Effects of resistance exercise, collagen ingestion and circulating oestrogen concentration on collagen synthesis in a female athlete: A case report.

We investigated the effects of resistance exercise (RE), hydrolysed collagen (HC) ingestion and circulating oestrogen concentration on collagen synthesis in a naturally menstruating female CrossFit athlete. In a double-blind, randomised cross-over design, the participant (36 years; height 1.61 m; mass 82.6 kg) consumed 0 or 30 g HC prior to performing back-squat RE when endogenous circulating oestrogen concentration was low (onset of menses, OM) and high (late follicular phase, LF) during two consecutive menstrual cycles. Ten 5-mL blood samples were collected during each of the four interventions to analyse concentrations of serum 17ß-oestradiol, and biomarkers of type I collagen turnover, that is serum procollagen type I N-terminal propeptide (PINP, a biomarker of collagen synthesis) and plasma ß-isomerised C-terminal telopeptide of type I collagen (ß-CTX, a biomarker of collagen breakdown), as well as the serum concentration of 18 collagen amino acids. 17ß-Oestradiol concentration was 5-fold higher at LF (891 ± 116 pmol L-1) than OM (180 ± 13 pmol L-1). The PINP concentration × time area under the curve (AUC) was higher in the 30 g HC OM intervention (201 µg L-1 h) than the 30 g HC LF (144 µg L-1 h), 0 g HC OM (151 µg L-1 h) and 0 g HC LF (122 µg L-1 h) interventions. ß-CTX concentration decreased 1.4-fold from pre-RE to 6 h post-RE in all interventions. Thus, high circulating oestrogen concentration was associated with lower collagen synthesis following RE in this female athlete. Ingesting 30 g HC, however, augmented the collagen synthesis response at LF and particularly at OM. HIGHLIGHTS: What is the central question of this study? Does resistance exercise-induced collagen synthesis vary according to circulating oestrogen concentration in a naturally menstruating female athlete, and if so, does hydrolysed collagen ingestion have any impact? What is the main finding and its importance? Exercise-induced collagen synthesis was low when circulating oestrogen concentration was high and vice versa. However, ingesting 30 g hydrolysed collagen prior to exercise reduced the negative effect of oestrogen on collagen synthesis. As high circulating oestrogen has been associated with greater injury risk in females, supplementing exercise with hydrolysed collagen may help protect these tissues from injury.

Interactive voice response (IVR) for tobacco cessation: a systematic review.

OBJECTIVE: To summarise the uses, outcomes and implementation of interactive voice response (IVR) as a tobacco cessation intervention. DATA SOURCES: A systematic review was conducted. Searches were performed on 3 May 2023. The strategies used keywords such as "tobacco cessation", "smoking reduction" and "interactive voice recording". Ovid MEDLINE ALL, Embase, APA PsycINFO, CINAHL, Cochrane Library and Web of Science were searched. Grey literature searches were also conducted. STUDY SELECTION: Titles and abstracts were assessed by two independent reviewers. Studies were included if IVR was an intervention for tobacco cessation for adults; any outcomes were reported and study design was comparative. Any abstract included by either reviewer proceeded to full-text review. Full texts were reviewed by two independent reviewers. DATA EXTRACTION: Data were independently extracted by two reviewers using a standardised form. The Risk of Bias Tool for Randomised Trials and the Risk of Bias in Non-Randomised Studies of Interventions tools were used to assess study quality. DATA SYNTHESIS: Of 308 identified abstracts, 20 moderate-quality to low-quality studies were included. IVR was used standalone or adjunctly as a treatment, follow-up or risk-assessment tool across populations including general smokers, hospitalised patients, quitline users, perinatal women, patients with cancer and veteran smokers. Effective studies found that IVR was delivered more frequently with shorter follow-up times. Significant gaps in the literature include a lack of population diversity, limited implementation settings and delivery schedules, and limited patient and provider perspectives. CONCLUSIONS: While the evidence is weak, IVR appears to be a promising intervention for tobacco cessation. However, pilot programmes and research addressing literature gaps are necessary.

Collagen peptide supplementation before bedtime reduces sleep fragmentation and improves cognitive function in physically active males with sleep complaints.

PURPOSE: The primary aim of this study was to examine whether a glycine-rich collagen peptides (CP) supplement could enhance sleep quality in physically active men with self-reported sleep complaints. METHODS: In a randomized, crossover design, 13 athletic males (age: 24 ± 4 years; training volume; 7 ± 3 h·wk1) with sleep complaints (Athens Insomnia Scale, 9 ± 2) consumed CP (15 g·day1) or a placebo control (CON) 1 h before bedtime for 7 nights. Sleep quality was measured with subjective sleep diaries and actigraphy for 7 nights; polysomnographic sleep and core temperature were recorded on night 7. Cognition, inflammation, and endocrine function were measured on night 7 and the following morning. Subjective sleepiness and fatigue were measured on all 7 nights. The intervention trials were separated by ≥ 7 days and preceded by a 7-night familiarisation trial. RESULTS: Polysomnography showed less awakenings with CP than CON (21.3 ± 9.7 vs. 29.3 ± 13.8 counts, respectively; P = 0.028). The 7-day average for subjective awakenings were less with CP vs. CON (1.3 ± 1.5 vs. 1.9 ± 0.6 counts, respectively; P = 0.023). The proportion of correct responses on the baseline Stroop cognitive test were higher with CP than CON (1.00 ± 0.00 vs. 0.97 ± 0.05 AU, respectively; P = 0.009) the morning after night 7. There were no trial differences in core temperature, endocrine function, inflammation, subjective sleepiness, fatigue and sleep quality, or other measures of cognitive function or sleep (P > 0.05). CONCLUSION: CP supplementation did not influence sleep quantity, latency, or efficiency, but reduced awakenings and improved cognitive function in physically active males with sleep complaints.

Quality of New Domestic Hand Sanitizer Drug Product Manufacturers During COVID-19.

The FDA initiated a cross-sectional, statistically based sampling and testing study to characterize the quality of marketed alcohol-based hand sanitizer (ABHS) by evaluating the alcohol content and impurities present in ABHS products manufactured by establishments that registered with the FDA during March-April 2020. A stratified sampling design divided the population of manufacturers into independent groups based on each establishment's level of experience with FDA oversight and its geographic location. ABHS products were collected and analyzed by spatially offset Raman spectroscopy and gas chromatography with mass spectrometry (GC-MS). The GC-MS results for 310 products, from 196 newly registered domestic manufacturers, showed that 71.6% (± 5.7%) of these manufacturers had violative products. In 104 (33.5%) cases, the alcohol content did not meet label claim assay specifications but still fell within CDC efficacy ranges. Ethanol ABHS products failed more often overall (assay and impurities) (84.3%) and for impurities (84.3%), than isopropanol ABHS products (11.2% and 6.2%, respectively). Differences in test results across active ingredients were statistically significant. Ethanol ABHS products often (63.5% of cases) failed due to the presence of acetal or acetaldehyde, particularly in products with pH ≤ 6. Other impurities were also detected in several ABHS products, suggesting the use of low-grade alcohol in the manufacture of these products. Evidence was insufficient to conclude that having experience manufacturing FDA-regulated products, or lack thereof, influenced product-level violative results. This study highlights the importance of sourcing and testing active pharmaceutical ingredients to produce quality drug products.

The Collagen Synthesis Response to an Acute Bout of Resistance Exercise Is Greater when Ingesting 30 g Hydrolyzed Collagen Compared with 15 g and 0 g in Resistance-Trained Young Men.

BACKGROUND: Resistance exercise (RE) stimulates collagen synthesis in skeletal muscle and tendon but there is limited and equivocal evidence regarding an effect of collagen supplementation and exercise on collagen synthesis. Furthermore, it is not known if a dose-response exists regarding the effect of hydrolyzed collagen (HC) ingestion and RE on collagen synthesis. OBJECTIVE: To determine the HC dose-response effect on collagen synthesis after high-intensity RE in resistance-trained young men. METHODS: Using a double-blind, randomized crossover design, 10 resistance-trained males (age: 26 ± 3 y; height: 1.77 ± 0.04 m; mass: 79.7 ± 7.0 kg) ingested 0 g, 15 g, or 30 g HC with 50 mg vitamin C 1 h before performing 4 sets' barbell back squat RE at 10-repetition maximum load, after which they rested for 6 h. Blood samples were collected throughout each of the 3 interventions to analyze procollagen type Ⅰ N-terminal propeptide (PINP) and ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX) concentration, and the concentration of 18 collagen amino acids. RESULTS: The serum PINP concentration × time area under the curve (AUC) was greater for 30 g (267 ± 79 µg·L-1·h) than for 15 g (235 ± 70 µg·L-1·h, P = 0.013) and 0 g HC (219 ± 88 µg·L-1·h, P = 0.002) but there was no difference between 0 and 15 g HC (P = 0.225). The AUCs of glycine and proline were greater for 30 g than for 15 and 0 g HC (P < 0.05). Plasma ß-CTX concentration decreased from -1 to +6 h (P < 0.05), with no differences between interventions. CONCLUSIONS: Ingesting 30 g HC before high-intensity RE augments whole-body collagen synthesis more than 15 g and 0 g HC in resistance-trained young males.

Promotion of physical activity among people who identify as women through the ParticipACTION mobile app.

OBJECTIVE: Health and fitness mobile applications can increase users' physical activity (PA) levels (Lister et al., 2014). ParticipACTION is a national non-profit organization that developed a mobile app to target PA among adults (Truelove et al., 2020). The aim of this research was to examine how women's PA is related to their use of the ParticipACTION app. METHODS AND MEASUREMENT: Using a mixed-methods design, participants (n = 3,493) completed a survey regarding their PA levels, motivation for PA (capability, opportunity, motivation; COM-B, Keyworth et al., 2020), and motivation for using the ParticipACTION app. Nine focus groups were conducted (n = 37) to discuss the mobile app further. RESULTS: Path analyses revealed that users' app use was positively associated with motivations for various app functions (e.g. self-monitoring, seeking exercise guidance), however, only motivation in-turn predicted PA. Descriptive results indicated that many women in Canada who used the app do not meet national guidelines for PA per week. Qualitative findings highlight women's motivation for using the app, concerns with app functionality, and feelings of guilt for not engaging in PA. CONCLUSION: The ParticipACTION app may have some benefit for improving women's PA; intervention studies are needed to determine efficacy of mobile applications.

New specimens of middle Eocene omomyines (Primates, Omomyoidea) from the Uinta Basin of Utah and the Tornillo Basin of Texas, with clarification of the generic status of Ourayia, Mytonius, and Diablomomys.

In the middle Eocene, multiple lineages of North American omomyoids independently evolved body masses greater than 500 g. Most of these large-bodied omomyoids are known from small sample sizes, which has contributed to a lack of consensus regarding their alpha taxonomy. Here, we describe new Uintan omomyine specimens from the Uinta Basin of Utah and the Tornillo Basin of Texas. These new samples expand the hypodigms of Diablomomys dalquesti, Mytonius hopsoni, and Ourayia uintensis, and favor the recognition of new species of Mytonius and Ourayia based on specimens from the Tornillo Basin. These samples support the recognition of Diablomomys as a valid genus distinct from Omomys, Ourayia as a valid genus distinct from Macrotarsius, and Mytonius as a valid genus distinct from Ourayia. Although Diablomomys and Omomys co-occur in the late Uintan of the Tornillo Basin, Ourayia and Mytonius are time-successive taxa with a wide distribution across multiple Laramide basins. The data presented here reinforce the conclusion that the Uintan was a time period in which omomyines diversified to include a large number of taxa with body masses above Kay's threshold and frugivorous-folivorous diets. These data also provide evidence that North American primate faunas exhibited a shifting pattern of regional endemism during the middle Eocene. By the early Uintan, primate faunas from Southern California were already quite distinct from primate faunas of the central Rocky Mountains or Trans-Pecos Texas. By the late Uintan, primate faunas in all three regions demonstrated greater provincialism, with Trans-Pecos Texas and Southern California both exhibiting a large number of endemic primate taxa and sharing only a single primate genus (Macrotarsius) in common. This increase in primate endemism across the Uintan may be tied to changes in paleohabitats associated with the larger trend toward decreasing temperatures from the Early Eocene Climatic Optimum to the Eocene/Oligocene transition.

Fact or Fiction? The Development and Evaluation of a Tobacco Virtual Health Tool.

The virtual setting is an important setting for health promotion as individuals increasingly go online for health information and support. Yet, users can have difficulty finding valid, trustworthy, and user-friendly health information online. In 2022, we launched an interactive Fact or Fiction Tobacco virtual health tool. The virtual health tool uses evidence-informed tailored content to engage users and refer them to local tobacco cessation resources. The present paper describes the development, user testing, and evaluation of this tool. The Fact or Fiction virtual health tool was designed by tobacco cessation and health marketing experts and informed by health behaviour theories of change. The tool captures data on who is seeking health information, the user's stage of readiness to quit tobacco products, and whether they act by accessing referred resources. In 2021, we conducted two phases of user testing prior to marketing the tool publicly. After 7 weeks of marketing, we collected data on user interactions with the tool and evaluated the reach of the tool. Results from user testing found the tool to be engaging, easy to use, and quick to complete. Adaptations were made to simplify and condense text and include additional animations. During the first seven weeks of the tool being live, it reached 2306 users, and 38.7% of those users were current or occasional tobacco users. Users were classified based on their intention to quit. Bivariate analysis found that the tool was successful in driving tobacco users towards action as 21.2% tobacco users who were looking to quit and 8.8% of tobacco users who were not looking to quit clicked on local tobacco cessation resources. This virtual health tool is reaching the targeted population and providing tailored information needed at each stage of the continuum of health behaviour change. Among tobacco users looking to quit, this virtual health tool acts as a quick referral to local tobacco cessation resources.

The effects of collagen peptides on exercise-induced gastrointestinal stress: a randomized, controlled trial.

PURPOSE: We examined the effects of collagen peptides (CP) supplementation on exercise-induced gastrointestinal (GI) stress. METHODS: In a randomized, crossover design, 20 volunteers (16 males: [Formula: see text]O2max, 53.4 ± 5.9 ml·kg-1) completed 3 trials: a non-exercise rest trial, with no supplement (REST) and then an exercise trial with CP (10 g·day-1) or placebo control (CON) supplements, which were consumed for 7 days prior to, and 45 min before, a 70 min run at 70-90% of [Formula: see text]O2max. Outcome measures included urinary lactulose and rhamnose (L/R), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), anti-LPS antibody, monocyte-chemoattractant protein-1 (MCP-1), interleukin (IL) 6 and 8, cortisol, alkaline phosphatase (ALP) (measured pre, 10 min post and 2 h post) and subjective GI symptoms. RESULTS: There were no differences in heart rate, perceived exertion, thermal comfort, or core temperature during exercise in the CP and CON trials (all P > 0.05). I-FABP was higher in CP (2538 ± 1221 pg/ml) and CON (2541 ± 766 pg/ml) vs. REST 2 h post (1893 ± 1941 pg/ml) (both P < 0.05). LPS increased in CON vs. REST 2 h post (+ 71.8 pg/ml; P < 0.05). Anti-LPS antibody decreased in CON and CP vs. REST at post (both P < 0.05). There were no differences in MCP-1, IL-6, and IL-8 between the CP and CON trials (all P > 0.05), and no differences in L/R or GI symptoms between CON and CP (all P > 0.05). CONCLUSION: Collagen peptides did not modify exercise-induced changes in inflammation, GI integrity or subjective GI symptoms but LPS was higher in CON 2 h post-exercise and thus future studies may be warranted.

Spontaneous resolution of syringomyelia following pregnancy and parturition in a patient with type I chiari malformation: A case and systematic review.

BACKGROUND: Spontaneous resolution of syringomyelia has rarely been reported in the literature. Rarer still are cases wherein this process is associated with pregnancy and parturition. We review theories on syringomyelia development and spontaneous resolution to better understand the role pregnancy and parturition may play in both processes. METHODS: We present a 30-year-old female with MRI-confirmed spontaneous syrinx regression following caesarean delivery of a full-term pregnancy. We additionally review the literature to identify previously reported cases of spontaneous syrinx regression both independent of and associated with pregnancy. RESULTS: Including the present case, 39 cases describing spontaneous regression of syringomyelia have been reported in the literature, of which only four are associated with pregnancy and parturition. 75% of all reported cases were associated with type I Chiari malformation, though several disorders of the craniocervical junction and spinal canal were implicated. Complete syrinx regression was achieved in 33.3% of cases and 5% of cases described recurrence of syringomyelia following the spontaneous resolution. CONCLUSION: Syringomyelia likely develops due to disturbance of the physiologic flow of cerebrospinal fluid around the craniocervical junction and the obex. Several mechanisms including fissuring of the spinal cord parenchyma and reduction of subarachnoid scarring are likely involved in this process. In the setting of pregnancy, additional mechanisms surrounding the increased intraabdominal forces imparted by a growing fetus, Valsalva-like strain experienced during labor, and hemodynamic changes that occur to accommodate gestation are likely implicated. Nevertheless, patients should continue to be monitored periodically for syrinx recurrence.

iCn3D: From Web-Based 3D Viewer to Structural Analysis Tool in Batch Mode.

iCn3D was initially developed as a web-based 3D molecular viewer. It then evolved from visualization into a full-featured interactive structural analysis software. It became a collaborative research instrument through the sharing of permanent, shortened URLs that encapsulate not only annotated visual molecular scenes, but also all underlying data and analysis scripts in a FAIR manner. More recently, with the growth of structural databases, the need to analyze large structural datasets systematically led us to use Python scripts and convert the code to be used in Node. js scripts. We showed a few examples of Python scripts at https://github.com/ncbi/icn3d/tree/master/icn3dpython to export secondary structures or PNG images from iCn3D. Users just need to replace the URL in the Python scripts to export other annotations from iCn3D. Furthermore, any interactive iCn3D feature can be converted into a Node. js script to be run in batch mode, enabling an interactive analysis performed on one or a handful of protein complexes to be scaled up to analysis features of large ensembles of structures. Currently available Node. js analysis scripts examples are available at https://github.com/ncbi/icn3d/tree/master/icn3dnode. This development will enable ensemble analyses on growing structural databases such as AlphaFold or RoseTTAFold on one hand and Electron Microscopy on the other. In this paper, we also review new features such as DelPhi electrostatic potential, 3D view of mutations, alignment of multiple chains, assembly of multiple structures by realignment, dynamic symmetry calculation, 2D cartoons at different levels, interactive contact maps, and use of iCn3D in Jupyter Notebook as described at https://pypi.org/project/icn3dpy.

Muscular anatomy of the forelimb of tiger (Panthera tigris).

Dissection reports of large cats (family Felidae) have been published since the late 19th century. These reports generally describe the findings in words, show drawings of the dissection, and usually include some masses of muscles, but often neglect to provide muscle maps showing the precise location of bony origins and insertions. Although these early reports can be highly useful, the absence of visual depictions of muscle attachment sites makes it difficult to compare muscle origins and insertions in living taxa and especially to reconstruct muscle attachments in fossil taxa. Recently, more muscle maps have been published in the primary literature, but those for large cats are still limited. Here, we describe the muscular anatomy of the forelimb of the tiger (Panthera tigris), and compare muscle origins, insertions, and relative muscle masses to other felids to identify differences that may reflect functional adaptations. Our results reiterate the conservative nature of felid anatomy across body sizes and behavioral categories. We find that pantherines have relatively smaller shoulder muscle masses, and relatively larger muscles of the caudal brachium, pronators, and supinators than felines. The muscular anatomy of the tiger shows several modifications that may reflect an adaptation to terrestrial locomotion and a preference for large prey. These include in general a relatively large m. supraspinatus (shoulder flexion), an expanded origin for m. triceps brachii caput longum, and relatively large m. triceps brachii caput laterale (elbow extension), as well as relatively large mm. brachioradialis, abductor digiti I longus, and abductor digiti V. Muscle groups that are well developed in scansorial taxa are not well developed in the tiger, including muscles of the cranial compartment of the brachium and antebrachium, and m. anconeus. Overall, the musculature of the tiger strongly resembles that of the lion (Panthera leo), another large-bodied terrestrial large-prey specialist.

Catch-down growth in infants born large for gestational age.

Infants born large for gestational age (LGA) not exhibiting catch-down growth (a decline of weight z-score by 1) have a higher likelihood of future obesity. We aimed to identify the term LGA infants in our neonatal intensive care unit (NICU) and document nutrition interventions that may influence growth. Our 10-year retrospective review identified 47 term LGA infants who had a NICU length of stay (LOS) ≥7 days. We obtained demographic data, nutrition interventions in the NICU, and data regarding growth patterns. Of the 47 infants, 31 (66%), demonstrated catch-down growth at discharge at ≥7 days. Overall, 39 of 47 patients (83%) received interventions during their NICU stay, including 32 (69%) who had nasogastric tubes placed, and 24 (51%) had formula fortification to augment weight gain. Among patients with LOS ≥14 days, 23 of 23 patients without catch-down growth and four of five patients with catch-down growth had nutrition interventions performed. Of the overall population, only 38% of those who did not demonstrate catch-down growth had an LOS of ≥14 days vs 77% of all infants that did exhibit catch-down growth (P = .01). Our data suggest that nutrition interventions in LGA infants are common in the NICU. Our study highlights the need for further clinical studies to help direct care in this population of infants.

Brexit: A Boon or a Curse for Animals Used in Scientific Procedures?

The UK has long been hailed as one of the world leaders in animal welfare. Within the UK, animals used in experiments are provided some protection under the Animals (Scientific Procedures) Act 1986 (ASPA). This Act was impacted by European Union (EU) Directive 2010/63/EU, and subsequently the ASPA was updated to reflect any changes required. While the Directive is very similar to the protection the UK already afforded to animals used in experiments, there were some advances that the Directive provided that were not present in the ASPA. On paper, the changes introduced were promising but may not have been achieved in practice. In 2016, the British public voted to leave the EU, which presented concerns over animal welfare protection and legislation provided by EU law. With the completion of Brexit, there may be an opportunity to diverge from the Directive to advance protection for animals used in experiments. This article explores the influence that the EU has had on animal experimentation in the UK, the potential implications of Brexit on the welfare of animals used in experiments and suggests ways in which this protection can be progressed, with potentially more freedom to amend or introduce legislation to do so.

Real-world efficacy, tolerability, and safety of ubrogepant.

OBJECTIVE: To assess the real-world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center. BACKGROUND: The efficacy and safety of ubrogepant for the acute treatment of migraine were established in phase 3 randomized controlled trials. However, there is no real-world data of patient experience with ubrogepant in a population in which the majority of patients have chronic migraine, multiple prior unsuccessful treatments, complex medical comorbidities, and concurrent use of other migraine-specific medications. METHOD: This was a post-market cohort study conducted at Mayo Clinic Arizona. All patients prescribed ubrogepant were tracked and contacted 1-3 months after the prescription to answer a list of standardized questions. Demographic information and additional headache history were obtained from chart review. RESULTS: We obtained eligible questionnaire responses from 106 patients. Chronic migraine accounted for 92/106 (86.8%) of the population. Complete headache freedom (from mild/moderate/severe to no pain) and headache relief (from moderate/severe to mild/no pain or mild to no pain) for ≥75% of all treated attacks at 2 hours after taking ubrogepant were achieved in 20/105 (19.0%) and 50/105 (47.6%) patients, respectively. A total of 33/106 (31.1%) patients reported being "very satisfied" with ubrogepant. Adverse events were reported in 42/106 (39.6%) patients, including fatigue in 29/106 (27.4%), dry mouth in 8/106 (7.5%), nausea/vomiting in 7/106 (6.6%), constipation in 5/106 (4.7%), dizziness in 3/106 (2.8%), and other adverse events in 7/106 (6.6%). Predictive factors for being a "good responder" to ubrogepant, defined as headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant, included migraine with aura, episodic migraine, <5 prior unsuccessful preventive or acute treatment trials. Additionally, prior treatment responses to a CGRP monoclonal antibody and onabotulinumtoxinA injections are predictive of treatment responses and patient satisfaction to ubrogepant. For the 62/106 (58.5%) patients concurrently using a CGRP monoclonal antibody, there was no difference in the "good responder" rate or adverse event rate compared to those who were not on a CGRP monoclonal antibody, though the rate of moderate, as opposed to mild adverse events was higher, 11/62 (47.8%) versus 3/44 (17.6%), p = 0.048. Additionally, 16 patients had a history of significant cardiovascular or cerebrovascular diseases. No severe adverse events were reported in any patient. CONCLUSION: Our study confirms and extends the efficacy profile and tolerability of ubrogepant in a real-world tertiary headache clinic and identifies factors that may predict efficacy. Adverse event rates were higher than reported in clinical trials. Further studies are needed to confirm these findings and to evaluate the long-term efficacy and safety of ubrogepant.

Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol.

INTRODUCTION: Patients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months. METHODS AND ANALYSIS: ETHICS AND DISSEMINATION: This study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.

A 'Life-Style Choice' or a Philosophical Belief?: The Argument for Veganism and Vegetarianism to be a Protected Philosophical Belief and the Position in England and Wales.

The recent judgment in Casamitjana Costa v The League Against Cruel Sports in England and Wales held that ethical veganism was a protected philosophical belief under employment law. In contrast, vegetarianism was found not to be a protected philosophical belief in Conisbee v Crossley Farms Limited and others. The authors argue that the Employment Tribunal misunderstood the notion of vegetarianism when deciding that it was a 'life-style choice'. There are different kinds of vegans and vegetarians, each with their own way of practising the philosophy which influences how they live their life. Not all people who follow a meat-free diet should be afforded this protection, and it depends on whether their belief is one which is determined by certain factors, such as animal welfare and environmentalism, rather than for health purposes. The authors explore the arguments and analysis in the above employment cases, coming to the conclusion that the tribunals oversimplified what it means to hold values such as veganism and vegetarianism, failing to understand the differences between different classifications and sub-groups when coming to a decision. The different kinds of vegans and vegetarians and their characteristics are outlined, before determining whether this should constitute protection under employment law, protecting individuals from discrimination. The situation in the USA and Canada regarding this issue is very different, and there are parallels drawn with attempting to establish veganism or vegetarianism as a religion, and where they could benefit from the recent decision in England and Wales. Finally, this paper concludes that ethical and environmental veganism and vegetarianism should both qualify as protected philosophical beliefs, but other kinds may fall short of what is required to satisfy the requirements under law.

Failure of national antenatal vitamin D supplementation programme puts dark skinned infants at highest risk: A newborn bloodspot screening study.

OBJECTIVES: To determine the prevalence of vitamin D deficiency on dried blood spots (DBS) obtained at newborn blood spot screening (NBS) and thereby test the efficacy of the UK national antenatal supplementation programme in an increasingly ethnically diverse English population. To evaluate the seasonal and ethnic variation in neonatal plasma 25 hydoxyvitamin D (25OHD) and its determinants. DESIGN: Three thousand random DBS samples received at a single regional newborn screening laboratory (52° N) over two one-week periods, one in winter (February 2019) and one in summer (August 2019), were collected. Data was collected from NBS cards on birth weight, gestational age, maternal age, ethnicity, and post code which was replaced with index of multiple deprivation (IMD). 25OHD concentrations were measured on 6 mm sub-punch from DBS using quantitative liquid chromatography tandem mass spectrometry adjusted to equivalent plasma values. 25OHD variation with season was assessed using Mann-Whitney U test and ethnic groups compared using Kruskal-Wallis test. Linear regression was used to assess the determinants of 25OHD concentrations. RESULTS: 25OHD measurements were available in 2999 (1580 males) subjects [1499 winter-born and 1500 summer-born]. The majority were white British (59.1%) and born at term (mean ± SD gestational age of 38.8 ± 1.8 weeks) with a mean (±SD) birth weight of 3306 (±565) grams. The overall prevalence of vitamin D deficiency [25OHD<30 nmol/L (12 µg/L)] was 35.7% (n = 1070) and insufficiency [30-50 nmol/L (12-20 µg/L)] 33.7% (n = 1010). The median (IQR) 25OHD concentration was significantly lower in the winter-born compared to summer-born [29.1 (19.8, 40.6) vs 49.2 (34.3, 64.8) nmol/L respectively; p < 0.001]. Across both seasons, when compared to white British babies (41.6 nmol/L), the median 25OHD concentrations were significantly lower in babies of black (30.3 nmol/L; p < 0.001), Asian (31.3 nmol/L; p < 0.001), any other mixed (32.9 nmol/L; p < 0.001), mixed white and black (33.7 nmol/L; p < 0.05) and any other white (37.7 nmol/L; p < 0.05) ethnicity. The proportion of deficiency was also higher in babies of Asian (48%), black (47%) and mixed ethnicity (38-44%) compared to any other white (34%) or white British (30%) ethnicity. Season of birth, ethnicity, gestation and maternal age accounted for almost 24% of the variation in 25OHD concentrations. CONCLUSION: The current UK antenatal supplementation programme fails to protect newborns from vitamin D deficiency, especially those from minority ethnic groups who are at high risk of vitamin D deficiency. Nearly 70% of all newborns and 85% of winter-borns had 25OHD concentrations below 50 nmol/L (20 µg/L). Almost 50% of babies of Black or Asian origin were deficient at birth, which explains their high risk of hypocalcaemic complications and rickets if left unsupplemented. Our findings call for an immediate review of the delivery of antenatal and infant vitamin D supplementation programmes and implementation of food fortification in the long term.

Forensic Tools for Species Identification of Skeletal Remains: Metrics, Statistics, and OsteoID.

Although nonhuman remains constitute a significant portion of forensic anthropological casework, the potential use of bone metrics to assess the human origin and to classify species of skeletal remains has not been thoroughly investigated. This study aimed to assess the utility of quantitative methods in distinguishing human from nonhuman remains and present additional resources for species identification. Over 50,000 measurements were compiled from humans and 27 nonhuman (mostly North American) species. Decision trees developed from the long bone data can differentiate human from nonhuman remains with over 90% accuracy (>98% accuracy for the human sample), even if all long bones are pooled. Stepwise discriminant function results were slightly lower (>87.4% overall accuracy). The quantitative models can be used to support visual identifications or preliminarily assess forensic significance at scenes. For species classification, bone-specific discriminant functions returned accuracies between 77.7% and 89.1%, but classification results varied highly across species. From the study data, we developed a web tool, OsteoID, for users who can input measurements and be shown photographs of potential bones/species to aid in visual identification. OsteoID also includes supplementary images (e.g., 3D scans), creating an additional resource for forensic anthropologists and others involved in skeletal species identification and comparative osteology.

Ecomorphological variation in artiodactyl calcanei using 3D geometric morphometrics.

Artiodactyl postcrania are commonly used as paleoecological indicators but these studies are usually limited to artiodactyls within a single family. Here, we use 3D geometric morphometrics to analyze the morphology of calcanei from five artiodactyl families (Antilocapridae, Bovidae, Cervidae, Giraffidae, and Tragulidae) and identify common ecological trends among these families using principal component analysis. Our results indicate that antilocaprid and some bovid calcanei show convergent evolution of cursorial morphology and that other bovids have independently evolved less cursorial morphology that is more similar to cervids. This study shows that parallel ecomorphological trends can be identified in multiple families of artiodactyls, as well as within artiodactyl groups. This further suggests that the calcaneus may be a good indicator of ecology and function in fossil groups that are taxonomically ambiguous or not closely related to living taxa.