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Obesity is one of the leading preventable causes of cancer; however, little is known about the effects of obesity on anti-tumor immunity. Here, we investigated the effects of obesity on CD8 T cells in mouse models and patients with endometrial cancer. Our findings revealed that CD8 T cell infiltration is suppressed in obesity, which was associated with a decrease in chemokine production. Tumor-resident CD8 T cells were also functionally suppressed in obese mice, which was associated with a suppression of amino acid metabolism. Similarly, we found that a high BMI negatively correlated with CD8 infiltration in human endometrial cancer and that weight loss was associated with a complete pathological response in six of nine patients. Moreover, immunotherapy using anti–PD-1 led to tumor rejection in lean and obese mice and partially restored CD8 metabolism and anti-tumor immunity. These findings highlight the suppressive effects of obesity on CD8 T cell anti-tumor immunity, which can partially be reversed by weight loss and/or immunotherapy.

An exact formula is derived, as an integral, for the mean square value of the winding angle ϕ (with −∞< ϕ t, around an infinitely long impenetrable cylinder of radius a, having started at radius R(>a) from the axis. Strikingly, for the simpler problem with a = 0, the mean square winding angle around a straight line, is long known to be instantly infinite however far away the starting point lies. The fractally small, fast, random walk steps of mathematical Brownian motion allow unbounded windings around the zero thickness of the straight line. A remedy, if it is required, is to accord the line non-zero thickness, an impenetrable cylinder, as analysed here. The problem straightaway reduces to a 2D one of winding around a disc in a plane since the axial component of the 3D Brownian motion is independent of the others. After deriving the exact mean square winding angle, the integral is evaluated in the limit of a narrow cylinder a 2 ≪ R 2, highlighting the limits of short and long diffusion times addressed by previous approximate treatments.

SALT, a new dedicated readout Application Specific Integrated Circuit (ASIC) for the Upstream Tracker, a new silicon detector in the Large Hadron Collider beauty (LHCb) experiment, has been designed and developed. It is a 128-channel chip using an innovative architecture comprising a low-power analogue front-end with fast pulse shaping and a 40 MSps 6-bit Analog-to-Digital Converter (ADC) in each channel, followed by a Digital Signal Processing (DSP) block performing pedestal and Mean Common Mode (MCM) subtraction and zero suppression. The prototypes of SALT were fabricated and tested, confirming the full chip functionality and fulfilling the specifications. A signal-to-noise ratio of about 20 is achieved for a silicon sensor with a 12 pF input capacitance. In this paper, the SALT architecture and measurements of the chip performance are presented.

Grazing plays an important role in milk production in most regions of the world. In this review, some challenges to the grazing cow are discussed together with opportunities for future improvement. We focus on daily feed intake, efficiency of pasture utilization, output of milk per head, environmental impact of grazing and the nutritional quality to humans of milk produced from dairy cows in contrasting production systems. Challenges are discussed in the context of a trend towards increased size of individual herds and include limited and variable levels of daily herbage consumption, lower levels of milk output per cow, excessive excretion of nitrogenous compounds and requirements for minimal periods of grazing regardless of production system. A major challenge is to engage more farmers in making appropriate adjustments to their grazing management. In relation to product quality, the main challenge is to demonstrate enhanced nutritional/processing benefits of milk from grazed cows. Opportunities include more accurate diet formulations, supplementation of grazed pasture to match macro‐ and micronutrient supply with animal requirement and plant breeding. The application of robotics and artificial intelligence to pasture management will assist in matching daily supply to animal requirement. Wider consumer recognition of the perceived enhanced nutritional value of milk from grazed cows, together with greater appreciation of the animal health, welfare and behavioural benefits of grazing should contribute to the future sustainability of demand for milk from dairy cows on pasture.

Background Obesity drives endometrial cancer (EC). Metabolic surgery (MS) induces sustained weight loss, reduces EC risk and has been shown to reverse histological changes of endometrial hyperplasia. One mechanism is increased GLP-1 post surgery. Few interventional studies have been conducted in the BDII/Han rat; an animal model of spontaneous EC. This study aimed to examine whether high fat diet (HFD) and weight gain, as well as subsequent intentional weight loss using Liraglutide (a GLP-1 receptor agonist) alters EC tumour biology and burden in the BDII/Han rat. A rat imaging protocol was validated to assess development and longitudinally track tumours. Methods An imaging protocol was developed and validated. 7 BDII/Han rats were fed normal chow (NC) and 8 weight-matched rats fed HFD from 3 months of age. Longitudinal PET-CT was conducted at 7, 9, 12 and 15 months. Abdominal visceral fat was analysed from L1-L5 on CT. Subsequently, an intervention study compared the 8 HFD-Control rats to 8 weight-matched HFD-fed rats treated with Liraglutide from 12-15 months. PET-CT was used to assess disease progression. Analysis of histological, immunohistochemical and transcriptomic parameters were used to compare cohorts. All rats were euthanased aged 15-months. Imaging was correlated with necropsy findings and histopathology. Results HFD rats had more abdominal fat on CT imaging (8.6cm3±0.7vs4.0cm3±0.6;p Conclusions This study has established a safe, sensitive and specific imaging protocol for longitudinal assessment of EC progression in BDII/Han rats. The HFD intervention used did not accelerate EC burden. However, it did create an obese phenotype and gave new information on the pathological variations of EC in the BDII/Han rat. Intentional weight loss from Liraglutide halved EC burden compared to controls in this study. An absence of GLP-1R expression may suggest weight loss dependent mechanisms. This novel pilot study is a foundation for future studies assessing the effect of intentional weight loss using metabolic surgery in obesity-related cancer.

The only evidence that seeing in slow-motion exists comes from retrospective interviews. An ongoing debate is whether this phenomenon exists as a figment of memory or a true function of visual perception. Testing these speculations is difficult given slow-motion experience is often associated with intense, stressful, and even threatening situations that dramatically heighten arousal. Virtual reality systems might provide an opportunity to study the experience online, thus offering insights into the speculated mechanisms. This study explores the feasibility to induce heightened arousal and its possible implications on perceptual encoding of information. Participants were exposed to various situations designed to influence arousal as measured by heart rate, and an implicit memory task was used for each situation to test perceptual processing. This study did not reveal performance gains associated with increased physiological arousal.

We gathered data from three pipeline databases and other public sources on development stage and clinical trial metrics for 1,914 investigational drugs, biologics, and vaccines and 2,769 clinical trials intended to treat a wide variety of infectious diseases. We included new molecular entities (NMEs), new formulations, and new combinations. Clinical trial times decreased from 2000-2008 to 2009-2017, varied by disease class, and were longer for trials with more subjects or more sites. Clinical approval success rates were higher for this set of diseases than those in the published literature for drugs across all therapeutic categories. NMEs to treat HIV had a success rate (16.0%) that was similar to those for drugs in general, whereas NME success rates for influenza and pneumonia were much higher (48.1% and 50.5%, respectively).

Purpose The Tufts Center for the Study of Drug Development (CSDD) and the Drug Information Association (DIA) in collaboration with 8 pharmaceutical and biotechnology companies conducted a study examining the adoption and effect of artificial intelligence (AI), such as machine learning, on drug development. The study was conducted to clarify and understand AI adoption across the industry and to gather detailed insights into the spectrum of activities included in the definition of AI. The study investigated and identified analytical platforms and innovations across pharmaceutical and biotechnology companies currently being used or planned for in the future. Methods A 2-part method was used that comprised in-depth interviews with AI industry experts and a global survey conducted across pharmaceutical and biotechnology organizations. Eleven in-depth interviews focused on use and implementation of AI across drug development. The survey assessed use of AI and included perceptions about current and future use. The survey also examined technology definitions, assessment of organizational and personal AI expertise, and use of partnerships. A total of 402 responses, including data from 217 unique organizations, were analyzed. Findings Although 7 in 10 respondents reported using AI in some capacity, a wide range of use was reported by AI type. Patient selection and recruitment for clinical studies was the most commonly reported AI activity, with 34 respondents currently using AI for this activity. In addition, identification of medicinal products data gathering was the top activity being piloted or in the planning stages, reported by 49 respondents. The study also revealed that the most significant challenges to AI implementation included staff skills (55%), data structure (52%), and budgets (49%). Nearly 60% of respondents noted planned increases in staff within 1–2 years to support AI use or implementation. Implications Despite the challenges to AI implementation, the survey revealed that most organizations use AI in some capacity and that it is important to the success of an organization's workforce. Many organizations reported expectations for increasing staff as implementation of AI expands. Further research should examine the changing development landscape as the role of AI evolves.

BACKGROUND Predicting survival of patients with spinal metastases would help stratify treatments from aggressive to palliation. OBJECTIVE To evaluate whether sarcopenia predicts survival in patients with lung, breast, prostate, or multiple myeloma spinal metastases. METHODS Psoas muscle measurements in patients with spinal metastasis were taken from computed tomography scans at 2 time points: at first episode of stereotactic body radiation therapy (SBRT) and from the most recent scan available. Overall survival and hazard ratios were calculated with multivariate cox proportional hazards regression analyses. RESULTS In 417 patients with spinal metastases, 40% had lung cancer, 27% breast, 21% prostate, and 11% myeloma. Overall survival was not associated with age, sex, ethnicity, levels treated, or SBRT volume. Multivariate analysis showed patients in the lowest psoas tertile had shorter survival (222 d, 95% CI = 185-323 d) as compared to the largest tertile (579 d, 95% CI = 405-815 d), (HR1.54, P = .005). Median psoas size as a cutoff value was also strongly predictive for survival (HR1.48, P = .002). Survival was independent of tumor histology. The psoas/vertebral body ratio was also successful in predicting overall survival independent of tumor histology and gender (HR1.52, P

BACKGROUND: Ultrasound is increasingly used in labour; however, little data exist on attitudes to its use. We sought to analyse and compare the views of pregnant women, midwives, and a women's panel on the value and use of ultrasound in labour. METHODS: Focus groups involving a short presentation on ultrasound, questionnaire, and a question and answer session were held with groups of pregnant women, midwives at 2 inner‐city maternity units, and a RCOG online Women's Panel. Data were collected on attitudes to vaginal examination, ultrasound, predicting Caesarean section, and the utility of a digital representation of labour. RESULTS: Twenty one midwives and 29 service users (19 pregnant women and 10 women's panel members) participated. Significantly more service users saw positive value in intrapartum ultrasound (P = 0.0005) and predicting Caesarean section (P = 0.03) than midwives. The majority of both groups – 72% (20/29) and 62% (13/21), respectively – thought women would want a digital representation of their labour, with the most popular format being on a mobile phone (56%, 20/36). CONCLUSIONS: Service users were most and midwives least positive about ultrasound versus vaginal examination, indicating divergence between midwives' perspective of women's need to understand risk and desire to know about their labour. Women found the non‐intrusive nature and accuracy of ultrasound valuable while midwives were concerned about de‐skilling and medicalisation of birth. All groups felt a graphical representation of labour on a device would be helpful.

Sex differences are evident in the incidence, therapeutic response and survival of patients with various cancers including the most common, aggressive and incurable GBM. We generated a murine GBM model of male and female astrocytes with dual loss of NF1 and P53 that yielded a sex-biased transformation of the astrocytes with male cells being significantly more tumorigenic and therapeutically resistant compared to female cells. In our current work, we aimed to delineate the molecular mechanisms driving this sex-biased tumorigenic phenotype in order to deliver therapies that are more effective to patients with GBM. We examined the inhibition of KLF5 on tumorigenic phenotypes using cellular bio-functional assays. We used barcoded transposon calling cards to determine the genomic localization of KLF5 and the differentially induced gene expression in male versus female GBM cells. Chemical inhibition or shRNA knock-down of KLF5 significantly reduced proliferation, migration, clonogenic stem-cell frequency and survival, but increase apoptosis in male and female GBM cells. Interestingly, male, but not female, GBM cells exhibited an increased migratory phenotype after radiation that inhibition of KLF5 significantly reduced. Moreover, KLF5 inhibition significantly reduced the protein expression of tumorigenic PDGFRB, AKT, ERK and the stem marker Sox-2. Transposon calling cards mapped unique KLF5 genomic localization in male versus female GBM cells with significantly differential gene expression profiles between the two. The top genes induced by KLF5 in male cells were primarily affiliated with poorer prognosis and reduced survival, whereas in female cells they were affiliated with better prognosis and improved survival in patients with cancer. Our findings provide a promising exploratory avenue for KLF5 as a therapeutic target in GBM and warrants further investigation in order to delineate the precise molecular mechanisms driving this antitumor response so that targeted therapy would be more effective taking into consideration the sex-differences in patients with GBM.

The contents of the human orbit develop from all embryonic germinal layers to form diverse and specialized interconnected structures, whose unified function is that of providing sight. A thorough knowledge of these structures and their inter-relationships is imperative for the head and neck surgeon. This article will discuss the structures contained within the orbit from a surgical perspective in the hope of expanding the head and neck surgeon's knowledge and comfort when treatment indication necessitates entry into this space.

Fractures of the orbit are a very common injury, and are often treated by multiple facial subspecialties. Many fractures can be asymptomatic and do not require surgical therapy, but for those fractures where intervention is indicated, neglect, delay, or inappropriate technique can have permanent consequences on visual function and facial deformity. In this article, the indications and techniques of repair for specific fractures will be discussed, as well as possible risks and complications.

Substitution of fossil fuels by sustainable practices must be rapidly implemented to mitigate the impacts of climate change. The conversion of biomass into combustible gas is investigated in a microwave-induced plasma reactor using pure steam as the plasma working gas for the first time. The optimum results are achieved at the highest forward microwave power of 6 kW with biomass carbon conversion efficiency over 98% and complete biomass energy recovery in syngas. Unreacted steam is simply condensed out, leading to the production of a syngas with low inert dilution and high calorific value in the range 10.5–12 MJ/Nm3. The syngas produced is rich in hydrogen, exceeding 60% by volume. The proposed process could aid in the transition to a carbon neutral economy as it has the potential to efficiently convert biomass to syngas that can be used for the sustainable generation of fuels, chemicals and energy.

Double synonyms in the genetic code can be used as a tool to test competing hypotheses regarding ambigrammatic narnavirus genomes. Applying the analysis to recent observations of Culex narnavirus 1 and Zhejiang mosquito virus 3 ambigrammatic viruses indicates that the open reading frame on the complementary strand of the segment coding for RNA-dependent RNA polymerase does not code for a functional protein. Culex narnavirus 1 has been shown to possess a second segment, also ambigrammatic, termed ‘Robin’. We find a comparable segment for Zhejiang mosquito virus 3, a moderately diverged relative of Culex narnavirus 1. Our analysis of Robin polymorphisms suggests that its reverse open reading frame also does not code for a functional protein. We make a hypothesis about its role.

Background Current evidence suggests that interval exercise training (IET) and continuous exercise training (CET) produce comparable benefits in exercise capacity, cardiorespiratory fitness and symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the effects of these modalities have only been reviewed in patients with COPD. This meta-analysis compares the effectiveness of IET versus CET on exercise capacity, cardiorespiratory fitness and exertional symptoms in patients with chronic respiratory diseases (CRDs). Methods: PubMed, CINHAL, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and Nursing and Allied health were searched for randomised controlled trials from inception to September 2020. Eligible studies included the comparison between IET and CET, reporting measures of exercise capacity, cardiorespiratory fitness and symptoms in individuals with CRDs. Results: Thirteen randomised control trials (530 patients with CRDs) with fair to good quality on the PEDro scale were included. Eleven studies involved n = 446 patients with COPD, one involved n = 24 patients with cystic fibrosis (CF) and one n = 60 lung transplantation (LT) candidates. IET resulted in greater improvements in peak work rate (WRpeak) (2.40 W, 95% CI: 0.83 to 3.97 W; p = 0.003) and lower exercise-induced dyspnoea (−0.47, 95% CI: −0.86 to 0.09; p = 0.02) compared to CET; however, these improvements did not exceed the minimal important difference for these outcomes. No significant differences in peak values for oxygen uptake (VO2peak), heart rate (HRpeak), minute ventilation (VEpeak), lactate threshold (LAT) and leg discomfort were found between the interventions. Conclusions: IET is superior to CET in improving exercise capacity and exercise-induced dyspnoea sensations in patients with CRDs; however, the extent of the clinical benefit is not considered clinically meaningful.

Exercise intolerance and impaired quality of life (QoL) are characteristic of lung transplant candidates and recipients. This review investigated the effects of exercise training on exercise capacity, QoL and clinical outcomes in pre- and post-operative lung transplant patients.A systematic literature search of PubMed, Nursing and Allied Health, Cochrane (CENTRAL), Scopus and CINAHL databases was conducted from inception until February, 2020. The inclusion criteria were assessment of the impact of exercise training before or after lung transplantation on exercise capacity, QoL or clinical outcomes.21 studies met the inclusion criteria, comprising 1488 lung transplant candidates and 1108 recipients. Studies consisted of five RCTs, two quasi-experimental and 14 single-arm cohort or pilot studies. Exercise training improved or at least maintained exercise capacity and QoL before and after lung transplantation. The impact on clinical outcomes was less clear but suggested a survival benefit. The quality of evidence ranged from fair to excellent.Exercise training appears to be beneficial for patients before and after lung transplantation; however, the evidence for direct causation is limited by the lack of controlled trials. Well-designed RCTs are needed, as well as further research into the effect of exercise training on important post-transplant clinical outcomes, such as time to discharge, rejection, infection, survival and re-hospitalisation.

We analyse the correlation function of the quantum curvature in complex quantum systems, using a random matrix model to provide an exemplar of a universal correlation function. We show that the correlation function diverges as the inverse of the distance at small separations. We also define and analyse a correlation function of mixed states, showing that it is finite but singular at small separations. A scaling hypothesis on a universal form for both types of correlations is supported by Monte-Carlo simulations. We relate the correlation function of the curvature to the variance of Chern integers which can describe quantised Hall conductance., 24 pages, 10 figures, submitted to Sci. Post Physics, minor revision in response to referee reports

Grassland accounts for a high proportion of the agricultural area of the United Kingdom, but the significance of its contribution to the nation’s food supply has been questioned. Using representative figures for the composition of UK ruminant livestock diets, we estimated the total production of human-edible protein from grass and forage crops consumed by cattle and sheep. We found that this equates to 21.5 g of protein per person per day, of which 15.2 g comes from milk, 4.71 g from beef and 1.60 g from sheep meat. This represents 45% of the total amount of human-edible animal protein produced in the UK (46.6 g/head) and is equivalent to one-third of the recommended adult human daily protein intake of 64 g/head. Given the growing pressure to produce food in a more resource-efficient manner, grasslands have a valuable role to play in providing food alongside multiple public goods.

We sought to validate the BDII/Han rat model as a model for diet-induced obesity in endometrial cancer (EC) and determine if transcriptomic changes induced by a high fat diet (HFD) in an EC rat model can be used to identify novel biomarkers in human EC. Nineteen BDII/Han rats were included. Group A (n = 7) were given ad lib access to a normal calorie, normal chow diet (NCD) while Group B (n = 12) were given ad lib access to a calorie rich HFD for 15 months. RNAseq was performed on endometrial tumours from both groups. The top-ranking differentially expressed genes (DEGs) were examined in the human EC using The Cancer Genome Atlas (TCGA) to assess if the BDII/Han rat model is an appropriate model for human obesity-induced carcinogenesis. Weight gain in HFD rats was double the weight gain of NCD rats (50 g vs. 25 g). The incidence of cancer was similar in both groups (4/7&mdash, 57% vs. 4/12&mdash, 33%, p = 0.37). All tumours were equivalent to a Stage 1A, Grade 2 human endometrioid carcinoma. A total of 368 DEGs were identified between the tumours in the HFD group compared to the NCD group. We identified two upstream regulators of the DEGs, mir-33 and Brd4, and a pathway analysis identified downstream enrichment of the colorectal cancer metastasis and ovarian cancer metastasis pathways. Top-ranking DEGs included Tex14, A2M, Hmgcs2, Adamts5, Pdk4, Crabp2, Capn12, Npw, Idi1 and Gpt. A2M expression was decreased in HFD tumours. Consistent with these findings, we found a significant negative correlation between A2M mRNA expression levels and BMI in the TCGA cohort (Spearman&rsquo, s Rho = &minus, 0.263, p &lt, 0.001). A2M expression was associated with improved overall survival (HR = 0.45, 95% CI 0.23&ndash, 0.9, p = 0.024). Crabp2 expression was increased in HFD tumours. In human EC, CRABP2 expression was associated with reduced overall survival (HR = 3.554, 95% CI 1.875&ndash, 6.753, p &lt, 0.001). Diet-induced obesity can alter EC transcriptomic profiles. The BDII/Han rat model is a suitable model of diet-induced obesity in endometrial cancer and can be used to identify clinically relevant biomarkers in human EC.

IntroductionOlder patients undergoing cancer surgery are at increased risk of post-operative complications, prolonged hospital stay, and mortality. Identification of frailty can help predict patients at high risk of peri-operative complications and allow a collaborative, multidisciplinary team approach to their care. A survey was conducted to assess the confidence and knowledge of trainees in obstetrics and gynecology regarding identification and management of peri-operative issues encountered in frail gynecological oncology patients.MethodsA web-based survey was distributed via the Audit and Research in Gynaecological Oncology (ARGO) collaborative and UK Audit and Research Collaborative in Obstetrics and Gynaecology (UKARCOG) . The survey on the management of frail peri-operative patients was disseminated to doctors-in-training (trainees) working in obstetrics and gynecology in the United Kingdom (UK) and Ireland. Specialty (ST1–7), subspecialty, and general practice trainees, non-training grade doctors, and foundation year doctors currently working in obstetrics and gynecology were eligible. Consultants were excluded. Study data were collected using REDCAP software hosted at the University of Manchester. Responses were collected over a 6-week period between January and February 2020.ResultsOf the 666 trainees who participated, 67% (425/666) reported inadequate training in peri-operative management of frail patients. Validated frailty assessment tools were used by only 9% (59/638) of trainees and less than 1% (4/613) were able to correctly identify all the diagnostic features of frailty. Common misconceptions included the use of chronological age and gender in frailty assessments. The majority of trainees (76.5%, 448/586) correctly answered a series of questions relating to mental capacity; however, only 6% (36/606) were able to correctly identify all three diagnostic features of delirium. A total of 87% (495/571) of trainees supported closer collaboration with geriatricians and a multidisciplinary approach.ConclusionsObstetrics and gynecology trainees reported inadequate training in the peri-operative care of frail gynecological oncology patients, and overwhelmingly favored input from geriatricians. Routine use of validated frailty assessment tools may aid diagnosis of frailty in the peri-operative setting. There is an unmet need for formal education in the management of frail surgical patients within the UK and Irish obstetrics and gynecology curriculum.

Background:Resection of intradural spinal tumors typically utilizes a posterior approach and often contributes to significant biomechanical instability and sagittal deformity.Methods:We searched PubMed for studies regarding pre- and postoperative spine biomechanics/alignment in patients with intradural tumors undergoing posterior decompressions.Results:Three patients underwent posterior decompressions with instrumented fusions to preserve good sagittal alignment postoperatively. Variables analyzed in this study included the extent of preoperative and postoperative deformity, the number of surgical levels decompressed and fused, the different frequencies of instability following the resection of cervical versus thoracic versus lumbar lesions, and whether pediatric patients were most likely to develop instability.Conclusion:Simultaneously performing instrumented fusions following posterior spinal decompressions for tumor removal proved optimal in preventing postoperative spinal deformity. Further, “open” surgical procedures offered more optimal/definitive tumor removal versus minimally invasive approaches, and the greater operative exposure and resultant increased risk for instability were remediated by performing simultaneous fusion.

Site identification, site selection, and study start-up have become the focus of improvement by organizations conducting clinical trials.To examine and measure the process from site identification through site activation, Tufts Center for the Study of Drug Development (CSDD) conducted a comprehensive survey among pharmaceutical organizations, biotech companies, and contract research organizations (CROs). Responses from over 400 unique companies were gathered and analyzed.The results indicate that the start-up process is on average 5 to 6 months in total duration, and cycle times across all activities, including site identification, site selection, and study start-up, are faster for repeat sites than for new sites. Comparisons between sponsor and CROs indicate that CROs completed all site-related activities 6 to 11 weeks faster than sponsors. Other areas impacting cycle times were examined, including centralized versus decentralized functions, investment in technology, and organizational strategies that improve cycle time efficiency and performance.Tufts CSDD will explore this area in future research to gather additional insights into other factors that may be associated with speed and efficiency.

This article examines Charles Taylor’s argument that since the 1960s a culture of authenticity has come to define the late modern period. The “age of authenticity” thesis is based on a philosophical and historical approach that follows the development of Romanticism, culminating in the expressive individualism of late modernity. Taylor focuses on the lived experience of secularity and the development of a particular identity that revolves around choice, emotion, and an eclectic approach to religion. Further analysis of Taylor’s work is examined with sociological research on the sacred self and consumption, evangelical and pentecostal appropriation of authenticity, no religion as an option in the age of authenticity, and questions about the search for meaning and purpose.

The effect of textured insoles on kinetics and kinematics of overground running was assessed. 16 male injury-free-recreational runners attended a single visit (age 23 ± 5 yrs; stature 1.78 ± 0.06 m; mass 72.6 ± 9.2 kg). Overground 15-m runs were completed in flat, canvas plimsolls both with and without textured insoles at self-selected velocity on an indoor track in an order that was balanced among participants. Average vertical loading rate and peak vertical force (Fpeak) were captured by force platforms. Video footage was digitised for sagittal plane hip, knee and ankle angles at foot strike and mid stance. Velocity, stride rate and length and contact and flight time were determined. Subjectively-rated plantar sensation was recorded by visual scale. 95% confidence intervals estimated mean differences. Smallest-worthwhile change in loading rate was defined as standardised reduction of 0.54 from a previous comparison of injured versus non-injured runners. Loading rate decreased (-25 to -9.3 BW·s-1; 60% likely beneficial reduction) and plantar sensation was increased (46 to 58 mm) with the insole. Fpeak (-0.1 to 0.14 BW) and velocity (-0.02 to 0.06 m·s-1) were similar. Stride length, flight and contact time were lower (-0.13 to -0.01 m; -0.02 to-0.01 s; -0.016 to -0.006 s) and stride rate was higher (0.01 to 0.07 steps·s-1) with insoles. Textured insoles elicited an acute, meaningful decrease in vertical loading rate in short-distance, overground running and were associated with subjectively-increased plantar sensation. Reduced vertical loading rate could be explained by altered stride characteristics.

Background The phenomenon of internet dependence has changed the way the rising generation seeks information. This mentality has caused medical students to turn to online resources as they seek information about potential residency training programs. Residency program web presence (PWP) is increasingly important, and may even impact recruitment efforts. Improvement of PWP could enhance programs' recruitment of ideal candidates. Objectives The purpose of this study is to assess how ophthalmology residency PWP is impacting the residency recruitment process by understanding how it influences applicants' application and rank list choices as well as to identify the contributing factors. Methods Applicants applying for ophthalmology residency training at Penn State University during the 2015–2016 and 2016–2017 application cycles were surveyed using Research Electronic Data Capture (REDCap). Surveys sought applicants' perspectives with respect to their experiences with PWP and how those experiences shaped their application and rank list decisions. Results Of 860 applicants, 214 (24.9%) responded, accounting for 17.4% (214/1,228) of all ophthalmology residency applicants during the respective cycles; 72.4% of respondents expressed PWP does impact where they apply, how they form their rank list, or both; 93.4% said websites are an important resource during the application process; 47.2% conveyed interest in programs utilizing social media tools; and 76.5% of respondents felt websites gave sufficient information less than 50% of the time. Conclusion Ophthalmology PWP does impact resident recruitment. By enhancing program websites and adding social media tools, programs can improve recruitment efforts.

SWENSON, Don. Alleluia: An Ethnographic Study. Lanham, MD: Lexington Books, 2018. 165pp. Hbk. ISBN: 9781498546638. £60.

The case for grazing dairy cows at pasture is reviewed in six categories: (i) optimal land use for food production; (ii) soil carbon sequestration; (iii) carbon footprint; (iv) animal health and welfare; (v) effects on human health of milk produced from grazed pasture; and (vi) consumer demand for milk from grazed cows. Land best-suited to grazing is uncultivatable peaty soil receiving relatively low levels of fertilisation. With soil carbon sequestration, carbon footprint is lower for grazing than for other systems of milk production. Some indices of animal health and welfare (e.g., lameness, status of hock integument) are influenced positively by extent of grazing. Benefits to human health may accrue from higher levels of essential amino acids, carotenoids, omega-3 fatty acids and conjugated linoleic acid in milk from cows given pasture compared to diets based on silage and concentrates. Milk producers, processors and supermarkets are responding to consumer demand for milk and milk products from cows given access to pasture during the grazing season. The major constraint to milk production from grazing is energy intake. Research opportunities to address this constraint include application of remote sensing and artificial intelligence to grazing management.

Background Novel methods in predicting survival in patients with spinal metastases may help guide clinical decision-making and stratify treatments regarding surgery vs palliative care. Objective To evaluate whether the frailty/sarcopenia paradigm is predictive of survival and morbidity in patients undergoing surgery for spinal metastasis. Methods A total of 271 patients from 4 tertiary care centers who had undergone surgery for spinal metastasis were identified. Frailty/sarcopenia was defined by psoas muscle size. Survival hazard ratios were calculated using multivariate analysis, with variables from demographic, functional, oncological, and surgical factors. Secondary outcomes included improvement of neurological function and postoperative morbidity. Results Patients in the smallest psoas tertile had shorter overall survival compared to the middle and largest tertile. Psoas size (PS) predicted overall mortality more strongly than Tokuhashi score, Tomita score, and Karnofsky Performance Status (KPS). PS predicted 90-d mortality more strongly than Tokuhashi score, Tomita score, and KPS. Patients with a larger PS were more likely to have an improvement in deficit compared to the middle tertile. PS was not predictive of 30-d morbidity. Conclusion In patients undergoing surgery for spine metastases, PS as a surrogate for frailty/sarcopenia predicts 90-d and overall mortality, independent of demographic, functional, oncological, and surgical characteristics. The frailty/sarcopenia paradigm is a stronger predictor of survival at these time points than other standards. PS can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.

Introduction: The incidence of endometrial cancer (EC) is rising - a consequence of the current obesity epidemic. An improved understanding of obesity-induced EC is needed to manage this growing cohort of patients. Here-in we present Cellular Retinoic Acid Binding Protein 2 (CRABP2), which was identified as an obesity-related gene in the BDII/Han rat spontaneous EC model, as a novel biomarker in high-risk EC. Methods:BDII/Han rats were fed either a high (N=12) or low calorie (N=7) diet for 15 months. RNA-seq, - differential gene expression and gene set enrichment analysis (GSEA) were performed on endometrial tumors from both groups. The association between CRABP2 mRNA expression and standard clinico-pathological features was examined in human EC using the TCGA. Following dichotomization of patients based on their CRABP2 mRNA expression using regression tree analysis, univariate and multivariate Cox regression survival analyses were performed. Differential gene expression analysis and GSEA were performed on human tumors stratified according to CRABP2 expression levels. In-silico findings were validated using immunohistochemistry (IHC) assessing CRABP2 expression in normal endometrium, primary and metastatic endometrial carcinoma. Results:Weight gain in high fat diet (HFD) rats was double that of normal chow diet rats (50 g vs. 25 g). The incidence of cancer was similar in both groups (4/7-57% vs. 4/12-33%; p=0.37). 368 differentially expressed genes (DEGs) were identified between both groups. CRABP2 was upregulated in tumors from the HFD group. Regression tree analysis identified 60 (11%) tumors in the TCGA with increased CRABP2 mRNA expression. Increased CRABP2 expression was associated with serous EC (p Conclusion: A HFD increased CRABP2 expression in rat EC. In humans, increased expression of CRABP2 is associated with high-risk EC. Transcriptomic analysis and validation using IHC suggests that CRABP2 and retinoic acid signalling may be an important therapeutic target in advanced EC. Citation Format: Donagh Egan, Bruce Moran, Michael Wilkinson, William Gallagher, Xavier Matias-Guiu, Walter Kolch, Carel LeRoux, Donal Brennan. CRABP2 - a novel biomarker for high risk endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 658.

It is conceivable that an RNA virus could use a polysome, that is, a string of ribosomes covering the RNA strand, to protect the genetic material from degradation inside a host cell. This paper discusses how such a virus might operate, and how its presence might be detected by ribosome profiling. There are two possible forms for such a polysomally protected virus, depending upon whether just the forward strand or both the forward and complementary strands can be encased by ribosomes (these will be termed type 1 and type 2, respectively). It is argued that in the type 2 case the viral RNA would evolve an ambigrammatic property, whereby the viral genes are free of stop codons in a reverse reading frame (with forward and reverse codons aligned). Recent observations of ribosome profiles of ambigrammatic narnavirus sequences are consistent with our predictions for the type 2 case., 14 pages, 4 figures, Physical Biology, in press

Purpose: Postoperative hemoglobin (Hb) determination remains an essential parameter for quantifying blood loss following total knee replacement (TKR) surgery and guiding transfusion practice. In this study we aimed to ascertain the optimal timing for Hb determination postoperatively and assess its relationship to serum hematocrit (Hct). Materials and Methods: This was a retrospective cohort analysis of 61 consecutive patients undergoing preoperative, day 1 and day 2 Hb and Hct concentration determination following TKR surgery. This was a single centre study in the United Kingdom. Results: The mean fall in Hb concentration at day 1 was 2.9 g/dL in comparison to 3.3 g/dL at day 2. This indicated a significant difference of 0.39 g/dL (p=0.023). A total of 5 patients required blood transfusions following day 2 Hb determination. Postoperative Hct values varied in close relation with the Hb concentration with no significant differences demonstrated. Our study reveals a significant change between day 1 and day 2 Hb concentrations following TKR surgery, with no significant differing information provided through Hct determination. Conclusions: Our results support the use of delayed routine testing at day 2 following surgery as it is likely to more accurately reflect ongoing hidden blood loss into the joint cavity and within soft tissue planes.

Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery from ischemic stroke. Understanding the role of endogenous neural stem and progenitor cells under normal physiological conditions aids in analyzing their effects after ischemic injury, including their impact on functional recovery and neurogenesis at the site of injury. Recent animal studies have utilized unique subsets of exogenous and endogenous stem cells as well as preconditioning with pharmacologic agents to better understand the best situation for stem cell proliferation, migration, and differentiation. These stem cell therapies provide a promising effect on stimulation of endogenous neurogenesis, neuroprotection, anti-inflammatory effects, and improved cell survival rates. Clinical trials performed using various stem cell types show promising results to their safety and effectiveness on reducing the effects of ischemic stroke in humans. Another important aspect of stem cell therapy discussed in this review is tracking endogenous and exogenous NSCs with magnetic resonance imaging. This review explores the pathophysiology of NSCs on ischemic stroke, stem cell therapy studies and their effects on neurogenesis, the most recent clinical trials, and techniques to track and monitor the progress of endogenous and exogenous stem cells.

Introduction/Background HIPEC improves overall survival in patients with stage III epithelial ovarian cancer after neoadjuvant therapy compared to interval cytoreductive surgery (CRS) alone. The immediate impact of HIPEC on the systemic immune response has not been well characterised. We sought to document the impact of cisplatin-based HIPEC on the systemic immune response. Methodology Longitudinal analysis of neutrophil to lymphocyte ratio (NLR) and monocyte to neutrophil ratio (MLR) results in 22 age and stage matched patients with stage IIIc EOC were examined. Flow cytometric analysis (FACs) was performed on intra-operative PBMCs before and after HIPEC in 3 patients. Independent sample t test and one way ANOVA was used to analyse results using SPPS version 24. Results 9 patients had primary CRS, 8 had interval CRS+ cisplatin HPEC (50 mg/m2 at 40°C for 60 min), and 5 had interval CRS with no HIPEC. All patients had aggressive CRS and an CC0 resection. The interval CRS (no HIPEC) group had a significantly lower day 1 NLR compared to interval CRS HIPEC group (p=0.047). The NLR of all groups was similar by day 4. The MLR in the three groups was similar at all time points. FACs of peripheral CD3+ T Cells demonstrated that HIPEC increased circulating CD8+ T Cells and reduced expression of the immune checkpoint protein TIGIT (p Conclusion Cisplatin-based HIPEC causes an rapid and short-lived change in the systemic immune response. Our initial findings that HIPEC alters the expression of immune checkpoint proteins on CD8+ T cells suggests that further investigations of the combination of HIPEC and immunotherapy may be warranted. Disclosure Nothing to disclose.

Hierarchical image representation is multiscale decomposition of images which is proven very useful in automated faint astronomical source detection from optical images. Hierarchical image representation is typically done using tree data structure (i.e. max-tree), whose computational cost of construction highly depends on the resolution and the dynamic range of image. Efficient and fast tree construction is crucial here because the amount of optical imaging data is increasing exponentially, and the upcoming new giant telescopes such as European Extremely Large Telescope (E-ELT) will produce even more images. Here we investigate some of the recent developments in tree construction algorithms and optimization techniques that have significantly increased its computation speed.

The sheet-like endoplasmic reticulum (ER) of eukaryotic cells has been found to be riddled with spiral dislocations, known as ‘Terasaki ramps’, in the vicinity of which the doubled bilayer membranes which make up ER sheets can be approximately modeled by helicoids. Here we analyze diffusion on a surface with locally helicoidal topological dislocations, and use the results to argue that the Terasaki ramps facilitate a highly efficient transport of water-soluble molecules within the lumen of the endoplasmic reticulum.