Associations between perceived discrimination and contraceptive method use: why we need better measures of discrimination in reproductive healthcare.

Discrimination has historically contributed to coercive contraceptive in the United States. We investigated associations between perceived discrimination, or the perception of unequal treatment in everyday life, and contraceptive method use among U.S. women. We analyzed population-based data from a 2013 study of U.S. women who were premenopausal, age 18-50, sexually active with a male partner in the last year and were not attempting pregnancy. Perceived discrimination was measured using the Everyday Discrimination Scale. Contraceptive method use was categorized into five method categories: permanent, highly effective reversible, moderately effective, barrier and no method. We analyzed relationships between perceived discrimination and contraceptive method use with several regression models, controlling for covariates. Among 539 women in our analytic sample, those with high perceived discrimination had lower incomes, less educational attainment and were less likely to be insured. Perceived discrimination was associated with a reduced odds of using any contraceptive method (aOR 0.43, CI 0.21-0.87, p < .001). Contraceptive method users with high perceived discrimination had an increased odds of using highly effective reversible methods versus moderately effective methods (aOR 5.28, CI 1.63-17.07 p = < .001). Women who perceived discrimination were at risk for contraceptive nonuse; however, among contraceptive users, perceived discrimination was associated with the use of more effective reversible methods.

The Effective Management of Idiopathic Intracranial Hypertension Delivered by In-person and Virtual Group Consultations: Results and Reflections from a Phase One Service Delivery.

The increasing incidence of idiopathic intracranial hypertension (IIH) with the obesity epidemic is leading to increased pressures on service capacity. Evidence shows that group consultations (GCs) deliver effective, person-centred healthcare, but the feasibility for IIH is unknown. We set out to develop and test a safe and effective GC service for IIH. Through an interactive approach, we co-designed a bespoke in-person and virtual GC model, where patients are reviewed in a group setting. Improvements were made following each session following patient input and team reflections. Outcomes measured included patient satisfaction, self-perceived health literacy, and successful implementation of the GCs. During the pilot, eight in-person GCs were delivered: once-monthly (Oct-Dec 2019), then twice-monthly (Jan-Feb 2020). Feedback was received from 49/53 patients. 100% felt more satisfied and heard, 100% felt more involved in decision-making, 98% had a better understanding of their condition, 96% felt more able to cope with their condition and keep themselves healthy, 94% rated this as a positive experience, and 90% reported improved access and more time with their clinician compared with existing 1:1 appointments. Since September 2020, in response to the COVID-19 pandemic, we transitioned to weekly virtual GCs, receiving overwhelmingly positive feedback (median scores: patient satisfaction 9.5/10; being listened to by clinician 10/10; involved by clinician in treatment decisions 10/10; clinician explanation of treatment 10/10; and opportunity to discuss condition or treatment 10/10). GCs are safe and effective for IIH, and preferred in our patient cohort. This allowed ongoing high-quality, person-centred care despite challenges from the COVID-19 pandemic.

Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network.

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.

Suppression of decoherence tied to electron-phonon coupling in telecom-compatible quantum dots: low-threshold reappearance regime for quantum state inversion.

We demonstrate suppression of dephasing tied to deformation potential coupling of confined electrons to longitudinal acoustic (LA) phonons in optical control experiments on large semiconductor quantum dots (QDs) with emission compatible with the low-dispersion telecommunications band at 1.3 µm. By exploiting the sensitivity of the electron-phonon spectral density to the size and shape of the QD, we demonstrate a fourfold reduction in the threshold pulse area required to enter the decoupled regime for exciton inversion using adiabatic rapid passage (ARP). Our calculations of the quantum state dynamics indicate that the symmetry of the QD wave function provides an additional means to engineer the electron-phonon interaction. Our findings will support the development of solid-state quantum emitters in future distributed quantum networks using semiconductor QDs.

Genotype and risk of tumour rupture in gastrointestinal stromal tumour.

BACKGROUND: Tumour rupture is a strong predictor of poor outcome in gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The objective was to determine whether tumour genotype was associated with risk of rupture. METHODS: Rupture was classified according to the definition proposed by the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively for all patients at Oslo University Hospital undergoing surgery for localized GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger sequencing. RESULTS: Two hundred and nine patients with mutation data available were identified. Tumour rupture occurred in 37 patients. Among the 155 patients with KIT exon 11 mutations, an increased risk of rupture was observed with a deletion or insertion-deletion (25 of 86, 29 per cent) compared with substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per cent) (P = 0·014). Notably, rupture occurred in 17 of 46 tumours (37 per cent) with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13·8 per cent) with other exon 11 mutations (P = 0·002). This association was confined to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of 77 (8 per cent) with other exon 11 mutations (P = 0·001). In multivariable logistic regression analysis, del557/558 and tumour size were associated with an increased likelihood of tumour rupture, but mitotic count was not. CONCLUSION: Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at increased risk of tumour rupture. This high-risk feature can be identified in the diagnostic evaluation and should be included in the assessment when neoadjuvant imatinib treatment is considered.

A quantitative analysis of statistical power identifies obesity end points for improved in vivo preclinical study design.

The design of well-powered in vivo preclinical studies is a key element in building the knowledge of disease physiology for the purpose of identifying and effectively testing potential antiobesity drug targets. However, as a result of the complexity of the obese phenotype, there is limited understanding of the variability within and between study animals of macroscopic end points such as food intake and body composition. This, combined with limitations inherent in the measurement of certain end points, presents challenges to study design that can have significant consequences for an antiobesity program. Here, we analyze a large, longitudinal study of mouse food intake and body composition during diet perturbation to quantify the variability and interaction of the key metabolic end points. To demonstrate how conclusions can change as a function of study size, we show that a simulated preclinical study properly powered for one end point may lead to false conclusions based on secondary end points. We then propose the guidelines for end point selection and study size estimation under different conditions to facilitate proper power calculation for a more successful in vivo study design.

Cyprinid herpesvirus 3 as a potential biological control agent for carp (Cyprinus carpio) in Australia: susceptibility of non-target species.

Carp (Cyprinus carpio L.) is a pest species in Australian waterways, and cyprinid herpesvirus 3 (CyHV-3) is being considered as a potential biological control (biocontrol) agent. An important consideration for any such agent is its target specificity. In this study, the susceptibility to CyHV-3 of a range of non-target species (NTS) was tested. The NTS were as follows: 13 native Australian, and one introduced, fish species; a lamprey species; a crustacean; two native amphibian species (tadpole and mature stages); two native reptilian species; chickens; and laboratory mice. Animals were exposed to 100-1000 times the approximate minimum amount of CyHV-3 required to cause disease in carp by intraperitoneal and/or bath challenge, and then examined clinically each day over the course of 28 days post-challenge. There were no clinical signs, mortalities or histological evidence consistent with a viral infection in a wide taxonomic range of NTS. Furthermore, there was no molecular evidence of infection with CyHV-3, and, in particular, all RT-PCRs for viral mRNA were negative. As a consequence, the results encourage further investigation of CyHV-3 as a potential biocontrol agent that is specific for carp.

Sublethal effects of angling and release on golden perch Macquaria ambigua: implications for reproduction and fish health.

The present study tested the hypothesis of no delayed sublethal effects of mild angling and release on the feeding, growth, somatic condition and gonadal development of golden perch Macquaria ambigua during gametogenesis. Subsamples of adult M. ambigua (n = 17-21 of 207), originally captured from the wild and stocked into ten 0·1 ha earthen ponds, were angled and released during early and late gametogenesis. Wild samples that were concurrently collected throughout the experiment underwent rapid and synchronous gonadal development and many spawned. While no spawning occurred in the ponds, most M. ambigua underwent normal gonadal development to maturity, including the angled fish. Angled fish also fed, maintained condition and actually grew faster than non-angled captive controls. Although females that were angled during late gametogenesis more readily ingested and retained baited hooks, neither their subsequent condition nor gonadal development was significantly affected. The predominance of null results was attributed to the combined effects of the flexible reproductive strategy of M. ambigua, the benignness of mouth hooking and immediate release, and possible methodological issues arising from differential hooking success of more aggressive and resilient individuals. The findings support earlier catch-and-release research, but contrast with reports of acute reproductive effects following capture and handling for aquaculture broodstock. This discrepancy highlights the need for research to specifically address welfare questions relevant to recreational fisheries across various species and angling scenarios.

Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.

Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function. A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04). There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions.

Definition and clinical significance of tumour rupture in gastrointestinal stromal tumours of the small intestine.

BACKGROUND: Tumour rupture is a risk factor for recurrence of gastrointestinal stromal tumour (GIST). In this study, patterns of recurrence after potential tumour seeding were investigated, and a new definition of tumour rupture, based on major and minor defects of tumour integrity, is proposed. METHODS: Patients undergoing surgery for non-metastatic small intestinal GIST from 2000 to 2012 were included in the study. Tumour spillage, tumour fracture or piecemeal resection, bowel perforation at the tumour site, blood-tinged ascites, microscopic tumour infiltration into an adjacent organ, and surgical biopsy were defined as major defects of tumour integrity. Peritoneal tumour penetration, iatrogenic peritoneal laceration and microscopically involved margins were defined as minor defects. RESULTS: Seventy-two patients were identified. Median follow-up was 58 (range 7-122) months. Radical surgery was performed in 71 patients. A major defect was recorded in 20 patients, and a minor defect in 21. The 5-year recurrence rate was 64, 29 and 31 per cent in patients with major, minor and no defect respectively (P = 0·001). The hazard ratio (HR) for major defect versus no defect was 3·55 (95 per cent c.i. 1·51 to 8·35). Peritoneal recurrence rates for major, minor and no defect were 52, 25 and 19 per cent respectively (P = 0·002), and the HR for major defect versus no defect was 4·98 (1·69 to 14·68). On multivariable analysis, mitotic index, major defect of tumour integrity, tumour size and age were independently associated with risk of recurrence. CONCLUSION: Recurrence rates were increased after major, but not minor tumour ruptures.

Increasing the frequency of physical activity very brief advice by nurses to cancer patients. A mixed methods feasibility study of a training intervention.

OBJECTIVES: To examine the impact, acceptability, practicability and implementation of a training intervention, designed using the Behaviour Change Wheel, on the delivery of very brief advice on physical activity, by nurses to cancer patients. STUDY DESIGN: A mixed methods feasibility study. METHOD: A purposeful sample of nurses (n = 62) were recruited across two delivery arms, face-to-face (n = 55) and online (n = 7). Frequency of delivery of physical activity advice was collected at baseline with follow-up at 12 weeks. The 'capability, opportunity and motivation' of nurses to deliver very brief advice was measured via questionnaire. Semi-structured phone interviews (n = 14) were completed and analyzed thematically. A cost consequence analysis was undertaken. RESULTS: The intervention improved the 'capability, opportunity and motivation' of nurses resulting in a change in knowledge, attitudes and beliefs towards physical activity. The intervention was both acceptable and practical. Face-to-face was the preferred mode of delivery, however there was also value in the online option. The cost of delivery per participant was £33.87 for face-to-face delivery, and £103.83 for online delivery inflated due to low recruitment numbers. A significant improvement was seen in delivery of very brief advice at 12 weeks (Z = -4.39, P ≤ 0.01). CONCLUSION: The intervention is acceptable, practical and improves delivery of very brief advice on physical activity by nurses to cancer patients in the short-term. Both face-to-face and online delivery should be considered.

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate.

Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX). MTX is an analog of folate, which is essential for DNA synthesis. Genetic polymorphism at single nucleotide can be indicative to the prognostic outcome in patients. Germ-line variants in candidate genes, coding for enzymes active in the metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly better survival in comparison with patients having the AA genotype (P=0.046). These patients also had a lower frequency of metastasis (15%, P=0.029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line variants in the MTX metabolic pathway are associated with survival and side effects in patients treated with MTX.

Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior.

The obesity epidemic is believed to be driven by a food environment that promotes consumption of inexpensive, convenient, high-calorie, palatable foods. Individual differences in obesity susceptibility or resistance to weight loss may arise because of alterations in the neurocircuitry supporting food reward and eating habits. In particular, dopamine signaling in the ventromedial striatum is thought to encode food reward and motivation, whereas dopamine in the dorsal and lateral striatum orchestrates the development of eating habits. We measured striatal dopamine D2-like receptor binding potential (D2BP) using positron emission tomography with [(18)F]fallypride in 43 human subjects with body mass indices (BMI) ranging from 18 to 45 kg m(-)(2). Opportunistic eating behavior and BMI were both positively associated with D2BP in the dorsal and lateral striatum, whereas BMI was negatively associated with D2BP in the ventromedial striatum. These results suggest that obese people have alterations in dopamine neurocircuitry that may increase their susceptibility to opportunistic overeating while at the same time making food intake less rewarding, less goal directed and more habitual. Whether or not the observed neurocircuitry alterations pre-existed or occurred as a result of obesity development, they may perpetuate obesity given the omnipresence of palatable foods and their associated cues.

Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis.

OBJECTIVES: Until recently, reports of physical activity in rheumatoid arthritis (RA) were limited to self-report methods and/or leisure-time physical activity. Our objectives were to assess, determine correlates of, and compare to well-matched controls both exercise and sedentary time in a typical clinical cohort of RA. METHOD: Persons with established RA (seropositive or radiographic erosions; n = 41) without diabetes or cardiovascular disease underwent assessments of traditional and disease-specific correlates of physical activity and 7 days of triaxial accelerometry. Twenty-seven age, gender, and body mass index (BMI)-matched controls were assessed. RESULTS: For persons with RA, objectively measured median (25th-75th percentile) exercise time was 3 (1-11) min/day; only 10% (n = 4) of participants exercised for ≥ 30 min/day. Time spent in sedentary activities was 92% (89-95%). Exercise time was not related to pain but was inversely related to disease activity (r = -0.3, p < 0.05) and disability (r = -0.3, p < 0.05) and positively related to self-efficacy for endurance activity (r = 0.4, p < 0.05). Sedentary activity was related only to self-efficacy for endurance activity (r = -0.4, p < 0.05). When compared to matched controls, persons with RA exhibited poorer self-efficacy for physical activity but similar amounts of exercise and sedentary time. CONCLUSIONS: For persons with RA and without diabetes or cardiovascular disease, time spent in exercise was well below established guidelines and activity patterns were predominantly sedentary. For optimal care in RA, in addition to promoting exercise, clinicians should consider assessing sedentary behaviour and self-efficacy for exercise. Future interventions might determine whether increased self-efficacy can increase physical activity in RA.

Spatial organization and coordination of slow waves in the mouse anorectum.

The internal anal sphincter (IAS) develops tone and is important for maintaining a high anal pressure while tone in the rectum is less. The mechanisms responsible for tone generation in the IAS are still uncertain. The present study addressed this question by comparing the electrical properties and morphology of the mouse IAS and distal rectum. The amplitude of tone and the frequency of phasic contractions was greater in the IAS than in rectum while membrane potential (Em) was less negative in the IAS than in rectum. Slow waves (SWs) were of greatest amplitude and frequency at the distal end of the IAS, declining in the oral direction. Dual microelectrode recordings revealed that SWs were coordinated over a much greater distance in the circumferential direction than in the oral direction. The circular muscle layer of the IAS was divided into five to eight 'minibundles' separated by connective tissue septa whereas few septa were present in the rectum. The limited coordination of SWs in the oral direction suggests that the activity in adjacent minibundles is not coordinated. Intramuscular interstitial cells of Cajal and platelet-derived growth factor receptor alpha-positive cells were present in each minibundle suggesting a role for one or both of these cells in SW generation. In summary, three important properties distinguish the IAS from the distal rectum: (1) a more depolarized Em; (2) larger and higher frequency SWs; and (3) the multiunit configuration of the muscle. All of these characteristics may contribute to greater tone generation in the IAS than in the distal rectum.

ENCCA WP17-WP7 consensus paper on teenagers and young adults (TYA) with bone sarcomas.

Teenagers and young adults (TYA) cancer contributes substantially to morbidity and mortality in a population with much to offer society. TYA place distinct challenges upon cancer care services, many reporting feeling marginalized and their needs not being met in adult or paediatric cancer services. Bone tumours such as osteosarcoma and Ewing sarcoma, because of their age at presentation and the complexity of their care, are where challenges in managing (TYA) with cancer have often been most readily apparent. Bone sarcomas may be managed by paediatric or medical oncologists, and require fastidious attention to protocol. A lack of recent improvement in survival in TYA with bone tumours may be linked to a lack of specialist care, poor concordance with therapy in some situations and TYA-specific pharmacology. Participation in clinical trials, particularly of young adults, is low, hindering progress. All these requirements may be best met by a concerted effort to create collaborative care between adult and paediatric experts in bone sarcoma, working together to meet TYA patients' needs.

Deep brain stimulation for obsessive-compulsive disorder: a systematic review and meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) is increasingly being applied to psychiatric conditions such as obsessive-compulsive disorder (OCD), major depression and anorexia nervosa. Double-blind, randomized controlled trials (RCTs) of active versus sham treatment have been limited to small numbers. We therefore undertook a systematic review and meta-analysis of the effectiveness of DBS in psychiatric conditions to maximize study power. METHOD: We conducted a systematic literature search for double-blind, RCTs of active versus sham treatment using Pubmed/Medline and EMBASE up to April 2013. Where possible, we combined results from studies in a meta-analysis. We assessed differences in final values between the active and sham treatments for parallel-group studies and compared changes from baseline score for cross-over designs. RESULTS: Inclusion criteria were met by five studies, all of which were of OCD. Forty-four subjects provided data for the meta-analysis. The main outcome was a reduction in obsessive symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS). Patients on active, as opposed to sham, treatment had a significantly lower mean score [mean difference (MD) -8.93, 95% confidence interval (CI) -13.35 to -5.76, p < 0.001], representing partial remission. However, one-third of patients experienced significant adverse effects (n = 16). There were no differences between the two groups in terms of other outcomes. CONCLUSIONS: DBS may show promise for treatment-resistant OCD but there are insufficient randomized controlled data for other psychiatric conditions. DBS remains an experimental treatment in adults for severe, medically refractory conditions until further data are available.

Clinical signs of barotrauma in golden perch, Macquaria ambigua (Richardson), and associated effects on post-release mortality and health.

This study assessed the effects of different retrieval depths (2, 10 or 20 m), surface intervals (none or 15 min) and release methods (untreated, vented or recompressed) on the incidence of external and internal clinical signs of barotrauma (ECSB and ICSB) and post-release mortality in golden perch, Macquaria ambigua (Richardson). Fish were assessed for ECSB before and after surface intervals and either monitored for mortality over 3 days in two deep cages or killed for internal examination. When all fish were left untreated, short-term mortality increased with retrieval depth from 0% and 4.2% among 2 and 10-m fish, respectively, to 19.2% among 20-m fish; while surface interval only affected the incidence of two ECSB (excess buoyancy and a prolapsed cloaca). Mortality was also greater among 20-m fish that were subjected to a 15-min surface interval and left untreated (22.2%) or vented (22.2%) than those that were recompressed (5.6%). Of the ECSB, only exophthalmia was associated with increased mortality, with half of the affected fish dying. However, many fish retrieved from 10 and 20 m also sustained numerous ICSB, including compressed gonads or vital organs and ruptured or collapsed, haemorrhaging swimbladders that remained deflated for up to 3 days after release.