Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England.

BACKGROUND: We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome. METHODS: Data were extracted from Public Health England's National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses. RESULTS: Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65-79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years. CONCLUSIONS: Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

BACKGROUND: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. OBJECTIVES: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. METHODS: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. RESULTS: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. CONCLUSIONS: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

The resilience of the developing reading system: multi-modal evidence of incident and recovery after a pediatric stroke.

Decades of neuroscientific findings have elucidated the highly specialized brain areas involved in reading, especially along the ventral occipitotemporal stream where the critical step of recognizing words occurs. We report on a 14-year-old female with temporary dyslexia after a left ventral occipitotemporal ischemic stroke. Our longitudinal multimodal findings show that the resolution of the reading impairment was associated with heightened activity in the left posterior superior and inferior temporal gyri. Our findings highlight the role of the left inferior temporal gyrus in reading and the importance of perilesional and ipsilateral cortical areas for functional recovery after childhood stroke.

Quality assessment of cancer patient education materials: the current state of systemic therapy patient education in fourteen cancer centres across Ontario, Canada.

PURPOSE: Most patients diagnosed with cancer are administered systemic therapy and these patients are counselled and given printed education (PE) materials. High rates of low health literacy highlight the need to evaluate the quality of these PE materials. METHODS: A current state assessment of the quality of PE materials was conducted in Ontario, Canada. Patient education leaders from 14 cancer centres submitted print materials on the topic of systemic cancer therapy to the assessment team. To report adherence to PE quality and health literacy best practices, the following validated measures were used: readability (FRY, SMOG and Flesch Reading Ease), understandability and actionability (Patient Education Materials Assessment Tool (PEMAT)). Materials at grade level 6 or lower and with PEMAT scores greater than 80% were considered to meet health literacy best practices. RESULTS: A total of 1146 materials were submitted; 366 met inclusion criteria and 83 were selected for assessment. Most materials scored below the 80% target for understandability (x̄ = 73%, 31-100%) and actionability (x̄ = 68%, 20-100%), and above the recommended grade 6 readability level (x̄ = grade 9) meaning that the majority did not meet quality standards or best practices. CONCLUSION: Results suggest that there is significant opportunity to improve the quality of PE materials distributed by cancer centres. The quality of PE materials is a critical safety and equity consideration when these materials convey important safety and self-care directives.

Contamination in complex healthcare trials: the falls in care homes (FinCH) study experience.

BACKGROUND: Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants. CONCLUSION: Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise.

Provincial Veterinary Services respond to drought in South Africa.

In 2018, Cape Town, South Africa, nearly ran out of water. That this has not yet happened is in large part due to the water-saving efforts of its citizens. It is highly likely that this situation will be repeated in Cape Town and that similar situations will be experienced by major cities in other parts of the world. Efforts to save water should thus continue and the lessons learned in Cape Town should be shared. The functioning of Veterinary Services during a drought is affected in the same way as any business, in terms of running an office, but veterinary professionals face an increased risk of exposure to pathogens, compared to that of many occupations, and of veterinary officials becoming disease vectors. One component of Veterinary Services is veterinary laboratory services. Laboratory procedures rely heavily on water and, without advance planning, a laboratory's function can be severely limited by a restricted water supply. In many cases, innovative water-saving techniques can be used to reduce water use substantially without compromising the quality of the services offered. Here, the authors share their experiences and some lessons learned while working in Veterinary Services in the Western Cape province of South Africa.

En 2018, la ville du Cap en Afrique du Sud a failli manquer d'eau. Si la pénurie totale a pu être évitée, ce fut en grande partie grâce aux efforts déployés par les habitants pour économiser l'eau. Or, il est très probable que cette situation se reproduise au Cap et que des situations analogues surviennent dans nombre de grandes métropoles d'autres régions du monde. C'est pourquoi il convient de poursuivre les efforts d'économie d'eau et de partager avec d'autres les enseignements tirés dans la ville du Cap. L'impact de la sécheresse sur le fonctionnement des Services vétérinaires est similaire à celui de toute organisation en termes de gestion administrative ; en revanche, par rapport à d'autres professionnels, les vétérinaires de terrain sont davantage exposés à des agents pathogènes et au risque de devenir eux-mêmes vecteurs de maladies. Les laboratoires vétérinaires sont l'une des composantes des Services vétérinaires. Les procédures de laboratoire sont amplement tributaires de l'eau ; or, en l'absence d'une planification préalable, les activités d'un laboratoire pourraient être gravement mises à mal par des restrictions de l'approvisionnement en eau. Dans bien des cas, il est possible d'utiliser des techniques innovantes pour économiser l'eau afin d'en diminuer la consommation sans pour autant compromettre la qualité des services rendus. Les auteurs font part de leur expérience et de certains enseignements tirés lorsqu'ils travaillaient dans les Services vétérinaires de la province du Cap-Occidental en Afrique du Sud.

En 2018 faltó poco para que Ciudad del Cabo (Sudáfrica) se quedara sin agua. Si las cosas aún no han llegado a este extremo es, en gran parte, gracias a los esfuerzos de los habitantes por economizar agua. Es muy probable que en el futuro Ciudad del Cabo vuelva a sufrir esta situación y que grandes metrópolis de otras partes del mundo conozcan dificultades parecidas. Por ello hay que perseverar en los esfuerzos de ahorro de agua y se deben compartir las enseñanzas extraídas en Ciudad del Cabo. Durante una sequía, el funcionamiento de los Servicios Veterinarios se ve afectado del mismo modo que cualquier otra actividad, por lo que respecta al trabajo de oficina, pero además los profesionales del ramo, en comparación con los de otros muchos sectores, corren mayor peligro de exposición a patógenos, lo que a su vez entraña el riesgo de que los propios veterinarios ejerzan de vectores de la enfermedad. Uno de los puntales de los Servicios Veterinarios son los laboratorios veterinarios, cuyo quehacer depende en gran medida del uso de agua. Por ello, cuando no se ha planificado con antelación la eventualidad de una penuria de agua, esta puede imponer graves cortapisas a las funciones de laboratorio. En muchos casos es posible emplear innovadoras técnicas de ahorro de agua para reducir sustancialmente las cantidades utilizadas sin menoscabo de la calidad de los servicios dispensados. Los autores comparten su experiencia y algunas de las lecciones que extrajeron de su trabajo en los Servicios Veterinarios de la provincia sudafricana del Cabo Occidental.

Impact of intended and relative dose intensity of R-CHOP in a large, consecutive cohort of elderly diffuse large B-cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age.

BACKGROUND: The increasing incidence of diffuse large B-cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co-morbidity, frailty, and reduced organ and physiological reserve contribute to treatment-related complications. The optimal dose intensity of R-CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. OBJECTIVES AND METHODS: We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009-2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. RESULTS: Porgression-free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70-79 years (P < 0.001). In contrast, 2-year cumulative relapse incidence, when accounting for non-relapse mortality as a competing risk, was no different between 70-79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS-G: 0-6 vs. >6) (P = 0.27). In 70-79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70-79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). CONCLUSION: 'R-mini-CHOP' provides adequate lymphoma-specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.

Accuracy of tele-consultation on management decisions of lesions suspect for melanoma using reflectance confocal microscopy as a stand-alone diagnostic tool.

BACKGROUND: Diagnostic accuracy of reflectance confocal microscopy (RCM) as a stand-alone diagnostic tool for suspect skin lesions has not been extensively studied. OBJECTIVE: Primary aim was to measure experts' accuracy in RCM-based management decisions. Secondary aim was to identify melanoma-specific RCM features. METHODS: The study enrolled patients ≥18 years that underwent biopsy of skin lesions clinically suspected to be melanoma. One hundred lesions imaged by RCM were randomly selected from 439 lesions prospectively collected at four pigmented lesion clinics. The study data set included 23 melanomas, three basal cell and two squamous cell carcinomas, 11 indeterminate melanocytic lesions and 61 benign lesions including 50 nevi. Three expert RCM evaluators were blinded to clinical or dermoscopic images, and to the final histopathological diagnosis. Evaluators independently issued a binary RCM-based management decision, 'biopsy' vs. 'observation'; these decisions were scored against histopathological diagnosis, with 'biopsy' as the correct management decision for malignant and indeterminate lesions. A subset analysis of 23 melanomas and 50 nevi with unequivocal histopathological diagnosis was performed to identify melanoma-specific RCM features. RESULTS: Sensitivity, specificity and diagnostic accuracy were 74%, 67% and 70% for reader 1, 46%, 84% and 69% for reader 2, and 72%, 46% and 56% for reader 3, respectively. The overall kappa for management decisions was 0.34. Readers had unanimous agreement on management for 50 of the 100 lesions. Non-specific architecture, non-visible papillae, streaming of nuclei, coarse collagen fibres and abnormal vasculature showed a significant association with melanoma in the evaluation of at least two readers. CONCLUSIONS: Reflectance confocal microscopy tele-consultation of especially challenging lesions, based on image review without benefit of clinical or dermoscopy images, may be associated with limited diagnostic accuracy and interobserver agreement. Architectural and stromal criteria may emerge as potentially useful and reproducible criteria for melanoma diagnosis.

Empowering Women Researchers in the New Century: IADR's Strategic Direction.

Gender inequality in science, medicine, and dentistry remains a central concern for the biomedical research workforce today. Although progress in areas of inclusivity and gender diversity was reported, growth has been slow. Women still face multiple challenges in reaching higher ranks and leadership positions while maintaining holistic success in these fields. Within dental research and academia, we might observe trends toward a more balanced pipeline. However, women continue to face barriers in seeking leadership roles and achieving economic equity and scholarship recognition. In an effort to evaluate the status of women in dental research and academia, the authors examined the role of the International Association for Dental Research (IADR), a global research organization, which has improved awareness on gender inequality. The goal of this article is to review five crucial issues of gender inequality in oral health research and academics-workforce pipeline, economic inequality, workplace harassment, gender bias in scholarly productivity, and work-life balance-and to discuss proactive steps that the IADR has taken to promote gender equality. Providing networking and training opportunities through effective mentoring and coaching for women researchers, the IADR has developed a robust pipeline of women leaders while promoting gender equality for women in dental academia through a culture shift. As knowledge gaps remained on the levels of conscious and unconscious bias and sexist culture affecting women advancement in academics, as well as the intersectionality of gender with race, gender identity, ability status, sexual orientation, and cultural backgrounds, the IADR has recognized that further research is warranted.

Gender Inequalities in the Dental Workforce: Global Perspectives.

The aim of this review is to investigate the growth of diversity and inclusion in global academic dental research with a focus on gender equality. A diverse range of research methodologies were used to conduct this review, including an extensive review of the literature, engagement of key informants in dental academic leadership positions around the world, and review of current data from a variety of national and international organizations. Results provide evidence of gender inequalities that currently persist in dental academics and research. Although the gender gap among graduating dental students in North America and the two most populous countries in Europe (the United Kingdom and France) has been narrowed, women make up 30% to 40% of registered dentists in countries throughout Europe, Oceania, Asia, and Africa. In academic dentistry around the globe, greater gender inequality was found to correlate with higher ranking academic and leadership positions in the United States, United Kingdom, several countries in European Union, Japan, and Saudi Arabia. Further disparities are noted in the dental research sector, where women make up 33% of dental researchers in the European Union, 35% in North America, 55% in Brazil, and 25% in Japan. Family and societal pressures, limited access to research funding, and lack of mentoring and leadership training opportunities are reported as also contributing to gender inequalities. To continue advancing gender equality in dental academia and research, efforts should be geared toward the collection and public dissemination of data on gender-specific distributions. Such evidence-driven information will guide the selection of future strategies and best practices for promoting gender equity in the dental workforce, which provides a major pipeline of researchers and scholars for the dental profession.

Factors associated with long-term weight-loss maintenance following bariatric surgery in adolescents with severe obesity.

BACKGROUND/OBJECTIVES: Bariatric surgery produces robust weight loss, however, factors associated with long-term weight-loss maintenance among adolescents undergoing Roux-en-Y gastric bypass surgery are unknown. SUBJECTS/METHODS: Fifty adolescents (mean±s.d. age and body mass index (BMI)=17.1±1.7 years and 59±11 kg m-2) underwent Roux-en-Y gastric bypass surgery, had follow-up visits at 1 year and at a visit between 5 and 12 years following surgery (Follow-up of Adolescent Bariatric Surgery at 5 Plus years (FABS-5+) visit; mean±s.d. 8.1±1.6 years). A non-surgical comparison group (n=30; mean±s.d. age and BMI=15.3±1.7 years and BMI=52±8 kg m-2) was recruited to compare weight trajectories over time. Questionnaires (health-related and eating behaviors, health responsibility, impact of weight on quality of life (QOL), international physical activity questionnaire and dietary habits via surgery guidelines) were administered at the FABS-5+ visit. Post hoc, participants were split into two groups: long-term weight-loss maintainers (n=23; baseline BMI=58.2 kg m-2; 1-year BMI=35.8 kg m-2; FABS-5+ BMI=34.9 kg m-2) and re-gainers (n=27; baseline BMI=59.8 kg m-2; 1-year BMI=36.8 kg m-2; FABS-5+ BMI=48.0 kg m-2) to compare factors which might contribute to differences. Data were analyzed using generalized estimating equations adjusted for age, sex, baseline BMI, baseline diabetes status and length of follow-up. RESULTS: The BMI of the surgical group declined from baseline to 1 year (-38.5±6.9%), which, despite some regain, was largely maintained until FABS-5+ (-29.6±13.9% change). The BMI of the comparison group increased from baseline to the FABS-5+ visit (+10.3±20.6%). When the surgical group was split into maintainers and re-gainers, no differences in weight-related and eating behaviors, health responsibility, physical activity/inactivity, or dietary habits were observed between groups. However, at FABS-5+, maintainers had greater overall QOL scores than re-gainers (87.5±10.5 vs 65.4±20.2, P<0.001) and in each QOL sub-domain (P<0.01 all). CONCLUSIONS: Long-term weight outcomes for those who underwent weight-loss surgery were superior to those who did not undergo surgical treatment. While no behavioral factors were identified as predictors of success in long-term weight-loss maintenance, greater QOL was strongly associated with maintenance of weight loss among adolescents who underwent Roux-en-Y gastric bypass surgery surgery.

Evolution of larval competitiveness and associated life-history traits in response to host shifts in a seed beetle.

Resource competition is frequently strong among parasites that feed within small discrete resource patches, such as seeds or fruits. The properties of a host can influence the behavioural, morphological and life-history traits of associated parasites, including traits that mediate competition within the host. For seed parasites, host size may be an especially important determinant of competitive ability. Using the seed beetle, Callosobruchus maculatus, we performed replicated, reciprocal host shifts to examine the role of seed size in determining larval competitiveness and associated traits. Populations ancestrally associated with either a small host (mung bean) or a large one (cowpea) were switched to each other's host for 36 generations. Compared to control lines (those remaining on the ancestral host), lines switched from the small host to the large host evolved greater tolerance of co-occurring larvae within seeds (indicated by an increase in the frequency of small seeds yielding two adults), smaller egg size and higher fecundity. Each change occurred in the direction predicted by the traits of populations already adapted to cowpea. However, we did not observe the expected decline in adult mass following the shift to the larger host. Moreover, lines switched from the large host (cowpea) to the small host (mung bean) did not evolve the predicted increase in larval competitiveness or egg size, but did exhibit the predicted increase in body mass. Our results thus provide mixed support for the hypothesis that host size determines the evolution of competition-related traits of seed beetles. Evolutionary responses to the two host shifts were consistent among replicate lines, but the evolution of larval competition was asymmetric, with larval competitiveness evolving as predicted in one direction of host shift, but not the reverse. Nevertheless, our results indicate that switching hosts is sufficient to produce repeatable and rapid changes in the competition strategy and fitness-related traits of insect populations.

Effect of phentermine on weight reduction in a pediatric weight management clinic.

Phentermine is the most widely prescribed obesity medication in adults, yet studies of its use in the pediatric population are limited. We conducted a retrospective chart review of adolescents with obesity treated in a pediatric weight management clinic to examine the weight loss effectiveness of phentermine added to standard of care (SOC) lifestyle modification therapy versus SOC alone. All patients receiving phentermine plus SOC (n=25) were matched with a comparison group receiving only SOC (n=274). Differences at 1, 3 and 6 months were evaluated using generalized estimated equations adjusting for age, sex and baseline body mass index (BMI) and robust variance standard error estimates for confidence intervals and P-values. Phentermine use was associated with a greater percent change in BMI at 1 month (-1.6%; 95% confidence interval (CI): -2.6, -0.6%; P=0.001), 3 months (-2.9%; 95% CI: -4.5, -1.4%; P<0.001) and 6 months (-4.1%; 95% CI: -7.1, -1.0%; P=0.009) compared with SOC alone, with no differences in systolic or diastolic blood pressure between groups. Heart rate was higher at all time-points in the phentermine plus SOC compared with SOC-only group. These data suggest that short-term use of phentermine added to SOC may enhance weight loss in adolescents with obesity in the clinical setting.

Factors predicting incidence of post-operative delirium in older people following hip fracture surgery: a systematic review and meta-analysis.

OBJECTIVE: Delirium is one of the most common complications following hip fracture surgery in older people. This study identified pre- and peri-operative factors associated with the development of post-operative delirium following hip fracture surgery. METHODS: Published and unpublished literature were searched to identify all evidence reporting variables on patient characteristics, on-admission, intra-operative and post-operative management assessing incident delirium in older people following hip fracture surgery. Pooled odds ratio (OR) and mean difference of those who experienced delirium compared to those who did not were calculated for each variable. Evidence was assessed using the Downs and Black appraisal tool and interpreted using the GRADE approach. RESULTS: A total of 6704 people (2090 people with post-operative delirium) from 32 studies were analysed. There was moderate evidence of nearly a two-times greater probability of post-operative delirium for those aged 80 years and over (OR: 1.77; 95% CI: 1.09, 2.87), whether patients lived in a care institution pre-admission (OR: 2.65; 95% CI: 1.79, 3.92), and a six-times greater probability of developing post-operative delirium with a pre-admission diagnosis of dementia (OR: 6.07, 95% CI: 4.84, 7.62). There was no association with intra-operative variables and probability of delirium. CONCLUSION: Clinicians treating people with a hip fracture should be vigilant towards post-operative delirium if their patients are older, have pre-existing cognitive impairment and poorer overall general health. This is also the case for those who experience post-operative complications such as pneumonia or a urinary tract infection. Copyright © 2017 John Wiley & Sons, Ltd.

Unsupervised delineation of stratum corneum using reflectance confocal microscopy and spectral clustering.

BACKGROUND: Measuring the thickness of the stratum corneum (SC) in vivo is often required in pharmacological, dermatological, and cosmetological studies. Reflectance confocal microscopy (RCM) offers a non-invasive imaging-based approach. However, RCM-based measurements currently rely on purely visual analysis of images, which is time-consuming and suffers from inter-user subjectivity. METHODS: We developed an unsupervised segmentation algorithm that can automatically delineate the SC layer in stacks of RCM images of human skin. We represent the unique textural appearance of SC layer using complex wavelet transform and distinguish it from deeper granular layers of skin using spectral clustering. Moreover, through localized processing in a matrix of small areas (called 'tiles'), we obtain lateral variation of SC thickness over the entire field of view. RESULTS: On a set of 15 RCM stacks of normal human skin, our method estimated SC thickness with a mean error of 5.4 ± 5.1 µm compared to the 'ground truth' segmentation obtained from a clinical expert. CONCLUSION: Our algorithm provides a non-invasive RCM imaging-based solution which is automated, rapid, objective, and repeatable.

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle.

The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week-1 ) or ORX + trenbolone (TREN; 1.0 mg week-1 ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.

The Social, Historical, and Institutional Contingencies of Dam Removal.

Environmental managers in the United States and elsewhere are increasingly perceiving dam removal as a critical tool for river restoration and enhancing watershed resilience. In New England, over 125 dams have been dismantled for ecological and economic rationales. A surprising number of these removals, including many that are ongoing, have generated heated conflicts between restoration proponents and local communities who value their dammed landscapes. Using a comparative case study approach, we examine the environmental conflict around efforts to remove six dams in New England. Each of these removal efforts followed quite different paths and resultant outcomes: successful removal, stalled removal, and failure despite seemingly favorable institutional conditions. Lengthy conflicts often transpired in instances where removals occurred, but these were successfully arbitrated by paying attention to local historical-geographical conditions conducive to removal and by brokering effective compromises between dam owners and the various local actors and stakeholders involved in the removal process. Yet our results across all cases suggest that these are necessary, but not sufficient conditions for restoration through dam removal since a similar set of conditions typified cases where removals are continuously stalled or completely halted. Scholars examining the intersection between ecological restoration and environmental politics should remain vigilant in seeking patterns and generalities across cases of environmental conflict in order to promote important biophysical goals, but must also remain open to the ways in which those goals are thwarted and shaped by conflicts that are deeply contingent on historical-geographical conditions and broader institutional networks of power and influence.

Pediatric obesity pharmacotherapy: current state of the field, review of the literature and clinical trial considerations.

Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity.

Foraging mode affects the evolution of egg size in generalist predators embedded in complex food webs.

Ecological networks incorporate myriad biotic interactions that determine the selection pressures experienced by the embedded populations. We argue that within food webs, the negative scaling of abundance with body mass and foraging theory predict that the selective advantages of larger egg size should be smaller for sit-and-wait than active-hunting generalist predators, leading to the evolution of a difference in egg size between them. Because body mass usually scales negatively with predator abundance and constrains predation rate, slightly increasing egg mass should simultaneously allow offspring to feed on more prey and escape from more predators. However, the benefits of larger offspring would be relatively smaller for sit-and-wait predators because (i) due to their lower mobility, encounters with other predators are less common, and (ii) they usually employ a set of alternative hunting strategies that help to subdue relatively larger prey. On the other hand, for active predators, which need to confront prey as they find them, body-size differences may be more important in subduing prey. This difference in benefits should lead to the evolution of larger egg sizes in active-hunting relative to sit-and-wait predators. This prediction was confirmed by a phylogenetically controlled analysis of 268 spider species, supporting the view that the structure of ecological networks may serve to predict relevant selective pressures acting on key life history traits.