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Summary: In the present study of G-6 PD status, aflatoxins and neonatal jaundice, involving, 78 jaundiced and control in-born babies and 124 jaundiced and control out-born infants, G-6 PD was deficient in more male jaundiced babies (in-and out-borns) than in the controls (P0.05), or in the controls (P>0.05). The frequency of aflatoxin detection in peripheral blood in relation to G-6-PD status and the presence or absence of jaundice.

Background: Community pharmacists are expected to uphold ethical duties to patients and society while maintaining independent businesses or fulfilling expectations of corporate owners. Canadian pharmacy colleges provide only indirect guidance on the retail setting of the profession. Little is known about whether pharmacists identify ethical issues in retail pharmacy or around the sales of non-drug products. Objective: This study sought to examine pharmacists' perceptions of their roles in health promotion, the factors that influence the selection of front-of-store products, and ethical issues relating to their dual roles as health care providers and retailers. Methods: In 2020, 25 Canadian pharmacists participated in semi-structured phone interviews. Interviews were audio-recorded, anonymized, transcribed verbatim, and thematically analyzed using qualitative methods. Results: Almost all participants described their role primarily as a health care provider, though some described themselves as 50–50 health care providers and retailers. Most staff pharmacists reported little control over front-of-store product selection. Where participants reported some control, external factors such as business viability and profitability impacted their choices, though some reported selecting products based on the needs of their patient community or their personal beliefs. The dominant tensions described stemmed from participants' dual roles as health care providers and retailers, though specific issues and situations were varied, ranging corporate targets, to service provision, to the sales of unproven or unhealthy products. Participants suggested solutions to the issues they described, ranging from a complete overhaul of the licensing structure of community pharmacies, down to one-on-one conversations with patients. Conclusion: Our findings suggest that the retail setting of community pharmacy produces unique ethical tensions: the imposition of retail sales standards and targets are commonplace, and business viability is a primary driving force in front-of-store product selection. Clear guidance from Canadian pharmacy colleges and legislators to address these tensions and issues may be necessary.

IntroductionThe COVID-19 pandemic prompted a surge in digital public health surveillance worldwide, with limited opportunities to consider the effectiveness or impact of digital surveillance. The news media shape public understanding of topics of importance, contributing to our perception of priority issues. This study investigated news media reports published during the first year of the pandemic to understand how the use and consequences of digital surveillance technologies were reported on.MethodsA media content analysis of 34 high- to low-income countries was completed. The terms “COVID-19,” “surveillance,” “technologies,” and “public health” were used to retrieve and inductively code media reports.ResultsOf the 1,001 reports, most were web-based or newspaper sources on the development and deployment of technologies directed at contact tracing, enforcing quarantine, predicting disease spread, and allocating resources. Technology types included mobile apps, wearable devices, “smart” thermometers, GPS/Bluetooth, facial recognition, and security cameras. Repurposed data from social media, travel cards/passports, and consumer purchases also provided surveillance insight. Media reports focused on factors impacting surveillance success (public participation and data validity) and the emerging consequences of digital surveillance on human rights, function creep, data security, and trust.DiscussionDiverse digital technologies were developed and used for public health surveillance during the first year of the COVID-19 pandemic. The use of these technologies and witnessed or anticipated consequences were reported by a variety of media sources worldwide. The news media are an important public health information resource, as media outlets contribute to directing public understanding and shaping priority public health surveillance issues. Our findings raise important questions around how journalists decide which aspects of public health crises to report on and how these issues are discussed.

No abstract available. Article truncated after 150 words. A 58-year-old woman with a history of orthotopic heart transplant, performed for Adriamycin-induced cardiomyopathy, treated with mycophenolate and tacrolimus, presented for routine interval follow up. The patient’s past medical history was significant for follicular thyroid carcinoma treated with total thyroidectomy and bilateral breast carcinoma in remission as well as hypothyroidism and type II diabetes mellitus. In addition to tacrolimus and mycophenolate, the patient’s medications included aspirin, insulin, itraconazole (for anti-fungal prophylaxis), levothyroxine, prednisone (tapering since transplant), and valganciclovir. The patient recently complained of rhinorrhea and cough productive of brown-tinged sputum, improving over the previous 2 weeks; she denied fever, chills, shortness of breath, night sweats chest pain, or gastrointestinal symptoms. Physical examination showed the patient to be afebrile with normal heart and respiratory rates and blood pressure. Her room air oxygen saturation was 99%. The patient’s complete blood count and serum chemistries showed largely normal values, with the white blood …

Abstract Background Eosinophilic lung diseases represent a heterogeneous group of disorders with prominent infiltrate of eosinophils in lung interstitium and alveolar spaces. Peripheral blood eosinophilia is often present. Infections, drugs, allergens, toxic agents have to be evaluated as possible causes of eosinophilic lung infiltrates. The category of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2 represents an uncommon cause of eosinophilic lung infiltrate. Case presentation We report the case of a 70-year old man complaining of dry cough and dyspnea. Ground glass-opacities were seen on imaging studies and peripheral blood eosinophilia was present. A thorough step-wise patient’s evaluation led to identify the clonal nature of eosinophilia and the diagnosis of myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA was made. Conclusions Correlation with clinical history, laboratory tests and imaging studies is essential to achieve the correct diagnosis when facing with eosinophilic lung infiltrates. A prolonged eosinophilia can cause life-threatening organ damage. Identification of PDGFRA rearrangement, as in the present case, is particularly critical given the sensitivity and excellent response to imatinib, which has completely changed the natural history of this neoplasm.

We finally have a vaccine for the COVID-19 crisis. However, due to the limited numbers of the vaccine, states will have to consider how to prioritise groups who receive the vaccine. In this paper, we argue that the practical implementation of human rights law requires broader consideration of intersectional needs in society and the disproportionate impact that COVID-19 is having on population groups with pre-existing social and medical vulnerabilities. The existing frameworks/mechanisms and proposals for COVID-19 vaccine allocation have shortcomings from a human rights perspective that could be remedied by adopting an intersectional allocative approach. This necessitates that states allocate the first COVID-19 vaccines according to (1) infection risk and severity of pre-existing diseases; (2) social vulnerabilities; and (3) potential financial and social effects of ill health. In line with WHO’s guidelines on universal health coverage, a COVID-19 vaccine allocation strategy that it is more consistent with international human rights law should ensure that vaccines are free at the point of service, give priority to the worst off and be allocated in a transparent, participatory and accountable prioritisation process.

Drug regulatory bodies aim to ensure that patients have access to safe and effective drugs; however, no matter the quality of pre-licensure studies, uncertainty will remain regarding the safety and effectiveness of newly approved drugs until a large and diverse population uses those drugs. Recent analyses of Canada’s post-market drug surveillance (PMDS) system have found that Canada is not keeping pace with international requirements for PMDS, and have noted that efforts must be improved to monitor and address the safety and effectiveness of approved drugs among vulnerable populations. Given the uncertainty that exists when drugs enter the market, some have suggested that the precautionary principle is relevant to guiding decision-making in this context. This paper responds to recommendations that the Canadian PMDS system should be responsive to the health needs of vulnerable populations by assessing the utility of deploying the precautionary principle to guide a post-market strategy for vulnerable populations.

The nursing shortage, coupled with growing case loads, limits the available time for nurses in home care to attend continuing professional education programs necessary to keep abreast of the changes in nursing practice and enhance their clinical competency. The purpose of this case study was to evaluate the effectiveness of the WebQuest, a Web-based inquiry-oriented model congruent with the pedagogical approaches and cognitive activities commonly used with nursing education, in providing continuing education content to nurses in a mid-sized home health care agency. A convenience sample of registered nurse case managers completed a researcher-designed WebQuest, modified for independent learning, on diabetes education utilizing their personal computers from home. WebQuests proved to be an innovative and creative approach to provide new information, promote higher level thinking skills, and develop nurses' confidence with computer technology. [ABSTRACT FROM AUTHOR]

Objective: To investigate feeding practices in infants under the age of 4 months in Liverpool, England with particular reference to the cost of infant feeding.Design: A cross-sectional survey consisting of self-completion questionnaires and interviews.Setting: Subjects' homes within Central and South Liverpool Primary Care Trust areas.Subjects: One hundred and forty-nine women (aged 18 to 43 years) and their infants (mean age 13 weeks).Results: The average weekly cost of breast-feeding was 11.58 pounds sterling compared with 9.60 pounds sterling for formula-feeding. Many breast- and formula-feeding women spent money however on items that were not needed or used only once or twice. This was especially true of first-time mothers. Characteristics significantly associated with higher spending were: feeding method - mothers that had or were partially breast-feeding (P=0.001), education - those educated to degree level (P=0.028), socio-economic status - those in social classes I and II (P=0.002) and age - those aged 30 years and over (P=0.003).Conclusions: This study demonstrates that while breast-feeding is often promoted as being free, this is not the case. Better information needs to be given to parents to avoid wasting money on items that are unnecessary, or where cheaper alternatives are available. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to investigate whether a subject's level of satiety influences perception of their usual portion size. METHODS: A total of 62 school children were recruited for the pilot study. Half of the group assessed food photographs for their usual portion size before lunch, and half after lunch. For the main study, 55 female students were recruited to test within-subject variation in perception of usual portion size before and after consuming a preload. RESULTS: Significant differences in perception of portion size were found for four of the six foods used. CONCLUSION: Some subjects' perception of their usual portion size was influenced by their level of satiety. Further study is needed to investigate this using a wider variety of food photographs and an alternative preload. [ABSTRACT FROM AUTHOR]

BACKGROUND: Food Photographs and standard portion sizes have been used with adults to assess portion size when recording dietary intake. The effectiveness of these methods may be reduced when memory/recall is required and children may have problems using these techniques. METHODS: Adults (47) and children (37) were recruited from amongst university personnel, their children and children's friends to assess portion sizes of nine self-served amounts of selected food items using food photographs and standard descriptions of portion sizes. Portion sizes were estimated directly after self-serving and three - 4 days later. RESULTS: Substantial differences in the estimate of portion sizes were observed for most foods regardless of the method used or the age of the subjects, median difference range: -52-100%. For children there were greater errors using both methods than for adults. Significant differences were found between the two methods of estimating weight. The food atlas provided higher median estimated weights for the majority of the food items. There were very few differences in the estimation of portion sizes between the two testing periods. CONCLUSION: The findings would suggest that either an alternative method or a modification of the methods used here for estimating portion sizes in young subjects, for example standard food portion sizes for children of different ages such as those that are being developed by the Food Standards Agency, would be more appropriate. [ABSTRACT FROM AUTHOR]

AIM: It is the intention of this study establish the extent of dieting practices amongst adolescent girls and identify their perceptions with regard to 'dieting' and 'healthy eating'. METHODS: A total of 140 girls, aged 12-13 years, were recruited from two schools. A self-reported questionnaire, which determined the incidence of dieting and sought to identify the girls' perceptions of 'dieting' and 'healthy eating', was used to collect data. RESULTS: Out of the total group, 33.6% reported that they had dieted at some time and 15.8% were presently dieting. The most popular definition of dieting amongst the dieters was 'eating less/cutting down'; however, the second most popular answer was 'eating healthy food' which was the most popular answer amongst the non-dieters. The most popular definition of healthy eating was 'increasing fruit/ veg/salads', which is similar to how many girls perceived dieting, i.e. eating healthy food (fruit/veg/salads). CONCLUSION: Establishing the actual incidence of dieting amongst adolescent girls is not a clear-cut issue as it can be interpreted in many different ways, depending on the perceptions of the individual. The results of this study showed that in many cases 'dieting' and 'healthy eating' were perceived in a similar light, concluding that the dietary intake of dieters may be similar to that of non-dieters with both groups being at risk from any related health problems. [ABSTRACT FROM AUTHOR]

Millions of Americans regularly use herbal supplements, but many are unaware of the potential hidden dangers. Numerous supplements have been associated with hepatotoxicity and, indeed dietary/herbal supplements represent an increasingly common source of acute liver injury. We report a case of acute liver failure requiring liver transplantation associated with the use of Garcinia cambogia, a supplement widely promoted for weight loss. When patients present with acute hepatitis or liver failure from an unknown etiology, a careful history of supplement use should be performed.

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described. Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients. Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08–10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23–13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1–34.6, p = 0.04). Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.

Background A large percentage of Liverpool Somalis have vitamin D deficiency and low calcium excretion. The dietary habits of Liverpool Somalis were investigated with respect to food items containing calcium and vitamin D. Methods A questionnaire, administered by a Somali field worker, assessed the intake of food of 60 adult (45 females and 15 males; mean age 42 years) and 10 child (seven females and three males; mean age 10 years) Somali volunteers. Questions concerned personal details, health (bone and muscle problems) and dietary habits including the frequency of consumption of food items containing substantial amounts of calcium and vitamin D. Results Most subjects reported bone and muscle pain. Eating habits reflected traditional customs. Foods containing substantial amounts of calcium and vitamin D were consumed infrequently. Milk was only consumed in tea. Those self-reporting bone pain consumed eggs, cheese and beans rarely. Conclusion The food choices of these individuals with regard to bone health is a cause for concern and indicates a likelihood of low calcium and vitamin D intake. [ABSTRACT FROM AUTHOR]

A single-column radiative-convective model (RCM) is a useful tool to investigate the physical processes that determine the tropical tropopause layer (TTL) temperature structures. Previous studies on the TTL using the RCMs, however, omitted the cloud radiative effects. In this study, we examine the impact of cloud radiative effects on the simulated TTL temperatures using an RCM. We derive the cloud radiative effects based on satellite observations, which show heating rates in the troposphere but cooling rates in the stratosphere. We find that the cloud radiative effect warms the TTL by as much as 2 K but cools the lower stratosphere by as much as −1.5 K, resulting in a thicker TTL. With (without) considering cloud radiative effects, we obtain a convection top of ≈167 hPa (≈150 hPa) with a temperature of ≈213 K (≈209 K), and a cold point at ≈87 hPa (≈94 hPa) with a temperature of ≈204 K (≈204 K). Therefore, the cloud radiative effects widen the TTL by both lowering the convection-top height and enhancing the cold-point height. We also examine the impact of TTL cirrus radiative effects on the RCM-simulated temperatures. We find that the TTL cirrus warms the TTL with a maximum temperature increase of ≈1.3 K near 110 hPa.

Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (approximately 70-80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses. Here, we demonstrate that galectin-9, the natural ligand for the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), circulates at very high levels in the serum and its hepatic expression (particularly on Kupffer cells) is significantly increased in patients with chronic HCV as compared to normal controls. Galectin-9 production from monocytes and macrophages is induced by IFN-gamma, which has been shown to be elevated in chronic HCV infection. In turn, galectin-9 induces pro-inflammatory cytokines in liver-derived and peripheral mononuclear cells; galectin-9 also induces anti-inflammatory cytokines from peripheral but not hepatic mononuclear cells. Galectin-9 results in expansion of CD4(+)CD25(+)FoxP3(+)CD127(low) regulatory T cells, contraction of CD4(+) effector T cells, and apoptosis of HCV-specific CTLs. In conclusion, galectin-9 production by Kupffer cells links the innate and adaptive immune response, providing a potential novel immunotherapeutic target in this common viral infection.

Nesting colonial seabirds are prime examples of central-place foragers, animals that must return to a central location (e.g., a breeding colony) after each bout of foraging. They must balance the costs and benefits of foraging with the need to return to their colonies frequently to form pair bonds during courtship, incubate, provision mates and offspring, and protect and rear young. For some populations, the loss and degradation of suitable breeding habitat due to human activities have necessitated the construction of new breeding sites and/or the restoration of previously occupied sites. South Island, which is part of the Hampton Roads Bridge-Tunnel (HRBT) complex in the Commonwealth of Virginia, U.S.A., is a human-created island that supported Virginia's largest mixed species seabird colony until 2020, when the expansion of the HRBT began and when all nesting seabirds were permanently excluded from the site. We studied the movement patterns of foraging common terns (Sterna hirundo) to determine how travel to and around foraging sites related to their colony location and to inform the siting and construction of a new breeding island. We tracked 18 individual common terns from 07 June to 29 June 2018, and we used a hidden Markov model to assign behavioral states and investigate common tern movements around the HRBT. Common terns spent more than half their time in the colony (58%), followed by time devoted to foraging (22%), and the remainder of their time was spent on outbound (15%) and inbound (5%) transit. Terns traveled as far as 98km from the colony, but on average foraged relatively close to South Island (13.6 ± 0.3km, mean ± 1 SD). Individuals tended to forage in the same locations, but there was variation among individuals. Flying to foraging sites uses energy during the already energetically costly breeding season, thus managers should prioritize placing a new colony site in a location that minimizes the distance traveled to the foraging locations frequented by the South Island birds while accounting for other life-history characteristics. These findings could help in the design and construction of new breeding sites or the restoration of current sites for other, related species, particularly for which these data do not exist., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Catlin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Code of Ethics and Professional Standards of Conduct for Emergency Management Professionals (2022) was recently created to further delineate the ethical boundaries and conduct expectations for professional emergency management practice. Significantly, the code of ethics provides an essential foundation toward recognition as a profession with hallmarks of monopoly, autonomy, and authority. The code and standards of conduct establish a clear definition of the role emergency management has in overseeing a complex, diverse risk portfolio that protects lives, livelihoods, and quality of life. The document captures the intent, challenges, dimensions, and significance of emergency management practice in a rapidly changing world and brings ethics to the forefront of decisions. This article speaks to the discursive dialogue toward, methodological development of, and future tools for integrating into practice the Code of Ethics and Professional Standards of Conduct for Emergency Management Professionals.

Adolescent bullying victimization is recognized as a public health and mental health problem in many countries. However, data on bullying victimization's prevalence and risk factors is scarce in sub-Saharan Africa Sierra Leone. This research aimed to determine bullying victimization prevalence and its associated factors among Sierra Leonean school-going adolescents. The Sierra Leone 2017 Global School-based Health Survey (GSHS) dataset was analyzed. The outcome variable was the respondent's self-report of bullying victimization ("How many days in the previous 30 days were you bullied?"). Descriptive, Pearson chi-square and binary logistic regression analyses were conducted. The regression analysis yielded adjusted odds ratios (aOR) with 95% confidence intervals (CIs) and a significance level of p 0.05. Bullying victimization was prevalent among 48.7% of the in-school adolescents. Adolescents who drank alcohol [aOR = 2.48, 95% CI = 1.50-4.10], who reported feelings of loneliness [aOR = 1.51, 95% CI = 1.07-2.14] and who had attempted suicide [aOR = 1.72, 95% CI = 1.03-2.87] were also more likely to be bullied. Also, school truancy [aOR = 1.53, 95% CI = 1.24-1.88] among teenagers was associated with an increased risk of being bullied. Our findings suggest that bullying is a widespread problem among Sierra Leonean school-aged youth, and alcohol drinking, loneliness, suicide attempt and school truancy are potential risk factors. In light of the aforementioned causes of bullying in schools, policymakers and school administrators in Sierra Leone need to develop and execute anti-bullying policies and initiatives that target the underlying risk factors of bullying among teenagers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Osborne et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Climate change is one of the top three global threats to seabirds, particularly species that visit polar regions. Arctic terns migrate between both polar regions annually and rely on productive marine areas to forage, on sea ice for rest and foraging, and prevailing winds during flight. Here, we report 21st-century trends in environmental variables affecting arctic terns at key locations along their Atlantic/Indian Ocean migratory flyway during the non-breeding seasons, identified through tracking data. End-of-century climate change projections were derived from Earth System Models and multi-model means calculated in two Shared Socioeconomic Pathways: 'middle-of-the-road' and 'fossil-fuelled development' scenarios. Declines in North Atlantic primary production emerge as a major impact to arctic terns likely to affect their foraging during the 21st century under a 'fossil-fuelled development' scenario. Minimal changes are, however, projected at three other key regions visited by arctic terns (Benguela Upwelling, Subantarctic Indian Ocean and the Southern Ocean). Southern Ocean sea ice extent is likely to decline, but the magnitude of change and potential impacts on tern survival are uncertain. Small changes (<1 m s -1 ) in winds are projected in both scenarios, but with minimal likely impacts on migration routes and duration. However, Southern Ocean westerlies are likely to strengthen and contract closer to the continent, which may require arctic terns to shift routes or flight strategies. Overall, we find minor effects of climate change on the migration of arctic terns, with the exception of poorer foraging in the North Atlantic. However, given that arctic terns travel over huge spatial scales and live for decades, they integrate minor changes in conditions along their migration routes such that the sum effect may be greater than the parts. Meeting carbon emission targets is vital to slow these end-of-century climatic changes and minimise extinction risk for a suite of polar species., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Background: Several disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) reduce relapse rates and slow disease progression. RRMS DMTs have varying efficacy and administration routes; DMTs prescribed first may not be the most effective on relapses or disease progression. Here, we aimed to quantify the benefit of initiating ofatumumab, a high-efficacy DMT, earlier in the treatment pathway., Methods: Aggregate data from a real-world cohort of patients with RRMS, who were eligible for dimethyl fumarate (DMF) or ofatumumab treatment within the UK National Health Service ( N  = 615), were used to produce a simulated patient cohort. The cohort was tracked through a discrete event simulation (DES) model, based on the Expanded Disability Status Scale (EDSS), with a lifetime time horizon. Outcomes assessed were: mean number of relapses, time to wheelchair (EDSS ≥7), and time to death. Two modeling approaches were used. The first compared outcomes between two treatment sequences (base case: ofatumumab to natalizumab versus DMF to ofatumumab). The second incorporated a time-specific delay of 1-5 years for switching from DMF to ofatumumab; the difference in outcomes as a function of increasing delay to ofatumumab are reported., Results: Compared with delayed ofatumumab, fewer relapses and increased time to wheelchair were predicted for earlier ofatumumab in the treatment-sequence approach (mean relapses over the lifetime time horizon: 8.63 versus 9.00; time to wheelchair: 17.55 versus 16.60 years). Time to death was similar for both sequences. At Year 10, a numerically greater proportion of patients receiving earlier ofatumumab had mild disease (EDSS 0-3: 44.12% versus 40.06%). Greater differences, reflecting poorer outcomes, were predicted for relapses and time to wheelchair with increasing delays to ofatumumab treatment., Conclusions: The DES model provided a means by which the magnitude of benefit associated with earlier ofatumumab initiation could be quantified; fewer relapses and a prolonged time to wheelchair were predicted.

Introduction: Fluorouracil (5-FU) pharmacokinetics are variable, leading to a risk of toxicity in some patients and underdosing in others. Therapeutic drug monitoring of 5-FU was shown to reduce toxicity and increase efficacy. This study assessed the clinical utility of starting treatment with 70-80% of BSA calculated dose and titrating according to 5-FU blood levels and toxicity., Methods: A retrospective analysis of a prospectively collected database of 126 patients treated with regimens containing 5-FU bolus and continuous infusion for 46 h for whom the 5-FU blood level was collected at least once. Response,and date of progression, and death were collected for patients with colon and pancreatic cancer., Results: In multivariate analysis, 5-FU blood levels were correlated with 5-FU dose and with age, albeit a small effect size (coefficient = 0.007). Of patients with colon cancer treated with an initial lower 5-FU dose, 18% had a therapeutic 5-FU blood level. The median survival was similar in patients with metastatic colon cancer treated with lower doses and those treated with a full dose. Of patients with pancreatic cancer treated with lower doses, 40% had therapeutic blood levels. The median survival was 13 months in patients with metastatic pancreatic cancer treated with lower 5-FU doses., Conclusion: Starting treatment with low 5-FU dose was associated with patient survival comparable to other published data, and a sizeable percentage of patients had therapeutic blood levels. This approach can be considered, especially in elderly and frail patients., (© 2022 S. Karger AG, Basel.)

Embryos are diagnosed as mosaic if their chromosomal copy number falls between euploid and aneuploid. The purpose of this study was to investigate the impact of mosaicism on global gene expression. This study included 42 blastocysts that underwent preimplantation genetic testing for aneuploidy (PGT-A) and were donated for IRB approved research. Fourteen blastocysts were diagnosed as mosaic with Next-generation Sequencing (NGS). Three NGS diagnosed euploid embryos, and 25 aneuploid embryos (9 NGS, 14 array Comparative Genomic Hybridization, 2 Single Nucleotide Polymorphism array) were used as comparisons. RNA-sequencing was performed on all of the blastocysts. Differentially expressed genes (DEGs) were calculated using DESeq2/3.5 (R Bioconductor Package) with p < 0.05 considered significantly differentially expressed. Pathway analysis was performed on mosaic embryos using EnrichR with p < 0.05 considered significant. With euploid embryo gene expression used as a control, 12 of 14 mosaic embryos had fewer DEGs compared to aneuploid embryos involving the same chromosome. On principal component analysis (PCA), mosaic embryos mapped separately from aneuploid embryos. Pathways involving cell proliferation, differentiation, and apoptosis were the most disrupted within mosaic embryos. Mosaic embryos have decreased disruption of global gene expression compared to aneuploid embryos. This study was limited by the small sample size, lack of replicate samples for each mosaic abnormality, and use of multiple different PGT-A platforms for the diagnosis of aneuploid embryos., (© 2022. Society for Reproductive Investigation.)

Background: Women with infertility and heart disease (HD) are increasingly seeking assisted reproductive technology (ART). There is only one other study that examines the safety profile of ART in this population. This study aims to evaluate the cardiac, reproductive, and obstetric outcomes of ART in women with HD., Methods: We conducted a retrospective case-control study of women with underlying congenital or acquired HD who underwent ART at a single University fertility center from 1/2010-3/2019. Women undergoing in-vitro fertilization (IVF), oocyte cryopreservation (OC) or embryo banking (EB) with HD were included. Cases were matched 3:1 with age-, cycle type- and cycle start date- matched controls without HD. Outcomes included cardiovascular (CV), reproductive, and obstetric complications during or following ART., Results: Twenty women with HD were included. 15 (75%) had congenital HD, 1 (5%) had valvular disease, 1 (5%) had acquired cardiomyopathy, and 3 (15%) had arrhythmias. 90% were New York Heart Association class I. 55% of HD cases were modified WHO (mWHO) risk classification 1-2, 40% were mWHO 2-3 or 3, 5% were mWHO 4. Cases underwent 25 IVF, 5 OC, and 5 EB cycles and were compared with 79 controls who underwent 174 cycles. No CV complications or deaths occurred amongst cases following ART or pregnancy. There was no difference in risk of ART or obstetric outcomes amongst cases versus controls., Conclusion: For women with HD in this small, low -risk cohort, ART posed few risks that were similar in frequency to healthy controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quien, Hausvater, Maxwell and Weinberg.)

Offshore wind energy is expanding globally and new floating wind turbine technology now allows wind energy developments in areas previously too deep for fixed-platform turbines. Floating offshore wind has the potential to greatly expand our renewable energy portfolio, but with rapid expansion planned globally, concerns exist regarding impacts to marine species and habitats. Floating turbines currently exist in three countries but large-scale and rapid expansion is planned in over a dozen. This technology comes with unique potential ecological impacts. Here, we outline the various floating wind turbine configurations, and consider the potential impacts on marine mammals, seabirds, fishes and benthic ecosystems. We focus on the unique risks floating turbines may pose with respect to: primary and secondary entanglement of marine life in debris ensnared on mooring lines used to stabilize floating turbines or dynamic inter-array cables; behavioral modification and displacement, such as seabird attraction to perching opportunities; turbine and vessel collision; and benthic habitat degradation from turbine infrastructure, for example from scour from anchors and inter-array cables. We highlight mitigation techniques that can be applied by managers or mandated through policy, such as entanglement deterrents or the use of cable and mooring line monitoring technologies to monitor for and reduce entanglement potential, or smart siting to reduce impacts to critical habitats. We recommend turbine configurations that are likely to have the lower ecological impacts, particularly taut or semi-taut mooring configurations, and we recommend studies and technologies still needed that will allow for floating turbines to be applied with limited ecological impacts, for example entanglement monitoring and deterrent technologies. Our review underscores additional research and mitigation techniques are required for floating technology, beyond those needed for pile-driven offshore or inshore turbines, and that understanding and mitigating the unique impacts from this technology is critical to sustainability of marine ecosystems., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: Transition to secondary progressive multiple sclerosis (SPMS) from relapsing-remitting MS (RRMS) is an expected part of the disease trajectory for most patients. However, the transition is challenging to identify due to the gradual nature of progression, and the complications of superimposed relapses, comorbidities, and natural variability in symptoms. This healthcare professional (HCP) survey sought to characterize the transition to and management of SPMS in UK clinical practice., Methods: Telephone interviews with 20 neurologists and MS specialist nurses from England and Scotland gathered quantitative and qualitative responses. Numerical analyses and theoretical thematic methods were used to identify key emerging themes., Results: The burden SPMS imposes on patients and caregivers was a major theme; discharge from specialist services is common, leading to a sense of abandonment. Respondents acknowledged substantial hesitancy toward identifying SPMS, predominantly due to restricted options of licensed and reimbursed disease-modifying therapies (DMTs) for SPMS compared with RRMS. Currently, HCPs continue DMTs under a label of RRMS, even after recognition of progression. This survey identified MS to be unusual in comparison with other disease areas in that reimbursement guidelines have a direct impact on clinicians' decisions around disease staging. Respondents suggested reimbursed DMTs proven to slow disability progression in SPMS will create a step-change in identifying SPMS, providing rationale to acknowledge progression earlier while removing key obstacles to identification. To aid this change, respondents identified a need for SPMS-specific diagnostic guidance, despite substantial divergence in implementation of current guidance., Conclusions: In contrast to the current heterogeneity, a more structured and standardized approach to the identification of SPMS, along with guidelines on treatment, will ensure patients can maximally benefit as treatment options for SPMS evolve., Competing Interests: Stephen Maxwell Montgomery and Fern Amy Woodhouse are employees of Costello Medical, who were contracted by Novartis Pharmaceuticals UK to undertake the work. Sophie Clare Laura Caseby was also an employee of Costello Medical at the time of the study. Michel Anton Kroes is an employee of Novartis Pharmaceuticals UK and a Novartis shareholder. Martin Edward Duddy has received honoraria for advisory boards, speaker's fees, research funding, and expenses to attend educational events from Novartis, Biogen, Celgene/Bristol‐Myers Squibb, Merck Sharp & Dohme, Roche, Sanofi Genzyme, and TG Therapeutics., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Purpose: Improving access to care is an issue at the forefront of reproductive medicine. We sought to describe how one academic center, set in the background of a large and diverse metropolitan city, cares for patients with extremely limited access to reproductive specialists., Methods: The NYU Reproductive Endocrinology and Infertility (REI) Fellowship program provides a "fellow-run clinic" within Manhattan's Bellevue Hospital Center, which is led by the REI fellows and supervised by the REI attendings of the NYU Langone Health system. A description of the history of the hospital as well as the logistics of the fertility clinic is provided as a logistical template for implementation., Results: The fellow-run fertility clinic at Bellevue hospital is held on two half days per month seeing approximately 150 new patients per year. The fertility workup, counseling, surgery, as well as ovulation induction, and early pregnancy management are offered within the construct of the fellowship and residency at NYU. Barriers to care and ways to circumvent those barriers are discussed in detail., Conclusion: By utilizing the ambition and construct of the OB/GYN programs, we greatly improve care for an otherwise underserved patient population by offering an efficient and optimal infertility workup and treatment in a population that would otherwise be without care. We utilize the framework of graduate medical education to provide autonomy, experience, and mentorship to both residents and fellows in our programs in an effort to provide a solution to combating inequity in infertility care.

It is well accepted that cancers co-opt the microenvironment for their growth. However, the molecular mechanisms that underlie cancer-microenvironment interactions are still poorly defined. Here, we show that Rho-associated kinase (ROCK) in the mammary tumour epithelium selectively actuates protein-kinase-R-like endoplasmic reticulum kinase (PERK), causing the recruitment and persistent education of tumour-promoting cancer-associated fibroblasts (CAFs), which are part of the cancer microenvironment. An analysis of tumours from patients and mice reveals that cysteine-rich with EGF-like domains 2 (CRELD2) is the paracrine factor that underlies PERK-mediated CAF education downstream of ROCK. We find that CRELD2 is regulated by PERK-regulated ATF4, and depleting CRELD2 suppressed tumour progression, demonstrating that the paracrine ROCK-PERK-ATF4-CRELD2 axis promotes the progression of breast cancer, with implications for cancer therapy.

Species distribution models (SDMs) are important management tools for highly mobile marine species because they provide spatially and temporally explicit information on animal distribution. Two prevalent modeling frameworks used to develop SDMs for marine species are generalized additive models (GAMs) and boosted regression trees (BRTs), but comparative studies have rarely been conducted; most rely on presence-only data; and few have explored how features such as species distribution characteristics affect model performance. Since the majority of marine species BRTs have been used to predict habitat suitability, we first compared BRTs to GAMs that used presence/absence as the response variable. We then compared results from these habitat suitability models to GAMs that predict species density (animals per km 2 ) because density models built with a subset of the data used here have previously received extensive validation. We compared both the explanatory power (i.e., model goodness of fit) and predictive power (i.e., performance on a novel dataset) of the GAMs and BRTs for a taxonomically diverse suite of cetacean species using a robust set of systematic survey data (1991-2014) within the California Current Ecosystem. Both BRTs and GAMs were successful at describing overall distribution patterns throughout the study area for the majority of species considered, but when predicting on novel data, the density GAMs exhibited substantially greater predictive power than both the presence/absence GAMs and BRTs, likely due to both the different response variables and fitting algorithms. Our results provide an improved understanding of some of the strengths and limitations of models developed using these two methods. These results can be used by modelers developing SDMs and resource managers tasked with the spatial management of marine species to determine the best modeling technique for their question of interest., Competing Interests: None declared., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

We investigated clinical error rates with single thawed euploid embryo transfer (STEET) diagnosed by next generation sequencing (NGS) and array comparative genomic hybridization (aCGH). A total of 1997 STEET cycles after IVF with preimplantation genetic testing for aneuploidy (PGT-A) from 2010 to 2017 were identified; 1151 STEET cycles utilized NGS, and 846 STEET cycles utilized aCGH. Any abortions, spontaneous or elective, in which products of conception (POCs) were collected were reviewed. Discrepancies between chorionic villus sampling, amniocentesis, or live birth results and PGT-A diagnosis were also included. Primary outcomes were clinical error rate per: ET, pregnancy with gestational sac, live birth, and spontaneous abortion with POCs available for analysis. Secondary outcomes included implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate (OPR/LBR). The clinical error rates in the NGS cohort were: 0.7% per embryo, 1% per pregnancy with gestational sac, and 0.1% rate per OP/LB. The error rate per SAB with POCs was 13.3%. The IR was 69.1%, the OPR/LBR was 61.6%, and the spontaneous abortion rate was 10.2%. The clinical error rates in the aCGH cohort were: 1.3% per embryo, 2% per pregnancy with gestational sac, and 0.4% rate per OP/LB. The error rate per SAB with POCs was 23.3%. The IR was 63.8%, the OPR/LBR was 54.6%, and the SAB rate was 12.4%. Our findings demonstrate that, although NGS and aCGH are sensitive platforms for PGT-A, errors still occur. Appropriate patient counseling and routine prenatal screening are recommended for all patients undergoing IVF/PGT-A., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Yes-associated protein (YAP) is known to promote the stemness of multiple stem cell types, including pluripotent stem cells, while also antagonizing pluripotency during early embryogenesis. How YAP accomplishes these distinct functions remains unclear. Here, we report that, depending on the specific cells in which it is expressed, YAP could exhibit opposing effects on pluripotency induction from mouse somatic cells. Specifically, YAP inhibits pluripotency induction cell-autonomously but promotes it non-cell-autonomously. For its non-cell-autonomous role, YAP alters the expression of many secreted and matricellular proteins, including CYR61. YAP's non-cell-autonomous promoting effect could be recapitulated by recombinant CYR61 and abrogated by CYR61 depletion. Thus, we define a YAP-driven effect on enhancing pluripotency induction largely mediated by CYR61. Our work highlights the importance of considering the distinct contributions from heterologous cell types in deciphering cell fate control mechanisms and calls for careful re-examination of the co-existing bystander cells in complex cultures and tissues., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)