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Abstract Most current Data Center Interconnects (DCI) use intensity modulation direct detection (IMDD) configurations due to their low complexity and cost. However, significant scaling challenges allow coherent solutions to become contenders in these short reach applications. We present an O-band coherent optical fiber transmission system based on Quantum Dot—Mode Locked Lasers (QD-MLLs) using two independent free-running comb lasers, one each for the carrier and the Local Oscillator (LO). Using a comb-to-comb configuration, we demonstrate a 10 km single mode fiber, O-band, coherent, heterodyne, 12.1 Tbps system operating at 0.47 Tbps/λ using 26 λs. We used fewer comb lines (26 λs), faster symbol rate (56 GBaud) and higher constellation cardinality (32 QAM) relative to the highest capacity C-band systems reported to date. Through design, analysis, and experimentation, we quantify the optimum comb line spacing for this use case. We compare potential configurations for increasing data center interconnect capacities whilst reducing power consumption, complexity, and cost.

Background. Limited data are available on the clinical profile and disease burden of hereditary angioedema (HAE) in Canadians. Objective. This study aimed to assess HAE disease characteristics and the burden of disease in Canadians with HAE types I, II, and normal levels of C1 inhibitor (nC1-INH). Materials and Methods. A 46-item patient survey evaluating clinical characteristics and burden of disease was developed and disseminated by the HAE patient organization Angio-oédeme héréditaire du Québec in Quebec, Canada, from May 2019 to February 2020. The survey received Research Review Board ethics approval. Results. In the 35 respondents, HAE type I was the most common (46%), followed by nC1-INH (43%). Female participants were significantly younger at first symptom presentation than males (p=0.04). Prior to diagnosis, 69% of participants underwent unnecessary treatments and procedures, with a 10-year delay between first symptoms and diagnosis. Before starting the current treatment, 42% of participants experienced weekly HAE attacks. Most participants identified experiencing attacks in the abdomen (89%), followed by the larynx (66%), feet (66%), hands (63%), and face (63%). Most attacks were severe or moderate, yet almost half of patients waited >1 hr before getting medical attention at their last emergency department (ED) visit. HAE was associated with decreased health-related quality of life, leading to significant functional impairment in personal and professional life. As compared to HAE type I/II, patients with HAE nC1-INH were treated more often with tranexamic acid for long-term prophylaxis, and their condition was less controlled, resulting in more attacks and ED visits. Conclusion. HAE manifests in this patient population as frequent moderate-to-severe attacks and a high disease burden; the HAE subtype may differentially affect care requirements. There is an urgent need for increased awareness and education on HAE among treating physicians.

Abstract Background In randomized clinical controlled trials, the choice of usual care as the comparator may be associated with better clinician uptake of the study protocol and lead to more generalizable results. However, if care processes evolve to resemble the intervention during the course of a trial, differences between the intervention group and usual care control group may narrow. We evaluated the effect on mean arterial pressure of an unblinded trial comparing a lower mean arterial pressure target to reduce vasopressor exposure, vs. a clinician-selected mean arterial pressure target, in critically ill patients at least 65 years old. Methods For this multicenter observational study using data collected both prospectively and retrospectively, patients were recruited from five of the seven trial sites. We compared the mean arterial pressure of patients receiving vasopressors, who met or would have met trial eligibility criteria, from two periods: [1] at least 1 month before the trial started, and [2] during the trial period and randomized to usual care, or not enrolled in the trial. Results We included 200 patients treated before and 229 after trial initiation. There were no differences in age (mean 74.5 vs. 75.2 years; p = 0.28), baseline Acute Physiology and Chronic Health Evaluation II score (median 26 vs. 26; p = 0.47) or history of chronic hypertension (n = 126 [63.0%] vs. n = 153 [66.8%]; p = 0.41). Mean of the mean arterial pressure was similar between the two periods (72.5 vs. 72.4 mmHg; p = 0.76). Conclusions The initiation of a trial of a prescribed lower mean arterial pressure target, compared to a usual clinician-selected target, was not associated with a change in mean arterial pressure, reflecting stability in the net effect of usual clinician practices over time. Comparing prior and concurrent control groups may alleviate concerns regarding drift in usual practices over the course of a trial or permit quantification of any change.

Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms and are even more uncommon in the pediatric patients, thus leading to a lack of clinical research on diagnosis and management in this population. The purpose of this report is to review relevant literature and discuss a rare occurrence of a non-functioning pNET in a pediatric patient. This is a report of an 11-year-old male who presented with symptomatic anemia and was found to have a 6 cm mass near the pancreatic head with erosion into the duodenum. Surgical biopsy demonstrated a non-functioning pNET. He was successfully managed with complete surgical resection via a standard pancreaticoduodenectomy without evidence of recurrence after 1 year follow up. Further multi-institutional prospective studies or meta-analyses are warranted to further explore optimal management in the pediatric population.

Hepatic mesenchymal hamartomas (HMH) are benign liver lesions that present as cystic, slow growing masses within the first few years of life. Few cases demonstrate placental abnormalities and abnormal levels of alpha-fetoprotein (AFP). We report an unusual case of a rapidly growing HMH with associated placental anomalies and elevated AFP. A 2-month-old female born prematurely due to concerning placental findings presented with a prenatally-identified liver mass. Magnetic resonance imaging (MRI) showed a marked increase in the size of the mass over a three-month period. Prior to surgery, the AFP was elevated and decreased after operative resection. Histopathology confirmed the diagnosis HMH. Rapid growth of HMH is not commonly reported and raises concerns for malignancy. Abnormal placental findings may lead to prematurity, which can affect surgical management. We identified 27 cases of prenatally diagnosed HMH since 1983. The mean gestational age for identification was 29 weeks, with the majority managed by delayed resection. The timing for surgical intervention lacks consensus, but malnutrition and perioperative complications should be considered. High AFP levels with an infantile hepatic mass may indicate a more malignant process but does not exclude HMH.

Abstract This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.

Introduction Vasodilatory hypotension is common among intensive care unit (ICU) patients; vasopressors are considered standard of care. However, optimal mean arterial pressure (MAP) targets for vasopressor titration are unknown. The objective of the Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65) trial is to ascertain the effect of permissive hypotension (vasopressor titration to achieve MAP 60–65 mm Hg) versus usual care on biomarkers of organ injury in hypotensive patients aged ≥65 years.Methods and analysis OVATION-65 is an allocation-concealed randomised trial in 7 Canadian hospitals. Eligible patients are ≥65 years of age, in an ICU with vasodilatory hypotension, receiving vasopressors for ≤12 hours to maintain MAP ≥65 mm Hg during or after adequate fluid resuscitation, and expected to receive vasopressors for ≥6 additional hours. Patients are excluded for any of the following: active treatment for spinal cord or acute brain injury; vasopressors given solely for bleeding, ventricular failure or postcardiopulmonary bypass vasoplegia; withdrawal of life-sustaining treatments expected within 48 hours; death perceived as imminent; previous enrolment in OVATION-65; organ transplant within the last year; receiving extracorporeal life support or lack of physician equipoise. Patients are randomised to permissive hypotension versus usual care for up to 28 days. The primary outcome is high-sensitivity troponin T, a biomarker of cardiac injury, on day 3. Secondary outcomes include biomarkers of injury to other organs (brain, liver, intestine, skeletal muscle); lactate (a biomarker of global tissue dysoxia); resource utilisation; adverse events; mortality (90 days and 6 months) and cognitive function (6 months). Assessors of biomarkers, mortality and cognitive function are blinded to allocation.Ethics and dissemination This protocol has been approved at all sites. Consent is obtained from the eligible patient, the substitute decision-maker if the patient is incapable, or in a deferred fashion where permitted. End-of-grant dissemination plans include presentations, publications and social media platforms and discussion forums.Trial registration number NCT03431181.

Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration number NCT01782755; Pre-results.

The sole nonredundant role of the thymic medulla is to induce central tolerance, a vital process that depends on promiscuous gene expression (pGE), a unique feature of medullary thymic epithelial cells (mTECs). Although pGE enhances transcription of >3,000 genes in mTECs, its impact on the regulation of protein homeostasis remains unexplored. Here, we report that, because of pGE, mature mTECs synthesize substantially more proteins than other cell types and are exquisitely sensitive to loss of immunoproteasomes (IPs). Indeed, IP deficiency causes proteotoxic stress in mTECs and leads to exhaustion of postnatal mTEC progenitors. Moreover, IP-deficient mice show accelerated thymic involution, which is characterized by a selective loss of mTECs and multiorgan autoimmune manifestations. We conclude that pGE, the quintessential feature of mTECs, is a major burden for the maintenance of proteostasis, which is alleviated by the constitutive expression of IPs in mTECs.

An amendment to this paper has been published and can be accessed via the original article.

BACKGROUNDThe optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines.METHODIn a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively.RESULTSWe included data from 56 patients treated in 6 centers. The mean (standard deviation [SD]) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (pCONCLUSIONSIn this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site.

Esophageal dilation is a rare complication of scleroderma and CREST syndrome. A case of atelectasis secondary to right inferior bronchus compression by a massively dilated esophagus is described. The authors are unaware of any previous cases of atelectasis secondary to esophageal dilation in scleroderma.

Abstract Ballots are the core records of elections. Electronic records of actual ballots cast (cast vote records) are available to the public in some jurisdictions. However, they have been released in a variety of formats and have not been independently evaluated. Here we introduce a database of cast vote records from the 2020 U.S. general election. We downloaded publicly available unstandardized cast vote records, standardized them into a multi-state database, and extensively compared their totals to certified election results. Our release includes vote records for President, Governor, U.S. Senate and House, and state upper and lower chambers, covering 42.7 million voters in 20 states who voted for more than 2,200 candidates. This database serves as a uniquely granular administrative dataset for studying voting behavior and election administration. Using this data, we show that in battleground states, 1.9 percent of solid Republicans (as defined by their congressional and state legislative voting) in our database split their ticket for Joe Biden, while 1.2 percent of solid Democrats split their ticket for Donald Trump.

Abstract Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: “Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature”. Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of “a globally coordinated diagnostic and research pipeline”. To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient’s diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease.

In vitro assessments for the prediction of pharmacokinetic (PK) behavior of biotherapeutics can help identify corresponding liabilities significantly earlier in the discovery timeline. This can minimize the need for extensive early in vivo PK characterization, thereby reducing animal usage and optimizing resources. In this study, we recommend bolstering classical developability workflows with in vitro measures correlated with PK. In agreement with current literature, in vitro measures assessing nonspecific interactions, self-interaction, and FcRn interaction are demonstrated to have the highest correlations to clearance in hFcRn Tg32 mice. Crucially, the dataset used in this study has broad sequence diversity and a range of physicochemical properties, adding robustness to our recommendations. Finally, we demonstrate a computational approach that combines multiple in vitro measurements with a multivariate regression model to improve the correlation to PK compared to any individual assessment. Our work demonstrates that a judicious choice of high throughput in vitro measurements and computational predictions enables the prioritization of candidate molecules with desired PK properties.

BackgroundSexual minority men are disproportionately affected by methamphetamine use, with recent studies suggesting an increase in use specifically among Black sexual minority men. Black sexual minority men face unique structural barriers to achieving optimal health. Given its harmful effects, and in light of existing health disparities, an increase in methamphetamine use among Black sexual minority men poses a significant public health concern. ObjectiveThe Health Impacts and Struggles to Overcome the Racial Discrimination of Yesterday (HISTORY) study is investigating the potential impacts of exposure to the census tract–level structural racism and discrimination (SRD) on methamphetamine use among Black sexual minority men in Atlanta, Georgia, and will identify intervention targets to improve prevention and treatment of methamphetamine use in this population. MethodsThis study uses a mixed methods and multilevel design over a 5-year period and incorporates participatory approaches. Individual-level quantitative data will be collected from a community-based cohort of Black sexual minority men (N=300) via periodic assessment surveys, ecological momentary assessments, and medical record abstractions. Census tract–level measures of SRD will be constructed using publicly available administrative data. Qualitative data collection will include longitudinal, repeated in-depth interviews with a subset (n=40) of study participants. Finally, using a participatory group model–building process, we will build on our qualitative and quantitative data to generate causal maps of SRD and methamphetamine use among Black sexual minority men, which in turn will be translated into actionable recommendations for structural intervention. ResultsEnrollment in the HISTORY study commenced in March 2023 and is anticipated to be completed by November 2024. ConclusionsThe HISTORY study will serve as a crucial background upon which future structural interventions can be built, to mitigate the effects of methamphetamine use and SRD among Black sexual minority men. International Registered Report Identifier (IRRID)DERR1-10.2196/63761

Abstract The capability to anticipate the exceptionally rapid warming of the Northwest Atlantic Shelf and its evolution over the next decade could enable effective mitigation for coastal communities and marine resources. However, global climate models have struggled to accurately predict this warming due to limited resolution; and past regional downscaling efforts focused on multi‐decadal projections, neglecting predictive skill associated with internal variability. We address these gaps with a high resolution (1/12°) ensemble of dynamically downscaled decadal predictions. The downscaled simulations accurately predicted past oceanic variability at scales relevant to marine resource management, with skill typically exceeding global coarse‐resolution predictions. Over the long term, warming of the Shelf is projected to continue; however, we forecast a temporary warming pause in the next decade. This predicted pause is attributed to internal variability associated with a transient, moderate strengthening of the Atlantic meridional overturning circulation and a southward shift of the Gulf Stream.

Abstract Global Earth system models are often enlisted to assess the impacts of climate variability and change on marine ecosystems. In this study, we compare high frequency (daily) outputs of potential ecosystem stressors, such as sea surface temperature and surface pH, and associated variables from an Earth system model (GFDL ESM4.1) with high frequency time series from a global network of moorings to directly assess the capacity of the model to resolve local biogeochemical variability on time scales from daily to interannual. Our analysis indicates variability in surface temperature is most consistent between ESM4.1 and observations, with a Pearson correlation coefficient of 0.93 and bias of 0.40°C, followed by variability in surface salinity. Physical variability is reproduced with greater accuracy than biogeochemical variability, and variability on seasonal and longer time scales is more consistent between the model and observations than higher frequency variability. At the same time, the well‐resolved seasonal and longer timescale variability is a reasonably good predictor, in many cases, of the likelihood of extreme events. Despite limited model representation of high frequency variability, model and observation‐based assessments of the fraction of days experiencing surface T‐pH and T‐Ωarag multistressor conditions show reasonable agreement, depending on the stressor combination and threshold definition. We also identify circumstances in which some errors could be reduced by accounting for model biases.

Fusarium wilt of banana (FWB), caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc), poses an undeniable threat to global banana production. This disease has intensified in recent years, with the tropical race 4 (TR4) strain spreading rapidly. Since 2018, the number of affected countries has increased from 16 to 23, presenting a significant challenge to researchers, producers, and National Plant Protection Organizations (NPPOs) worldwide. The potential impact of TR4 in Latin America and the Caribbean (LAC) is particularly concerning. This region boasts seven of the top ten banana-exporting countries, and bananas and plantains are crucial for food security and income generation. In Colombia, where TR4 was detected in 2019, the disease has already spread from La Guajira to Magdalena, and it is currently affecting 20 large commercial export farms. In Peru, the disease was detected in 2021 and although still restricted to the northern region, flood irrigation and heavy rains associated with the Yaku cyclone, boosted pathogen spread, and more than 400 small organic banana farmers are currently affected. In Venezuela, TR4 detection occurred in 2023, with plantations across three states and five municipalities now affected. Worryingly, TR4 has also been confirmed in plantains, a staple food in the region. Current national responses in LAC primarily rely on preventive and reactive measures: preventing initial incursions and containing outbreaks to avoid further spread. However, the disease’s relentless progression suggests that its eventual presence in all banana-producing areas is likely. Therefore, exploring alternative management approaches beyond pathogen exclusion becomes crucial, both in affected and disease-free regions. This paper examines the current spread of TR4, focusing on epidemiological aspects and recent research-based management options. Key epidemiological features were highlighted, drawing practical examples from various scales (plots to landscapes) and utilizing experiences from LAC’s fight against TR4. The paper also reviews field-tested approaches in biosecurity, biological control, resistant varieties, soil health, and integrated disease management, acknowledging the specific challenges faced by smallholder settings. In each section research initiatives were analyzed, identifying gaps, and proposing directions to minimize TR4 impact and accelerate the development of sustainable solutions for managing this devastating disease.

Abstract Background An inability to successfully recruit participants into clinical research has consequences that negatively affect the conduct and reliability of research studies. Understanding facilitators of research participation, namely motives for participation and preferred research outcomes, may improve recruitment and retention of clinical trials related to chronic pain. The present study explored research participation facilitators among individuals with chronic pain and their association with demographic characteristics, pain-related characteristics, and factors related to future research engagement. Methods Individuals from Michigan who were 18 years or older and self-reported having chronic pain completed an online survey assessing motives for research participation and desired research outcomes. Analyses were conducted in three stages. First, we evaluated underlying factors of motives for participation and research outcome preferences using principal components analysis. Second, we classified individuals according to their patterns of facilitators using latent profile analysis. Finally, we evaluated differences between facilitator profiles in demographic characteristics, pain-related characteristics, and factors related to future research engagement using χ2 analyses and Kruskal-Wallis rank sum tests. Results Three components of motives for research participation were identified: social engagement/enjoyment; pain improvement/advancing science; and compensation. Three components of research outcome preferences were identified: co-occurring symptom reduction; behavior reduction modification; and pain and function improvement. Four potential patient-centered profiles utilizing these dimensions of facilitators were identified that had unique demographic characteristics, research participation willingness, and treatment interest. Conclusions Our data provide a framework of motives and research outcome preferences that may inform recruitment and retention in chronic pain research. It also gives an indication of who may respond best to active or passive recruitment strategies that appeal to a given motive or preferred outcome. This information may be useful for improving recruitment and to monitor any potential biases in participant samples.

Spinal cord hemangiomas are rare vascular malformations that can cause neurological deficits. We report a case of a 57-year-old male who previously underwent spondylolisthesis reduction for treatment of a 30% (1 cm) anterolisthesis of L4-L5 with continued neurological deficit post-operatively. The patient still reported bilateral lower extremity weakness, and he was found to have an additional ovoid intramedullary lesion at the T2-T3 level, pathologically consistent with a hemangioma. The patient underwent a T2-T3 laminectomy, and the lesion was resected without any complications. Histopathological examination confirmed the diagnosis of hemangioma. Postoperatively, the patient showed significant improvement in his lower extremity weakness and back pain. Hemangiomas are rare lesions that account for less than 5% of all spinal cord tumors. They consist of vessels similar to those of embryonic capillaries and can cause pressure on the surrounding neural tissue, leading to neurological deficits. MRI is the imaging modality of choice for diagnosing spinal cord hemangiomas. Hemangiomas typically demonstrate mixed signal intensities on T1-weighted images, depending on the fat content of the lesion. They usually demonstrate high T2 signal intensity due to high water content, and avid contrast enhancement due to high vascularity. Surgical resection is the treatment of choice for symptomatic hemangiomas, and complete resection is associated with a good prognosis.

Aims Eating disorders often present as a significant challenge in adolescents; especially with regards to early diagnosis and intervention. This case report explores the complex presentation of a 15-year-old female initially suspected of having an eating disorder. The complexity in this case lies in the differentiation between a formal eating disorder and disordered eating, emphasising the importance of thorough assessment and understanding of the underlying psychological factors. Methods This patient presented to the CAMHS eating disorders team having lost 14 kg in 6 weeks. Such an alarming weight loss had triggered the urgent referral and review. These symptoms initially suggested a classic eating disorder. However as the patient spent more time on the physical health ward a comprehensive evaluation revealed underlying issues related to body image, self-esteem, and emotional wellbeing as well as complex family dynamics leading to a diagnosis of disordered eating rather than a specific eating disorder. The multidimensional approach involved collaboration between mental health professionals, paediatricians and dieticians, to address the multifaceted nature of the condition whilst the patient was admitted to a physical health ward. Results The case highlights the intricate interplay between physical and psychological factors contributing to disordered eating behaviours in adolescence. Factors such as societal pressures, peer influences, personal expectations as well as dynamics within a family home may all contribute to a distorted relationship with food and body image. Recognising these complexities is crucial for tailored interventions that address the root causes rather than merely focusing on symptomatic relief. We also established in this case the difference in efficacy between utilising aripiprazole vs olanzapine in terms of treatment of anorexic cognitions. Conclusion This case study underscores the necessity of a thorough and holistic approach in assessment, diagnosis and management of eating-related concerns in adolescents. By differentiating between eating disorders and disordered eating, healthcare professionals may better accommodate interventions to address the specific needs of the individual. Early identification and comprehensive care, involving medical, nutritional, and psychological components, are essential for promoting healthy relationships with food and preventing the escalation of disordered eating into more severe conditions.

Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors’ needs.

Although most patients with cardiac amyloidosis are diagnosed with either light chain (AL) or transthyretin (ATTR) disease, coexisting amyloid subtypes can occur. We present three cases of coexisting AL and ATTR cardiac amyloidosis and demonstrate the importance of clinical history and endomyocardial biopsy in diagnosis of this rare entity.

Abstract The aim of this study was to investigate the ability of shell (coating) formulations comprised of alginate and glucono delta lactone (GDL) to encapsulate a mixture of green tea and turmeric extracts. Three concentrations of alginate and GDL were used at 0.5%, 0.75%, and 1%, w/v and their solid ratio was varied using a factorial design. A response surface model was applied to optimize the retention of catechin and curcuminoid contents, to determine encapsulation efficiency, and to minimize undesirable flavor and taste. Increasing the concentration of alginate and GDL significantly increased the retention of catechin and curcuminoid contents, encapsulation efficiency, and consumer acceptance (p

Abstract We consider a heterotic version of six-dimensional Kodaira-Spencer gravity derived from the heterotic superpotential. We compute the one-loop partition function and find it can be expressed as a product of holomorphic Ray-Singer torsions. We discuss its topological properties and potential gauge and gravitational anomalies. We show these anomalies can be cancelled using Green-Schwarz-like counter-terms. We also discuss the dependence on the background geometry, and in particular the choice of hermitian metric needed for quantisation. Given suitable topological constraints, this dependence may again be cancelled by the addition of purely background-dependent counter-terms. We also explain how our methods provide the one-loop partition functions of a large class of more general holomorphic field theories in terms of holomorphic Ray-Singer torsions.

Wasted produce is a pertinent issue in agriculture, with billions of tons of produce going to waste even before it hits markets. Specifically, in Sub-Saharan Africa (SSA), nearly half of all produce is lost before market. To combat this, the Agricycle® passive solar drier was designed to provide a cost-effective method of drying fruit for preservation. Using a psychrometric chamber to simulate the SSA environment, vitamin C, total phenolic contents, and iron tests were conducted, along with microbial content determination, water content determination, dissolved solids testing, and color and microstructure analyses to validate passive solar drying, comparing the results to freeze-dried samples. Nutritional contents were comparable between fresh, freeze-dried, and solar-dried samples, with a loss in vitamin C (statistically significant), total phenolic contents, and dissolved solids during solar drying. The microbial analysis for solar-dried samples was below standard limits, and the water content in the solar-dried samples was ~10% w.b. (® passive solar drier is a promising alternative approach for food preservation.

Lima La Vieja es un sitio arqueológico a punto de desaparecer. A pesar de que ha sido objeto de estudios arqueológicos e históricos a lo largo del siglo XX y de que su arquitectura y función lo destacan entre otros asentamientos incas, el sitio ha sido gradualmente desmantelado a lo largo de los siglos XX y XXI. Lima La Vieja es muy importante dentro del sistema mayor del estado Inca en esta región y es además uno de los primeros asentamientos españoles fundados en el siglo XVI en Pisco y el Sur de Perú. Nuestro artículo reconstruye el asentamiento de Lima La Vieja mediante información inédita y el uso de nuevas metodologías, con el objetivo de contextualizar este sitio dentro del registro histórico y arqueológico del valle de Pisco, especialmente durante el Horizonte Tardío.

Background: Although there is much literature demonstrating weight changes in professional mixed martial arts (MMA) athletes, there is minimal data comparing male and female MMA athletes. Therefore, the purpose of the current study was to compare weight changes between professional male and female MMA athletes leading up to competition. Methods: One hundred and three professional flyweight MMA athletes competing for the Ultimate Fighting Championship (UFC) were used for the study. Weight was obtained at multiple time points leading up to the competition. Two-way ANOVAs and post hoc t-tests were used, and significance was set at p ≤ 0.05. Results: ANOVA revealed there was a significant main effect of condition for weight changes (p < 0.001) and a significant main effect of sex on weight changes (p = 0.002) prior to competition. Post hoc analysis revealed that males lost more weight prior to the official weigh-in and gained more weight prior to competition when compared to females (p ≤ 0.05). Conclusion: MMA athletes lose weight prior to the official weigh-in and gain weight prior to competition. Moreover, male MMA athletes lose more weight prior to and gain more weight after when compared to female MMA athletes competing in the UFC’s flyweight division.

En este artículo se describen nuestras investigaciones arqueológicas en Pozuelo, el sitio arqueológico con la cerámica más temprana del valle de Chincha, ubicado en la costa sur del Perú. Nuestras investigaciones confirman las relaciones estilísticas de la cerámica más temprana de Pozuelo con sus contemporáneas de otros sitios de la costa sur, central y norte durante los siglos VIII y V a.C. Coincidentemente, este también es el periodo de máxima ocurrencia de la cerámica conocida en la literatura arqueológica como “Chavinoide” o “Janabarroide”. Por tanto, Pozuelo representa la manifestación más temprana de la sedentarización, producción de espacios sociales y laborales en el valle de Chincha, un desarrollo social endógeno, pero también asociado al fenómeno Chavín de carácter más extendido en el área andina.

During the last 2–3 decades there has been increasing attention from academics, professionals and consumers about how phenolic compounds from plant based foods could enhance the nutritional quality of foods. This mini-review evaluates the focus given to the interactions phenolics have on the metabolic functions in foods and how these phenolic compounds can manipulate digestibility of both carbohydrates and proteins, and how this in turn can modulate metabolic disorders as well as microbiota. With an emphasis on research published in the last decade, the article also examines the potential of valorisation strategies to reutilise fractions which may have traditionally been lost in the food production operations. The reason for this focus is related to the pressing requirements of sustainability within the resource hungry food industry, and how we can create a culture of regenerative food innovation within the sectors.

Background It is common practice for fight sport athletes to use a variety of weight manipulation strategies to compete in desired weight classes. Although numerous studies have highlighted rapid weight loss (RWL) strategies and the magnitude of weight loss, few have focused specifically on weight loss in female fighters. The purpose of this study was to provide descriptive information on professional UFC female fighters engaging in RWL in all women’s UFC weight divisions: strawweight (52.2 kg): flyweight (56.7 kg); bantamweight (61.2 kg); featherweight (65.8 kg). Methods All fighter’s weights were obtained at five separate time points: 72 hrs. pre-weigh-in, 48 hrs. pre-weigh-in, 24hrs. pre-weigh-in, official weigh-in, and 24 hrs. post-weigh-in (competition weight). Mixed effects models and random effects analysis were used to assess changes in weight and differences between weight divisions. All statistics were analyzed, and significance was set at p ≤0.05. Significant changes in weight between all time points were reported. Results No statistical differences between weight divisions were observed. Female fighters lost 4.5–6.6% of their weight prior to the official weigh-in. Conclusion Females engaged in RWL practices lose weight in a similar fashion irrespective of weight class.

Abstract Background The use of insecticide-treated bed nets has been proven to be effective in reducing malaria transmission in highly endemic areas. Use of long-lasting insecticidal nets (LLINs) has been embraced by many malaria endemic countries. LLINs are up to 95% effective in inhibiting blood feeding, when used consistently even after 7 years. The challenge, however, is enhancing their consistent use, especially by the most vulnerable groups (children under 5 years and pregnant women). The study established factors associated with consistent use of bed nets for malaria control among children under 5 years in Soroti district. Methods The study employed a cross-sectional design, with multi-stage sampling of households. A total of 400 households (HH) were sampled and the HH head in each household interviewed. Key informant interviews (KIIs) were conducted with 7 key informants who were knowledgeable on the subject matter. Data analysis was done using SPSS 17.0 at Univariate, Bivariate and Multivariable levels; after entry and cleaning. Key informants’ data were summarized manually; verbatim quotes and text used to reinforce quantitative data in line with objectives. Results Only 56.8% of the 690 children under 5 years used bed nets consistently. The factors affecting consistent bed net use were age of the child, their use of bed nets the previous night, occupation of caretaker, respondents’ perceived susceptibility, perceived risk of getting malaria, size and shape of the bed nets. Rectangular nets were difficult to hang daily in huts according to most key informants. Conclusion Consistent bed net use among under fives is still below the RBM target of 85% by 2015 and can be enhanced by providing conical bed nets and setting aside a health education programme to emphasize the effectiveness of even one mosquito in spreading malaria at night to the entire household and ability of bed nets to stop transmission better than other methods.

Measurement(s) Election results Technology Type(s) Scripts for collection, cleaning, and quality assurance

Objective Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID).Methods and analysis We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began.Results The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence.Conclusions We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence.Trial registration number NCT00116090.

IntroductionVariation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers.MethodsPBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created.Results67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)].ConclusionDifferences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans.

Background The identification of large‐artery stiffness as a major, independent risk factor for cardiovascular disease–associated morbidity and death has focused attention on identifying therapeutic strategies to combat this disorder. Genetic manipulations that delete or inactivate the translin/trax microRNA‐degrading enzyme confer protection against aortic stiffness induced by chronic ingestion of high‐salt water (4%NaCl in drinking water for 3 weeks) or associated with aging. Therefore, there is heightened interest in identifying interventions capable of inhibiting translin/trax RNase activity, as these may have therapeutic efficacy in large‐artery stiffness. Methods and Results Activation of neuronal adenosine A2A receptors (A2ARs) triggers dissociation of trax from its C‐terminus. As A2ARs are expressed by vascular smooth muscle cells (VSMCs), we investigated whether stimulation of A2AR on vascular smooth muscle cells promotes the association of translin with trax and, thereby increases translin/trax complex activity. We found that treatment of A7r5 cells with the A2AR agonist CGS21680 leads to increased association of trax with translin. Furthermore, this treatment decreases levels of pre‐microRNA‐181b, a target of translin/trax, and those of its downstream product, mature microRNA‐181b. To check whether A2AR activation might contribute to high‐salt water–induced aortic stiffening, we assessed the impact of daily treatment with the selective A2AR antagonist SCH58261 in this paradigm. We found that this treatment blocked aortic stiffening induced by high‐salt water. Further, we confirmed that the age‐associated decline in aortic pre‐microRNA‐181b/microRNA‐181b levels observed in mice also occurs in humans. Conclusions These findings suggest that further studies are warranted to evaluate whether blockade of A2ARs may have therapeutic potential in treating large‐artery stiffness.

Este artículo presenta los resultados de una investigación sobre las experiencias de un grupo de docentes que laboran en el estado de Chiapas, México. El objetivo es documentar y analizar algunos elementos nucleares de su aprendizaje sobre el funcionamiento del sistema educativo en el cual están inmersos, un aprendizaje que se asemeja a lo que se entiende por la noción de un currículo oculto. Desde un paradigma constructivista y un enfoque biográfico, se realizaron entrevistas abiertas a nueve docentes de primaria que laboran en Chiapas. Mediante un análisis interpretativo, se identificó el aprendizaje de la desconfianza como una característica emergente y constante en sus relatos. Los resultados fueron categorizados en tres campos relacionales en los que aprender a desconfiar parece ser determinante en cuanto a su práctica e identidad: el gobierno y las autoridades; compañeras y compañeros docentes; y madres y padres de familia. También, se observa la necesidad del trabajo colaborativo y sinérgico, con posturas aprendidas que cierran esta posibilidad y perpetúan los mismos sentimientos de desconfianza y un ambiente adverso. Estas posturas tienen una clara implicación en el aprendizaje de los estudiantes, al alterar el buen funcionamiento de las escuelas, así como el clima escolar.

We present a set of generalized quantum loop models that provably exhibit topologically stable ergodicity breaking. These results hold for both periodic and open boundary conditions, and derive from a one-form symmetry (notably not being restricted to sectors of extremal one-form charge). We identify simple models in which this one-form symmetry can be emergent, giving rise to the aforementioned ergodicity breaking as an exponentially long-lived prethermal phenomenon. We unveil a web of dualities that connects these models, in certain limits, to models that have previously been discussed in the literature. We also identify nonlocal conserved quantities in such models, which correspond to patterns of system-spanning domain walls and are robust to the addition of arbitrary $k$-local perturbations.

Food losses in the agri-food sector have been estimated as representing between 30 and 80% of overall yield. The agro-food sector has a responsibility to work towards achieving FAO sustainable goals and global initiatives on responding to many issues, including climate pressures from changes we are experiencing globally. Regenerative agriculture has been discussed for many years in terms of improving our land and water. What we now need is a focus on the ability to transform innovation within the food production and process systems to address the needs of society in the fundamental arenas of food, health and wellbeing in a sustainable world. Thus, regenerative food innovation presents an opportunity to evaluate by-products from the agriculture and food industries to utilise these waste streams to minimise the global effects of food waste. The mini-review article aims to illustrate advancements in the valorisation of foods from some of the most recent publications published by peer-reviewed journals during the last 4–5 years. The focus will be applied to plant-based valorised food products and how these can be utilised to improve food nutritional components, texture, sensory and consumer perception to develop the foods for the future.