prolapse. Women with prolapse were older (64.6±8.8 vs 55.3±14.1 years; P<.001) and more likely to have prolapse surgery (28% vs 1%; P<.001) and pessary treatment (26% vs 4%; P<.001) during the study. Average baseline Lower Urinary Tract Symptoms Tool total severity scores were lower (fewer symptoms) for participants with prolapse compared with those without (38.9±14.0 vs 43.2±14.0; P=.036), but there were no differences in average scores between prolapse groups for other scales. For all urinary outcomes, average scores were significantly lower (improved) at 3 and 12 months compared with baseline (all P<.05). In mixed-effects models, there were no statistically significant interactions between pelvic organ prolapse measurement and visit and time-dependent prolapse treatment groups (P>.05 for all regression interaction coefficients). The Lower Urinary Tract Symptoms Tool obstructive severity score had a statistically significant positive association with Pelvic Organ Prolapse Quantification System Ba, Bp, and point of maximum vaginal descent. The Lower Urinary Tract Symptoms Tool total severity scale had a statistically significant negative association with Pelvic Organ Prolapse Quantification System Ba and point of maximum vaginal descent. No other associations between prolapse and lower urinary tract symptoms were significant (P>.05 for all regression coefficients). Symptom differences between prolapse groups were small: all regression coefficients (interpretable as additive percentage change in each score) were between -5 and 5 (standard deviation of outcomes ranged from 14.0-32.4)., Conclusion: Among treatment-seeking women with urinary symptoms, obstructive symptoms were positively associated with prolapse, and overall lower urinary tract symptom severity was negatively associated with prolapse. Lower Urinary Tract Symptoms Tool scores improved over 12 months regardless of prolapse status, including in those with treated prolapse, untreated prolapse, and without prolapse., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Objective: To describe the proportion of female faculty in departmental administrative and educational leadership roles in Obstetrics and Gynecology departments., Design: Cross-sectional observational study (II-3)., Setting: Accredited Obstetrics and Gynecology residency programs., Participants: A total of 288 accredited residency programs were identified from 2019 to 2020 with 1237 individuals in leadership positions., Interventions: Similar to a 2012 to 2013 survey by Hofler et al, residency program websites and corresponding fellowships (Maternal Fetal Medicine, Female Pelvic Medicine and Reconstructive Surgery, Reproductive Endocrinology and Infertility, and Gynecologic Oncology), departmental websites, and divisional websites were queried for those in administrative and educational leadership positions. Information regarding gender (as determined by the surrogates of name and photographic gender expression), medical and academic degrees, academic rank, and subspecialty certification was abstracted., Measurements and Main Results: Within administrative leadership roles, women comprised 29% of chairs, 46% of vice chairs, and 47% of division directors, all significantly lower than men in administrative leadership (p <.001). In educational leadership, women made up 71% of medical school clerkship directors, 58% of residency directors, and 50% fellowship directors. Women were more likely to hold educational leadership positions (56% vs 40%; p <.001), although men were more likely to hold administrative leadership positions (68% vs 52%; p <.001). Among subspecialties, there was greatest gender equity within Female Pelvic Medicine and Reconstructive Surgery. Female leaders were more likely to have received additional academic degrees (e.g. MBA, MPH) than their male counterparts (19% vs 13%; p = .002)., Conclusion: Women continue to be underrepresented in administrative leadership positions. Compared with 2012 to 2013, there is only a 9% increase in proportion of women chairing and 10% vice chairing Obstetrics and Gynecology departments; however, the increase is more substantial in other positions, such as division directors (17%). Our findings demonstrate ongoing gender disparity in the highest levels of departmental leadership and the need to further improve on diversity and gender equity within leadership roles., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Objectives: This study explores the association between baseline impaired global cognitive function and changes in global cognitive function and depression among geriatric patients undergoing acute course electroconvulsive therapy (ECT)., Design: Retrospective cohort study., Setting: Single freestanding psychiatric hospital., Participants: Patients aged 50 and older receiving ECT., Interventions: 10 ECT treatments., Measurements: Cognitive assessments with the Montreal Cognitive Assessment (MoCA). Depression assessment with the Quick Inventory of Depressive Symptomatology Self Report 16 item scale (QIDS)., Results: Baseline and follow-up data were available for 684 patients. On average, patients with baseline normal cognition (MoCA ≥26; N = 371) had a decrease in MoCA of -1.44±0.26 points over the course of treatment, while those with baseline impaired global cognitive function (MoCA <26; N = 313) had an increase in MoCA of 1.72±0.25 points. Baseline cognitive status was not associated with a differential response on the QIDS., Conclusions: Patients with baseline impaired global cognitive function did not demonstrate a worsening in cognition following ECT, and baseline global cognitive function was not associated with a differential change in depression with ECT. These results suggest that impaired global cognitive function should not be viewed as a contraindication to ECT in geriatric patients., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

A short period (1-2 h) of hypothermic oxygenated machine perfusion (HOPE) after static cold storage is safe and reduces ischemia-reperfusion injury-related complications after liver transplantation. Machine perfusion time is occasionally prolonged for logistical reasons, but it is unknown if prolonged HOPE is safe and compromises outcomes. We conducted a multicenter, observational cohort study of patients transplanted with a liver preserved by prolonged (≥4 h) HOPE. Postoperative biochemistry, complications, and survival were evaluated. The cohort included 93 recipients from 12 European transplant centers between 2014-2021. The most common reason to prolong HOPE was the lack of an available operating room to start the transplant procedure. Grafts underwent HOPE for a median (range) of 4:42 h (4:00-8:35 h) with a total preservation time of 10:50 h (5:50-20:50 h). Postoperative peak ALT was 675 IU/L (interquartile range 419-1378 IU/L). The incidence of postoperative complications was low, and 1-year graft and patient survival were 94% and 88%, respectively. To conclude, good outcomes are achieved after transplantation of donor livers preserved with prolonged (median 4:42 h) HOPE, leading to a total preservation time of almost 21 h. These results suggest that simple, end-ischemic HOPE may be utilized for safe extension of the preservation time to ease transplantation logistics., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

The chemical quality of dissolved organic matter (DOM) and the speciation of nitrogen exported from urban catchments is of great importance to biogeochemical cycling in riverine and coastal receiving waters. Many urban streams in Mediterranean climates have a flashy hydrologic regime, which would suggest a rapid pulsing and shunting of solutes downstream. However, the role of these systems both as passive pipes for solute transport or as reactors for DOM and nutrient transformation is still an open question for urban, Mediterranean streams. To address this question, we evaluated changes in concentrations of inorganic and organic solutes and DOM optical properties in Alvarado Creek, a perennially-flowing, urban, first-order tributary of the San Diego River in San Diego, CA, USA, during dry weather (baseflow) conditions and during four storm events in 2016-2018. Chloride and sulfate concentrations corroborate the supposed saline groundwater supply that maintains perennial flow and brackish nature in this urban stream. During dry weather, high proportions of protein-like fluorescent component (AC4) and downstream decreases in total dissolved nitrogen (TDN) and nitrate imply in-stream processing (nitrification and denitrification). By contrast, storm hysteresis curves indicate that the supply of DOM and TDN was not exhausted over the duration of a storm event, whereas nitrate was eventually depleted, presumably because nitrification could not keep up with the export of nitrate from source areas. Rapid decreases in chloride during the storm hydrograph coincided with a shift in specific ultraviolet absorbance (SUVA) and fluorescence index (FI) to more terrestrially-derived and aromatic carbon sources, most likely from interflow of stormwater through vadose zone soils. On an annual basis, the export of microbially-derived DOM during dry weather was higher than the export of terrestrially-derived DOM during storm events; both represent important carbon inputs to coastal waters., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values., Methods: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75 th -percentile was considered., Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk., Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials., Lay Summary: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: There is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study., Method: After achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test)., Results: With the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility., Conclusion: To our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression., (Published by Elsevier Inc.)

In donation after circulatory death (DCD), cardiac grafts are subjected to warm ischemia in situ, prior to a brief period of cold, static storage (CSS) at procurement, and ex situ, normothermic, machine perfusion (NMP) for transport and graft evaluation. Cold ischemia and normothermic reoxygenation during NMP could aggravate graft injury through continued accumulation and oxidation, respectively, of mitochondrial succinate, and the resultant oxidative stress. We hypothesized that replacing CSS with hypothermic, oxygenated perfusion (HOPE) could provide cardioprotection by reducing cardiac succinate levels before NMP. DCD was simulated in male Wistar rats. Following 21 minutes in situ ischemia, explanted hearts underwent 30 minutes hypothermic storage with 1 of the following: (1) CSS, (2) HOPE, (3) hypothermic deoxygenated perfusion (HNPE), or (4) HOPE + AA5 (succinate dehydrogenase inhibitor) followed by normothermic reperfusion to measure cardiac and metabolic recovery. After hypothermic storage, tissue ATP/ADP levels were higher and succinate concentration was lower in HOPE vs CSS, HNPE, and HOPE + AA5 hearts. After 60 minutes reperfusion, cardiac function was increased and cellular injury was decreased in HOPE compared with CSS, HNPE, and HOPE + AA5 hearts. HOPE provides improved cardioprotection via succinate oxidation prior to normothermic reperfusion compared with CSS, and therefore is a promising strategy for preservation of cardiac grafts obtained with DCD., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

This study aimed to investigate the association of adenomyosis with fertility, pregnancy and neonatal outcomes. An electronic search was conducted using the MEDLINE, PubMed and Cochrane databases up to April 2020. Seventeen observational studies were included. Adenomyosis was significantly associated with a lower clinical pregnancy rate (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.51-0.94) and higher miscarriage rate (OR 2.17; 95% CI 1.25-3.79) after treatment with assisted reproductive technology (ART). The lower clinical pregnancy rate was more significant in the subgroup of patients with short down-regulation protocols. Similar associations were recorded after age adjustment. Adenomyosis was also significantly associated with an increased risk of pre-eclampsia, preterm delivery, Caesarean section, fetal malpresentation, small for gestational age infancy and post-partum haemorrhage, which was confirmed after correction for age and mode of conception. In conclusion, adenomyosis is associated with negative effects on fertility after ART. The potentially protective role of the ultra-long down-regulation protocols needs further evaluation in randomized controlled studies. Adenomyosis is also associated (independently of the mode of conception) with adverse pregnancy and neonatal outcomes. Proper counselling prior to ART and close monitoring of pregnancy in patients with adenomyosis should be recommended., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Objective: To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer., Design: Multicenter retrospective study., Setting: Three gynecologic oncology referral centers., Patients: Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018., Interventions: LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics., Measurements and Main Results: Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p <.001). The subanalysis of patients with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer showed that patients undergoing preoperative conization (vs cervical biopsy) were less likely to experience a recurrence (odds ratio 0.09; 95% confidence interval 0.01-0.55)., Conclusion: We confirmed that LRH was associated with a recurrence rate similar to that reported in the Laparoscopic Approach to Cervical Cancer trial. Tumor size ≥2 cm represents the most important risk factor influencing disease-free survival. However, we found that preoperative conization plays a potentially protective role in patients with an IB1 tumor., (Copyright © 2020. Published by Elsevier Inc.)

Study Objective: To determine if there were differences in intra-abdominal pressure (IAP) in the supine, low lithotomy, and high lithotomy positions., Design: Prospective cohort study., Setting: University medical center., Patients: Twenty-nine women undergoing surgery for prolapse or stress incontinence., Interventions: Relevant medical history, including the pelvic organ prolapse quantification stage, body mass index, and airway grade (Mallampati score), was abstracted from patients' medical charts. IAP was measured in centimeters of water (cmH 2 O) on the day of their surgery before induction of general or intravenous anesthesia using a T-doc air charged urodynamic catheter (Laborie Aquarius; Ontario, Canada) placed in a patient's vagina (for patients with incontinence) or rectum (for patients with prolapse)., Measurements and Main Results: IAP was measured in 3 positions: supine (legs at 0°), low lithotomy (legs in Yellowfin stirrups at 45°; Allen Medical, Acton, MA), and high lithotomy (legs at 90°). The means ± SDs IAP for the groups were as follows: in the supine position, 18.6 cmH 2 O ± 7.6; low lithotomy, 17.7 cmH 2 O ± 6.6; and high lithotomy, 17.1 cmH 2 O ± 6.3. In the same women, there was a significant decrease in IAP from the supine to high lithotomy positions, with a mean difference of 1.4 cmH 2 O ± 3.7, p = .05. Similarly, there was a significant, though smaller, decrease in mean IAP when moving from the supine to low lithotomy positions in these same women (mean decrease of 0.9 cmH 2 O ± 1.5, p = .004). Neither change is clinically significant based on previous research that suggests 5 cmH 2 O is a clinically significant change., Conclusion: Placing patients' legs in a low or high lithotomy position does not result in a clinically significant increase in IAP. Therefore, surgeons and anesthesiologists can consider positioning patients' lower extremities in stirrups while patients are awake to minimize discomfort and possibly reduce the risk of nerve injuries., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

The ubiquitous coronavirus 2019 (COVID-19) pandemic has required healthcare providers across all disciplines to rapidly adapt to public health guidelines to reduce risk while maintaining quality of care. Electroconvulsive therapy (ECT), which involves an aerosol-generating procedure from manual ventilation with a bag mask valve while under anesthesia, has undergone drastic practice changes in order to minimize disruption of treatment in the midst of COVID-19. In this paper, we provide a consensus statement on the clinical practice changes in ECT specific to older adults based on expert group discussions of ECT practitioners across the country and a systematic review of the literature. There is a universal consensus that ECT is an essential treatment of severe mental illness. In addition, there is a clear consensus on what modifications are imperative to ensure continued delivery of ECT in a manner that is safe for patients and staff, while maintaining the viability of ECT services. Approaches to modifications in ECT to address infection control, altered ECT procedures, and adjusting ECT operations are almost uniform across the globe. With modified ECT procedures, it is possible to continue to meet the needs of older patients while mitigating risk of transmission to this vulnerable population., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare the 30-day incidence of deep or organ-space and/or superficial incisional surgical site infections (SSIs) by the subtype of laparoscopic hysterectomy and to report on additional risk factors for SSIs following laparoscopic hysterectomy., Design: Retrospective cohort study., Setting: American College of Surgeons National Surgical Quality Improvement Program Database., Patients: Women undergoing laparoscopic hysterectomy from 2012 to 2014., Interventions: Women were stratified into 3 groups by the type of hysterectomy: total laparoscopic hysterectomy (TLH), laparoscopic-assisted vaginal hysterectomy (LAVH), and laparoscopic supracervical hysterectomy (LSCH). Demographic and clinical characteristics were compared for the 3 groups using the Kruskal-Wallis test or 1-way analysis of variance, where appropriate, for continuous variables and the chi-square or Fisher's exact test for categoric variables. Post hoc analyses were performed for multiple comparisons. Univariate analyses to examine the association with SSI were performed using the t test or Wilcoxon rank sum test as appropriate for continuous variables and the chi-square test or Fisher's exact test as appropriate for categoric variables. Significant variables on univariate analysis were included in a stepwise, backward multivariable logistic regression to identify the independent risk factors of SSI., Measurements and Main Results: In total, 46 755 women underwent laparoscopic hysterectomy. Most were classified as TLH (26 009, 56%), followed by LAVH (13 884, 30%), and LSCH (6862, 14%). The overall rate of 30-day deep or organ-space SSI was 1.8% (n = 445). Thirty-day deep or organ-space SSI was lower in women who underwent LSCH (0.6%) than in women who underwent TLH (1.0%) or LAVH (1.1%; p = .001), but there was no difference in the incidence of superficial incisional SSI (0.8%, 0.8%, and 0.8% for TLH, LAVH, and LSCH, respectively; p = .75). On multivariate regression analysis, LSCH remained independently associated with a decreased risk of deep or organ-space SSI (adjusted odds ratio, 0.60; 95% confidence interval, 0.43-0.84; p = .003). In addition, relative to the women who were discharged on the same day, women admitted for >24 hours had 2-fold increased odds of deep or organ-space SSI. Asian race, smoking, perioperative transfusion, dirty or infected cases, and American Society of Anesthesiologist class 3 were associated with increased odds for deep or organ-space SSI. Length of stay >24 hours and Native Hawaiian/Pacific Islander race were associated with increased odds of superficial incisional SSI., Conclusion: LSCH is associated with a decreased risk of deep or organ-space SSI compared with other subtypes of laparoscopic hysterectomy. Same-day discharge after laparoscopic hysterectomy is associated with decreased odds of SSI., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Mindset and communication barriers may hinder the acceptance of bariatric surgery (BS) by the eligible patient population., Objectives: To improve the understanding of expectations, opinions, emotions, and attitudes toward weight loss among patients with obesity., Setting: Switzerland, Germany, Austria., Methods: Survey data collected from BS-related social media communities (n = 1482). Participants were asked to write 5 words that first came to their mind about "weight loss," and to select 2 emotions, which best described their corresponding feelings. Demographic and obesity-related data were collected. Cognitive representations were constructed based on the co-occurrence network of associations, using validated data-driven methodology., Results: Respondents were Caucasian (98%), female (94%), aged 42.5 ± 10.1 years, current/highest lifetime body mass index = 36.9 ± 9/50.7 ± 8.7 kg/m 2 . The association network analysis revealed the following 2 cognitive modules: benefit-focused (health, attractiveness, happiness, agility) and procedure-focused (effort, diet, sport, surgery). Patients willing to undergo BS were more benefit-focused (odds ratio [OR] = 2.4, P = .02) and expressed more "hope" (OR = 142, P < .001). History of BS was associated with higher adherence to the procedure-focused module (OR = 2.3, P < .001), and with increased use of the emotions "gratitude" (OR = 107, P < .001), "pride" (OR = 15, P < .001), and decreased mention of "hope" (OR = .03, P < .001)., Conclusion: Patients with obesity in our study tend to think about weight loss along 2 cognitive schemes, either emphasizing its expected benefits or focusing on the process of achieving it. Benefit-focused respondents were more likely to consider BS, and to express hope rather than gratitude or pride. Novel communication strategies may increase the acceptance of BS by incorporating weight loss-related cognitive and emotional content stemming from patients' free associations., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia-inducible factor-1α, nuclear factor erythroid 2-related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O 2 uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In multiple sclerosis (MS) exercise improves upper limb functions, but it is unclear what training types are more effective., Objective: This study compares robot-assisted training based on haptic or sensorimotor exercise., Methods: 41clinically definite MS subjects with upper limb impairment were randomised into two groups: (i) Haptic and (ii) Sensorimotor. Subjects in the Haptic performed a robot-assisted training protocol designed to counteract incoordination and weakness. The task -interaction with a virtual mass-spring system against a resistive load- requires coordination skills. Task difficulty and magnitude of resistive load were automatically adjusted to the individual impairment. Subjects in the Sensorimotor performed reaching movements under visual control; the robot generated no forces. Both groups underwent eight training sessions (40 min/session, 2 sessions/week). Treatment outcome were 9HPT and ARAT scores., Results: The average 9HPT score decreased from 74±9 s to 61±8 s for the Haptic and from 49±6 s to 44±6 s. We found a significant Treatment (p=.0453) and Time differences (p=.005), but no significant Treatment×Time interactions although we found that the absolute change was only significant in the Haptic group (p=.011). We observed no significant changes in the ARAT score. Participants tolerated treatments well with a low drop-out rate. In the subjects evaluated at after 12 week (11 subject in sensory-motor and 17 in haptic group) no retention of the effect was found., Conclusions: Task oriented training may improve upper limb function in persons with MS especially in prevalent pyramidal impaired subjects without maintain the effects after three months., Clinical Trial Registration Number: NCT02711566 (clinicaltrial.gov)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: There is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study., Methods: Elderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05., Results: A total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest., Conclusion: This is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable., (Copyright © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Fishes in European rivers are threatened by manifold stressors such as structural degradation, water pollution, overexploitation, land-use changes in the catchment, invasive species and global processes including climate change. Identifying main stressors in a stream/river system is of utterly importance for efficiently utilizing the scarce funds for conservation measures in order to achieve the best possible outcome. Within 203 headwater streams of Rhine, Elbe and Danube, we quantified the relative influence of different environmental stressors (water chemistry, food availability (macroinvertebrates), terrestrial predators) and anthropogenic stressors (land use, structural modification of streams) on fish assemblages at different spatial scales based on multivariate biota-environment models. In our analyses, the predictor variables percentage of impoundments, crop farming (especially erosion-prone crops such as maize) and ground sealing in the catchments, the number of wastewater treatment plants and biogas plants in the catchments as well as structural modifications of river banks were most often identified as stressors influencing fish community composition. However, the effects of the stressors varied between the investigated survey-area scales (two different catchments sizes and riparian strips) and regionally (entire study area, major drainage systems, river catchments, stream sizes, geographical subregions). In most cases, fish community composition was simultaneously affected by multiple stressors, underpinning the need for a more holistic and ecosystem-based approach in freshwater conservation and restoration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Context: Exacerbated by life stressors, fatigue is the most common symptom for people living with HIV., Objective: To adapt, develop, and assess the feasibility of a Cognitive Behavioral Stress Management Mobile Health (CBSM mHealth) application (app) for HIV-related fatigue., Methods: This study had two phases: app development with key informants (N = 5) and a randomized controlled trial (N = 30). Patients randomized to the intervention group completed 10 weekly CBSM modules; those in the control group received a generic healthy lifestyle app. Measures included HIV-related fatigue, depression, anxiety, stressful life events, CD4 count, HIV viral load, credibility and acceptability of the intervention, and barriers to treatment participation., Results: We were able to recruit participants for this study, and they were able to complete the required measures. They found the intervention to be credible and acceptable and reported few barriers to treatment participation. The direction of change in the primary outcome, a decrease in fatigue, is in the expected direction and provides evidence of the promise of the intervention, which still needs to be tested in an adequately powered trial. For completers (randomized to the intervention group and completed at least 80% of the modules), there were significant changes (95% CI; lower scores indicate improvement) in fatigue intensity (from 64.2 to 59.7) and overall fatigue-related functioning (from 6.6 to 4.2)., Conclusion: We have proof of concept as to the feasibility, acceptability, and initial signals of efficacy for an mHealth intervention to help people with HIV-related fatigue better cope with stress and reduce their fatigue., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications., Methods: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed., Findings: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab., Interpretation: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications., Funding: Teva Pharmaceuticals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

It is often difficult to accurately localize small arteries in images of peripheral organs, and even more so with vascular abnormality vasculatures, including collateral arteries, in peripheral artery disease (PAD). This poses a challenge for manually sampling arterial input function (AIF) in quantifying dynamic contrast-enhanced (DCE) MRI data of peripheral organs. In this study, we designed a multi-step screening approach that utilizes both the temporal and spatial information of the dynamic images, and is presumably suitable for localizing small and unpredictable peripheral arteries. In 41 DCE MRI datasets acquired from human calf muscles, the proposed method took <5 s on average for sampling AIF for each case, much more efficient than the manual sampling method; AIFs by the two methods were comparable, with Pearson's correlation coefficient of 0.983 ± 0.004 (p-value < 0.01) and relative difference of 2.4% ± 2.6%. In conclusion, the proposed temporospatial-feature based method enables efficient and accurate sampling of AIF from peripheral arteries, and would improve measurement precision and inter-observer consistency for quantitative DCE MRI of peripheral tissues., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Intensification of catchment land-use and the corresponding habitat degradation pose a threat to freshwater biodiversity and ecosystem health, yet few studies comprehensively quantified the effects of specific land-use variables on fish communities for different catchments within the same climatic region. Herein, we investigated the influence of catchment land use on fish community composition in the headwater areas of the European main river systems Elbe, Danube and Main/Rhine. The analyses comprising 289 streams and rivers in Bavaria, southern Germany, revealed that the influence of urbanization (e.g. ground sealing), potamalisation (impoundment of water courses), and erosion-prone, agricultural land-use types (e.g. root crop, maize) were significantly related to the fish community composition. In addition, multiple stressors were effective indicators and their importance differed between survey-area scales, geographical regions, and stream sizes. The findings suggest that terrestrial effects of land-use and urbanization need to be more strongly considered in the conservation of endangered stream fishes, ideally including combined measures of erosion control, restoration of environmental flows and mitigation of structural degradation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes., Methods: In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks' gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-to-treat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600., Findings: Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41-70). The mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23 (95% CI -2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis., Interpretation: Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population., Funding: US National Institutes of Health, US Food and Drug Administration, Thrasher Research Fund, Australian National Health and Medical Research Council, Health Technologies Assessment-National Institute for Health Research (UK), Australian and New Zealand College of Anaesthetists, Murdoch Children's Research Institute, Canadian Institutes of Health Research, Canadian Anesthesiologists Society, Pfizer Canada, Italian Ministry of Health, Fonds NutsOhra, UK Clinical Research Network, Perth Children's Hospital Foundation, the Stan Perron Charitable Trust, and the Callahan Estate., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Analysis of long-term speech and swallowing function and subjective quality of life (QOL) after primary resection and sentinel node biopsy (SNB) in patients with early stage (cT1/T2) oral squamous cell carcinomas (OSCC)., Material and Methods: Eighty-one consecutive patients treated primarily by transoral resection without flap reconstruction and SNB for a cT1/T2 OSCC were included. Completion neck dissection (CND) was indicated in case of occult disease in the sentinel nodes. Adjuvant radiation (aRT) was administered according to the ultimate lymph node status. All patients showed no evidence of disease at time of analysis. Speech and swallowing function were assessed using standardized clinical examinations (11-item, articulation test) and validated questionnaires on subjective QOL (MDADI, FIGS). Median follow-up was 60 months (range 13-159 months) after initial treatment., Results: In all assessments for speech and swallowing, the entire study cohort achieved very high scores, with mean values located in the highest 10% of the scales. Neither tumor size nor site, age, pN-category, CND, and aRT had significant impact on functional outcomes and subjective QOL with the exception of lower scores in the global and physical scores of MDADI after CND or aRT, and articulation in the population over 60 years of age., Conclusion: Transoral resection without reconstruction and SNB for early OSCC achieves excellent outcome with regard to speech, swallowing and subjective QOL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Racial and ethnic minorities consistently demonstrate disparate post-stroke outcomes. However, there is a paucity of literature related to whether this disparity exists specifically in post-stroke cognitive decline., Objective: To determine if racial and ethnic disparities exist in post-stroke subjective cognitive decline (SCD) among non-Hispanic Blacks (Blacks), American Indians or Alaska Natives (AI/ANs), Hispanics, and non-Hispanic Whites (Whites) in the United States using data from the Behavioral Risk Factor Surveillance System (BRFSS)., Methods: A retrospective analysis was completed using the 2016 BRFSS data in adults who self-reported stroke and SCD. Descriptive statistics were completed for baseline comparisons using chi squared tests for categorical variables. A binary logistic regression controlling for baseline differences was completed to examine racial and ethnic differences in SCD., Results: Significant differences in SCD were identified across all racial and ethnic groups. When compared to Whites, Blacks, AI/ANs, and Hispanics more frequently reported worsening confusion or memory loss that interfered with day-to-day activities and the ability to work, volunteer, and engage in social activities outside of the home. AI/ANs who reported SCD were more likely than Whites to have help available. Hispanic persons with SCD or their family members were most likely to discuss SCD with a healthcare provider., Conclusion: Although persons from all racial and ethnic groups in this study experienced some degree of SCD, Blacks, AI/ANs, and Hispanics most frequently reported worsening confusion or memory loss impacting engagement in day-to-day activities and the ability to work, volunteer, and engage in social activities outside of the home., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 patients with MPN, including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4 (5.8%) of 69 patients receiving JAK1/2 inhibition compared with 2 (0.36%) of 557 with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 patients with MPN. Considering primary myelofibrosis only (N = 216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) vs 1 (0.54%) of 185 control patients. Lymphomas were of aggressive B-cell type, extranodal, or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a preexisting B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1 -/- mice: 16 of 24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a preexisting B-cell clone may identify individuals at risk., (© 2018 by The American Society of Hematology.)

Study Objective: To evaluate the added value of the fluorescence dye indocyanine green (ICG) for sentinel lymph node (SLN) mapping in women with cervical cancer who had undergone previous conization (stage 1A-1B1) by comparing ICG versus Tc99 m radiotracer + blue dye (BD)., Design: Retrospective study (Canadian Task Force classification II-2)., Setting: Two European academic medical centers, San Gerardo Hospital, Italy and University of Berne, Switzerland., Patients: Sixty-five women with early stage (IA-IB1) cervical cancer who had undergone previous conization and who underwent SLN mapping with Tc99 m  ± BD (n = 23) or ICG (n = 42) followed by pelvic lymphadenectomy and fertility-sparing surgery or hysterectomy were included in this analysis., Intervention: Overall detection rate and bilateral SLN mapping rates of ICG were compared with those obtained using the standard Tc99 m radiocolloid and BD., Measurement and Main Results: Overall, 220 SLNs were detected. The median number of SLNs per patient in the Tc99 m  ± BD group was 2 (range, 1-5) and in the ICG group, 3 (range, 2-15). The detection rate of SLNs was 95.7% in Tc99 m  ± BD group and 100% in the ICG group (p = .354). The women injected with ICG had a higher rate of bilateral mapping of the SLNs as compared with the Tc99 m  ± BD group (95.2% vs 69.6%, p = .016%). Only 12% of the patients (8/65) presented metastatic nodes, 2 in the Tc99 m  ± BD group and 6 in the ICG group., Conclusion: In early-stage cervical cancer patients conization had no significant impact on the SLN detection rate using both techniques (ICG and radiotracer ± BD). In this scenario a higher bilateral mapping rate was confirmed using the fluorescent dye ICG rather than the standard techniques., (Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare sentinel lymph node (SLN) mapping in women with cervical cancer stage >IB1 (tumor size >2 cm) using indocyanine green (ICG) versus the standard technique using radioisotope technetium 99m radiocolloid (Tc99 m ) radiotracer with or without blue dye., Design: European multicenter, retrospective observational study (Canadian Task Force classification II-2)., Setting: Four academic medical centers., Patients: Ninety-five women with stage IB1 cervical cancer (>2 cm) who underwent SLN mapping with Tc99 m with or without blue dye or ICG and radical hysterectomy., Intervention: The detection rate and bilateral mapping rate were compared between ICG and standard Tc99 m radiotracer with or without blue dye. Lymphadenectomy was performed, and the false-negative rate was assessed., Measurements and Main Results: Forty-seven patients underwent SLN mapping with Tc99 m with or without blue dye, and 48 did so with ICG. All patients underwent radical hysterectomy with or without bilateral salpingo-oophorectomy between 2008 and 2016. The overall detection rate of SLN mapping was 91.5% for Tc99 m with or without blue dye and 100% for ICG. A 91.7% rate of bilateral migration was achieved for ICG, significantly higher than the 66% obtained with Tc99 m with or without blue dye (p = .025). Nine of the 23 SLN-positive patients (39.1%) were diagnosed exclusively as a result of the ultrastaging used to identify micrometastases or isolated tumor cells only., Conclusions: In advanced cervical cancer (stage IB1 >2 cm), the detection rate and bilateral migration rate on real-time fluorescent SLN mapping were higher with ICG than with Tc99 m radiotracer with or without blue dye. SLN mapping and ultrastaging can provide additional information for nodal staging in advanced cervical cancer. In this setting, ICG is a promising tool for mapping, appearing less affected by higher disease stage compared with traditional methods., (Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.)