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The purpose of this study was to examine the relationships between athletic motor skill competencies (AMSC), maturation, sex, body mass index, physical performance, and psychological constructs (motivation to exercise, physical self-efficacy, and global self-esteem). Two-hundred and twenty-four children aged 11–13 years old were included in the study and sub-divided by sex. The athlete introductory movement screen (AIMS) and tuck jump assessment (TJA) were used to assess AMSC, while standing long jump distance assessed physical performance. Online surveys examined participants’ motivation to exercise, physical self-efficacy, and self-esteem. Trivial to moderate strength relationships were evident between AMSC and BMI (boys: rs = −0.183; girls: rs = −0.176), physical performance (boys: rs = 0.425; girls: rs = 0.397), and psychological constructs (boys: rs = 0.130–0.336; girls rs = 0.030–0.260), with the strength of relationships different between the sexes. Higher levels of AMSC were related to significantly higher levels of physical performance (d = 0.25), motivation to exercise (d = 0.17), and physical self-efficacy (d = 0.15–0.19) in both boys and girls. Enhancing AMSC may have mediating effects on levels of physical performance and psychological constructs in school-aged children, which may hold important implications for physical activity levels and the development of physical literacy.

Background. Orthostatic hypotension (OH) is a poorly understood complication of simultaneous pancreas–kidney (SPK) transplantation. We sought to determine the incidence, timing, and relationship of OH to rapid glycemic control in the early posttransplant period. Methods. This was a nonrandomized retrospective single-center review of 75 SPK and 19 kidney-alone (KA) recipients with type 1 diabetes (DM). Results. OH occurred in 57 (76%) SPK versus 2 (10%) KA recipients (odds ratio [OR] 61.72, 95% confidence interval [CI], 9.69-393.01; P < 0.001). The median onset of OH was 12 (interquartile range [IQR] 9–18) days posttransplant and resolved in 85% of SPK recipients after a median of 2.5 (IQR 1.2–6.3) months. Among SPK recipients, independent risk factors for OH were a shorter duration of DM (OR 0.85, 95% CI, 0.73-0.98; P = 0.03) and rapid glycemic control in the early posttransplant period (OR 1.13, 95% CI, 1.01-1.27; P = 0.04), as evidenced by a larger percent change in hemoglobin A1c (HbA1c) from transplant to month 3. OH patients had a higher median baseline HbA1c [8.3% (IQR 7.2–10.0) versus 7.1% (IQR 6.8–8.3); P = 0.07], lower median 3-month HbA1c [4.8% (IQR 4.6–5.2) versus 5.2% (IQR 5.0–5.4); P = 0.02], and a larger reduction in HbA1c over time as compared to recipients without OH (P < 0.01). Conclusions. Our results show that OH is more likely to occur following SPK versus KA transplantation and is strongly associated with rapid glucose normalization within the early posttransplant period.

Gaucher disease is renowned for extreme phenotypic diversity that does not show consistent genotype/phenotype correlations. In Argentina, a national collaborative group, Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher, GADTEG, delineated uniformly severe type 1 Gaucher disease manifestations presenting in childhood with large burden of irreversible skeletal disease. Here using Long-Read Single Molecule Real-Time (SMRT) Sequencing of GBA1 locus, we show that the RecNciI allele is highly prevalent and it is associated with severe skeletal manifestations with onset in childhood or in young adults. Additionally, we described novel GBA1 variants not previously described.

Summary Prior to integration into clinical care, a novel medical innovation is typically assessed in terms of its balance of benefits and risks, often referred to as utility. Members of multidisciplinary research teams may conceptualize and assess utility in different ways, which has implications within the translational genomics community and for the evidence base upon which clinical guidelines groups and healthcare payers make decisions. Ambiguity in the conceptualization of utility in translational genomics research can lead to communication challenges within research teams and to study designs that do not meet stakeholder needs. We seek to address the ambiguity challenge by describing the conceptual understanding of utility and use of the term by scholars in the fields of philosophy, medicine, and the social sciences of decision psychology and health economics. We illustrate applications of each field's orientation to translational genomics research by using examples from the Clinical Sequencing Evidence-Generating Research (CSER) consortium, and we provide recommendations for increasing clarity and cohesion in future research. Given that different understandings of utility will align to a greater or lesser degree with important stakeholders' views, more precise use of the term can help researchers to better integrate multidisciplinary investigations and communicate with stakeholders.

Background Biological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD. Methods We employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n = 27), comparing them to a control cohort of neurotypical (NT) participants (n = 35). Results Behaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group. Limitations The cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability. Conclusions Together, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition.

The proportions of individuals who are underrepresented in medicine (URiM) in ophthalmology lag behind their proportions within the US population. Diversity trends have been studied in other specialties, but literature examining trends in ophthalmology is lacking. In this study, we investigate trends in the racial and ethnic demographics of ophthalmology residents and residency applicants.Trend study.Demographic data of all residency programs across all specialties were extracted from Accreditation Council for Graduate Medical Education yearly reports from 2011 to 2019. Data from 2016 to 2019 on ophthalmology match applicants were analyzed using the 2020 Ophthalmology Residency Match Summary Report and the 2020 Association of University Professors of Ophthalmology Residency GenderEthnicity Summary. Linear trends were examined by the Cochran-Armitage test.From 2011 to 2019, the raw percentage of URiM ophthalmology residents increased from 4.7% (66/1419) to 5.8% (85/1473) (P.001) whereas that of surgical specialties decreased from 9.9% (2164/21,967) to 9.1% (2370/26,082) (P.001). The percentage of URiM ophthalmology match applicants increased from 5.9% (43/726) of all applicants to 11.8% (87/741) from 2016 to 2019 (P.001), and the percentage of URiMs matching into ophthalmology increased from 4.9% (23/467) of all participants to 10.8% (52/484) from 2016 to 2019 (P.001).Although there has been a positive trend in the percentage of URiMs applying and matching into ophthalmology, a lack of racial and ethnic diversity relative to other specialties persists. Strategies are needed to increase diversity in the field.

Importance Head and neck cancer (HNC) survivors are about twice as likely to die by suicide compared with other cancer survivors. Objective To examine the associations between precancer mental health and pain and postcancer receipt of mental health, substance use disorder (SUD), or palliative care services with risk of suicidal self-directed violence (SSDV). Design, setting, and participants This retrospective cohort study used the Veterans Health Administration data of 7803 veterans with a diagnosis of HNC (stage I-IVB) who received cancer treatment between January 1, 2012, and January 1, 2018. Data were analyzed between May 2020 and July 2021. Exposures Presence of precancer chronic pain and SUD diagnoses, and postcancer SUD, mental health, or palliative care treatment. Exposures were defined using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes in Veterans Health Administration administrative data. Main outcomes and measures Documented SSDV event, including suicide attempt or death by suicide, after HNC diagnosis. Results Among the cohort of 7803 veterans (7685 [98.4%] male; mean [SD] age, 65 [10.7] years), 72 (0.9%) had at least 1 documented SSDV event following their cancer diagnosis, and 51 (0.7%) died by suicide. Four adjusted modified Poisson regression analyses identified that precancer chronic pain (incidence rate ratio [IRR], 2.58; 95% CI 1.54-4.32) or mood disorder diagnoses (IRR, 1.95; 95% CI, 1.17-3.24) were associated with higher risk of postcancer SSDV. Those who had at least 1 documented mental health (IRR, 2.73; 95% CI, 1.24-6.03) or SUD (IRR, 3.92; 95% CI, 2.46-6.24) treatment encounter in the 90 days following HNC diagnosis were at higher risk for SSDV. A palliative care encounter within 90 days of postcancer diagnosis was associated with decreased risk of SSVD (IRR, 0.49; 95% CI, 0.31-0.78). Conclusions and relevance In this cohort study, a high proportion of HNC survivors with an SSVD event died from their injuries. Identification of risk factors for SSDV among HNC survivors may help direct additional resources to those who are at high risk. Referral to palliative care appears to be an important component of supportive oncologic care to reduce the risk of SSDV.

Introduction/Background* Our ever-growing population is putting greater strain upon the NHS with more complex medical problems, and strained resources. Comorbidities predispose patients to postoperative complications, impacting recovery and survival, length of stay, and mortality rates. The one size fits all attitude to treatment is no longer the best approach to tackle illness, as technology develops patient care will transform. CPET assesses the bodies neurohumoral stress response to surgery, however not all patients complete CPET, with mobility and contraindications an issue. The ability to quantify morbidity and mortality risks enables discussions regarding appropriateness of surgical interventions, discuss likely scenarios and quality of life (QOL). Methodology The aim is to create a pre-operative prediction model using cardiopulmonary exercise testing (CPET) and routine health data (RHD). The model can be utilised in conjunction with CPET, identifying patients in greater need of high dependency care (HDU), and at greater risk of complications. All gynaecological oncology patients undergoing CPET from 2011 onwards are included in the retrospective analysis in one centre, which includes those over 65 years and those with multiple comorbidities. RHD, and CPET data will be collated, assessing links between the data with known clinical outcomes, producing a risk prediction tool that will then be used on a prospective cohort of patients. Result(s)* Risk stratification tools allow shared decision making with personalised perioperative risks giving better patient experience and post-operative QOL. RHD and CPET is currently being collated and analysed using R Studio. Conclusion* The hope is to create a prediction model to use in conjunction with CPET to better guide care and improve patient outcome. If shown to better predict high risk patients it may be possible to improve care by prediction model alone, meaning all patients can be assessed, be cost effective, and be a more personalised approach to patient care.

We hope that at the point that readers see this CJASN article, they will have already read the three accompanying CJASN articles on patient preference information and patient-centered innovation in KRT ([1][1][⇓][2]–[3][3]). These four articles represent a combined effort to chronicle the

Background Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment. Methods In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients. Results The study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04–2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46–0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72–2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53–1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36–1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64–2.08, P = 0.64). Conclusions Hospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study.

Micropatterned suspension culture creates consistently sized and shaped cell aggregates but has not produced organotypic structures from stable cells, thus restricting its use in accurate disease modeling. Here, we show that organotypic structure is achieved in hybrid suspension culture via supplementation of soluble extracellular matrix (ECM). We created a viable lung organoid from epithelial, endothelial, and fibroblast human stable cell lines in suspension culture. We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of lumen-like structures with airspace showing feasible gas exchange units, formation of branching, perfusable vasculature, and long-term 70-day maintenance of lumen structure. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We also demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.

PurposeSouthSeq, a translational research study to perform genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder, was conducted in NICUs in the Southeastern US. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas that are historically under-represented in genomic medicine research.MethodsGS and analysis were performed for 367 newborns to detect disease-causal genetic variation concurrent with standard of care evaluation and testing.ResultsDefinitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of newborns and 14% harbored an uncertain result. Only 39% of DD/LD findings were identified via concurrent standard of care suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups.ConclusionWe describe one of the largest to-date GS cohorts of ill newborns, enriched for African American and rural patients. Our results demonstrate the utility of GS as it provides early in life detection of clinically relevant genetic variation not identified via current standard clinical testing, particularly for newborns exhibiting certain phenotypic features.

Examine trends in the proportion of underrepresented minority (URM) residents from 2011 to 2019 across all specialties and investigate differences between surgical and non-surgical specialties.Cross-sectional study.N/A.The authors extracted data on the proportion of URM residents in all specialties from the Accreditation Council for Graduate Medical Education yearly reports.There was a statistically significant decline in the proportion of URM residents in surgical specialties (p0.01) from 2011 (9.9%) to 2019 (9.1%) and a significant increase in the proportion of URM residents in non-surgical specialties (p0.01) from 2011 (9.6%) to 2019 (10.2%).This study emphasizes the need to increase recruitment of URMs in medicine, especially in surgical specialties. Findings from this study can inform much-needed initiatives to address barriers to entry for diverse applicants within specialties that lack diversity and have shown minimal improvement over time.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.

Purpose The cancer survivor population is projected to increase to 22.2 million by 2030, requiring improved collaboration between oncology and primary care practices (PCP). PCPs may feel ill-equipped to provide cancer survivorship care to patients without input from cancer specialists. Compared with nonrural cancer survivors, rural cancer survivors report experiencing worse treatment-related symptoms. The goal of this study was to gain a better understanding of the perspectives of PCP teams towards survivorship care and to develop and test an interdisciplinary training program to improve cancer survivorship care in rural practice. Methods This study was conducted in two phases. First, focus groups were conducted with rural PCP teams to gather information regarding beliefs, practices, and barriers related to cancer survivorship care delivery. A thematic analysis was completed using an iterative process of reviewing transcripts. Results from phase 1 were used to inform the development of a pilot intervention tested within seven rural PCPs (phase 2). Pre- and post-intervention knowledge changes were compared, and post-session interviews assessed planned or sustained practice changes. Results Seven PCPs participated in focus groups (phase 1). Cross-cutting themes identified included (1) organizational barriers affecting the delivery of cancer survivorship care, (2) challenges of role delineation with specialists and patients, (3) difficulty accessing survivorship care and resources, and (4) providers’ lack of knowledge of cancer survivorship care. For phase 2, seven practices participated in four case-based educational sessions. Within and between practice changes were identified. Conclusion This project explored cancer survivorship perspectives among PCP teams. Lack of familiarity with evidence-based guidelines and the inability to identify cancer survivors was apparent during discussions and led to the implementation of the phase 2 intervention, iSurvive. As a result, PCPs either changed or planned changes to improve the identification and evidence-based care of cancer survivors. Implications for Cancer Survivors Address barriers to access cancer survivorship care in rural primary care practices.

Skilful hydrological forecasts can benefit decision-making in water resources management and other water-related sectors that require long-term planning. In Ireland, no such service exists to deliver forecasts at the catchment scale. In order to understand the potential for hydrological forecasting in Ireland, we benchmark the skill of ensemble streamflow prediction (ESP) for a diverse sample of 46 catchments using the GR4J (Génie Rural à 4 paramètres Journalier) hydrological model. Skill is evaluated within a 52-year hindcast study design over lead times of 1 d to 12 months for each of the 12 initialisation months, January to December. Our results show that ESP is skilful against a probabilistic climatology benchmark in the majority of catchments up to several months ahead. However, the level of skill was strongly dependent on lead time, initialisation month, and individual catchment location and storage properties. Mean ESP skill was found to decay rapidly as a function of lead time, with a continuous ranked probability skill score (CRPSS) of 0.8 (1 d), 0.32 (2-week), 0.18 (1-month), 0.05 (3-month), and 0.01 (12-month). Forecasts were generally more skilful when initialised in summer than other seasons. A strong correlation (ρ=0.94) was observed between forecast skill and catchment storage capacity (baseflow index), with the most skilful regions, the Midlands and the East, being those where slowly responding, high-storage catchments are located. Forecast reliability and discrimination were also assessed with respect to low- and high-flow events. In addition to our benchmarking experiment, we conditioned ESP with the winter North Atlantic Oscillation (NAO) using adjusted hindcasts from the Met Office's Global Seasonal Forecasting System version 5. We found gains in winter forecast skill (CRPSS) of 7 %–18 % were possible over lead times of 1 to 3 months and that improved reliability and discrimination make NAO-conditioned ESP particularly effective at forecasting dry winters, a critical season for water resources management. We conclude that ESP is skilful in a number of different contexts and thus should be operationalised in Ireland given its potential benefits for water managers and other stakeholders.

Background Discharge to Assess as outlined by the Department of Health was adopted in Derby in 2016. Previously the discharge pathways to community settings from the acute trust were complex. Challenges included: Operating from a traditional residential care home.No integration of community health staff and social care teams leading to delays in treatment and decision making as well as multiple referrals and hand-overs and no joint communication which was confusing for patients.Stakeholder anticipation of 6 weeks length of stay.Limited responsiveness to capacity demand within planned and unplanned community physiotherapy.Changing the culture and mind-set of staff.Different health and social care processes and procedures, IT systems, working patterns, contracts and pay scales. Methods A new service model, joint processes and standard operating procedures was developed with the patient at the centre of the design. Trusted assessment and information sharing reduce multiple assessments and hand overs, ensuring a smoother and improved patient experience. Outcomes Triage of patients from the Integrated Discharge Hub to the appropriate pathway, early discharge planning, board rounds and MDT's and timely assessments combined with an enablement ethos have increased the flow of patients through the service, decreased care package hours and increased capacity through reducing both length of stay and delayed transfers of care. The health and social care teams are now delivering fully integrated care and undertaking joint training. This has led to a reduction in treatment times from 20 days to 12 days, reductions in DTOC to average of 8 days per month and improved access to community based routine therapy from 85% of referrals being seen by 6 weeks 2017-18 to 99% in 2018-19. Conclusions The integrated service delivers more for less resulting in significant savings in the healthcare and social care system while maintaining quality standards and outcomes.

The umbilical cord (UC) connects the fetal blood supply to the placenta, so is exposed to all systemic endo- and xenobiotics. We have extensive experience using UC as an analytical matrix for detecting and/or quantitating drugs, chemicals and endogenous compounds. This technical note describes advantages (large amount available, ease of collection, small sample needed for use, rapid availability) and challenges (clinical relationships, processing difficulties, matrix effects on analytes and detection technologies) of UC as an analytical matrix in ELISA and LC/MS platforms, and provides guidance for successfully working with this tissue.

It is widely accepted that parents are a pivotal part of young people’s sporting journey, and over the last 4 decades there has been a substantial growth in research pertaining to youth sport parenting. The aim of this paper is to review the status of the literature pertaining to parenting in youth sport and suggest areas for future work. Specifically, the author provides a very brief history of sport parenting research before turning attention to the 3 areas of study that are currently attracting the majority of researchers’ attention: the influence of parental involvement in youth sport, factors affecting parental involvement in youth sport, and strategies to promote high-quality parental involvement. Future research directions pertaining to the sport parenting questions that are asked, the populations that are sampled, and the interventions that are developed and evaluated are subsequently provided. Finally, the paper concludes with some considerations for best practice in sport clubs and organizations that seek to foster more adaptive youth sport parenting.

Background and objective:In hyperacute ischaemic stroke, T2 of cerebral water increases with time. Quantifying this change may be informative of the extent of tissue damage and onset time. Our objective was to develop a user-unbiased method to measure the effect of cerebral ischaemia on T2 to study stroke onset time-dependency in human acute stroke lesions. Methods:Six rats were subjected to permanent middle cerebral occlusion to induce focal ischaemia, and a consecutive cohort of acute stroke patients (n=38) were recruited within 9 hours from symptom onset. T1-weighted structural, T2 relaxometry, and diffusion MRI for apparent diffusion coefficient (ADC) were acquired. Ischaemic lesions were defined as regions of lowered ADC. The median T2 difference (ΔT2) between lesion and contralateral non-ischaemic control region was determined by the newly-developed spherical reference method, and data compared to that obtained by the mirror reference method. Linear regressions and receiver operating characteristics (ROC) were compared between the two methods. Results:ΔT2 increases linearly in rat brain ischaemia by 1.9 ± 0.8 ms/h during the first 6 hours, as determined by the spherical reference method. In patients, ΔT2 linearly increases by 1.6 ± 1.4 and 1.9 ± 0.9 ms/h in the lesion, as determined by the mirror reference and spherical reference method, respectively. ROC analyses produced areas under the curve of 0.83 and 0.71 for the spherical and mirror reference methods, respectively. Conclusions:Data from the spherical reference method showed that the median T2 increase in the ischaemic lesion is correlated with stroke onset time in a rat as well as in a human patient cohort, opening the possibility of using the approach as a timing tool in clinics.

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P = .04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.

An ideal model for decision making in cancer is shared decision-making (SDM). Primary facilitators in this model are information-seeking about treatment options and patient-physician trust. Previous studies have investigated the role of each of these parameters individually. However, little is known about their convergent role in treatment decision-making. Therefore, we explored perspectives of metastatic breast cancer (MBC) patients and healthcare professionals about the influence of health information-seeking and physician trust in the SDM process. Qualitative interviews with 20 MBC patients and 6 community oncologists, as well as 3 separate focus groups involving lay navigators, nurses, and academic oncologists, were conducted, recorded, and transcribed. Qualitative data analysis employed a content analysis approach, which included a constant comparative method to generate themes from the transcribed textual data. Five emergent themes were identified (1) physicians considered themselves as the patients' primary source of treatment information; (2) patients trusted their physician's treatment recommendations; (3) patients varied in their approach to seeking further health information regarding the discussed treatment options (e.g., internet websites, family and friends, support groups); (4) other healthcare professionals were cognizant of their fundamental role in facilitating further information-seeking; and (5) patient and physician discordant perspectives on shared decision making were present. Patient procurement of treatment information and the capacity to use it effectively in conjunction with patient trust in physicians play an important role in the shared decision-making process.

Precision medicine promises to improve patient outcomes, but much is unknown about its adoption within health-care systems. A comprehensive implementation plan is needed to realize its benefits. We convened 80 stakeholders for agenda setting to inform precision medicine policy, delivery, and research. Conference proceedings were audio-recorded, transcribed, and thematically analyzed. We mapped themes representing opportunities, challenges, and implementation strategies to a logic model, and two implementation science frameworks provided context. The logic model components included inputs: precision medicine infrastructure (clinical, research, and information technology), big data (from data sources to analytics), and resources (e.g., workforce and funding); activities: precision medicine research, practice, and education; outputs: precision medicine diagnosis; outcomes: personal utility, clinical utility, and health-care utilization; and impacts: precision medicine value, equity and access, and economic indicators. Precision medicine implementation challenges include evidence gaps demonstrating precision medicine utility, an unprepared workforce, the need to improve precision medicine access and reduce variation, and uncertain impacts on health-care utilization. Opportunities include integrated health-care systems, partnerships, and data analytics to support clinical decisions. Examples of implementation strategies to promote precision medicine are: changing record systems, data warehousing techniques, centralized technical assistance, and engaging consumers. We developed a theory-based, context-specific logic model that can be used by health-care organizations to facilitate precision medicine implementation.

Cognitive dysfunction is prevalent in patients with major depressive disorder (MDD), with deficits observed across several domains (e.g., executive function, memory, attention). While depression alone is disabling, patients with cognitive deficits typically experience greater functional impairments, poorer clinical recovery, and reduced quality of life. Consequently, it is imperative to elucidate recent advances in our understanding of the treatment of cognitive dysfunction in MDD. Areas covered: This review spans psychological, physical, and pharmacological treatment approaches for cognitive dysfunction in depression. Where possible, the authors summarise where treatments have demonstrated efficacy in improving specific cognitive domains (e.g., attention), and highlight the differential mechanisms which underpin cognitive improvement. In addition, the roles of adjunctive cognitive treatments (e.g., exercise), and the possible side effects and drawbacks of specific treatments are explored. Expert opinion: Psychological treatments typically confer cognitive improvement alongside functional and/or clinical recovery; however, the efficacy of cognitive training and cognitive behavioral therapy to longitudinal cognitive improvement remains to be established. Recently developed pharmacological agents may improve cognition by reducing low-grade inflammation and promoting neurogenesis; however, the pro-cognitive effects of typical antidepressants are limited. Integrated approaches which emphasize cognitive recovery alongside clinical and functional improvement may be key to advancing patient outcomes.

Background TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. Methods In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. Results When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. Conclusions TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.

TruGraf v1 is a laboratory-developed DNA microarray-based gene expression blood test to enable proactive noninvasive serial assessment of kidney transplant recipients with stable renal function. It has been previously validated in patients identified as Transplant eXcellence (TX: stable serum creatinine, normal biopsy results, indicative of immune quiescence), and not-TX (renal dysfunction and/or rejection on biopsy results). TruGraf v1 is intended for use in subjects with stable renal function to measure the immune status as an alternative to invasive, expensive, and risky surveillance biopsies. Materials and Methods In this study, simultaneous blood tests and clinical assessments were performed in 192 patients from 7 transplant centers to evaluate TruGraf v1. The molecular testing laboratory was blinded to renal function and biopsy results. Results Overall, TruGraf v1 accuracy (concordance between TruGraf v1 result and clinical and/or histologic assessment) was 74% (142/192), and a result of TX was accurate in 116 of 125 (93%). The negative predictive value for TruGraf v1 was 90%, with a sensitivity 74% and specificity of 73%. Results did not significantly differ in patients with a biopsy-confirmed diagnosis vs those without a biopsy. Conclusions TruGraf v1 can potentially support a clinical decision enabling unnecessary surveillance biopsies with high confidence, making it an invaluable addition to the transplant physician's tool kit for managing patients. TruGraf v1 testing can potentially avoid painful and risky invasive biopsies, reduce health care costs, and enable frequent assessment of patients with stable renal function to confirm the presence of immune quiescence in the peripheral blood.

Background and objective: Multiple factors including chemical composition and microstructure influence relaxivity of tissue water in vivo. We have quantified T1 in the human white mater (WM) together with diffusion tensor imaging to study a possible relationship between water T1, diffusional fractional anisotropy (FA) and fibre-to-field angle. Methods: An inversion recovery (IR) pulse sequence with 6 inversion times for T1 and a multi-band diffusion tensor sequence with 60 diffusion sensitizing gradient directions for FA and the fibre-to-field angle θ (between the principal direction of diffusion and B0) were used at 3 Tesla in 40 healthy subjects. T1 was assessed using the method previously applied to anisotropy of coherence lifetime to provide a heuristic demonstration as a surface plot of T1 as a function of FA and the angle θ. Results: Our data show that in the WM voxels with FA > 0.3 T1 becomes longer (i.e. 1/T1 = R1 slower) when fibre-to-field angle is 50-60o, approximating the magic angle of 54.7o. The longer T1 around the magic angle was found in a number of WM tracts independent of anatomy. S0 signal intensity, computed from IR fits, mirrored that of T1 being greater in the WM voxels when the fibre-to-field angle was 50-60o. Conclusions: The current data point to fibre-to-field-angle dependent T1 relaxation in WM as an indication of effects of microstructure on the longitudinal relaxation of water.

Chinese hamster ovary (CHO) cells are the leading mammalian cell expression platform for biotherapeutic recombinant molecules yet some proteins remain difficult to express (DTE) in this, and other, systems. In recombinant cell lines expressing DTE proteins, cellular processes to restore proteostasis can be triggered when the folding and modification capabilities are exceeded, including the unfolded protein response and ER-associated degradation (ERAD) and proteasomal degradation. We therefore investigated whether the proteasome activity of CHO cells was linked to their ability to produce recombinant proteins. We found cell lines with diverse monoclonal antibody (mAb) productivity show different susceptibilities to inhibitors of proteasome activity. Subsequently, we applied selective pressure using proteasome inhibitors on mAb producing cells to determine the impact on cell growth and recombinant protein production, and to apply proteasome selective pressure above that of a metabolic selection marker during recombinant cell pool construction. The presence of proteasome inhibitors during cell pool construction expressing two different model molecules, including a DTE Fc-fusion protein, resulted in the generation of cell pools with enhanced productivity. The increased productivities, and ability to select for higher producing cells, has potential to improve clonal selection during upstream processes of DTE proteins.