Sex differences in exercise-induced diaphragmatic fatigue in endurance-trained athletes

There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 ± 1.9 ml·kg–1·min–1) and women (n = 19; maximal aerobic capacity = 57.1 ± 1.5 ml·kg–1·min–1). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a 15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 ± 2.3, 20.7 ± 3.2, and 13.3 ± 4.5%, respectively, whereas results in women (n = 8) were 21.0 ± 2.1, 11.6 ± 2.9, and 9.7 ± 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation

Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients

Purpose Lymphoma patients commonly experience declines in physical functioning and quality of life (QoL) that may be reversed with exercise training. Patients and Methods We conducted a randomized controlled trial in Edmonton, Alberta, Canada, between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and randomly assigned them to usual care (UC; n 62) or 12 weeks of supervised aerobic exercise training (AET; n 60). Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia. Secondary end points were overall QoL, psychosocial functioning, cardiovascular fitness, and body composition. Results Follow-up assessment for our primary end point was 96% (117 of 122) at postintervention and 90% (110 of 122) at 6-month follow-up. Median adherence to the supervised exercise program was 92%. At postintervention, AET was superior to UC for patient-rated physical functioning (mean group difference, 9.0; 95% CI, 2.0 to 16.0; P .012), overall QoL (P .021), fatigue (P .013), happiness (P .004), depression (P .005), general health (P .001), cardiovascular fitness (P .001), and lean body mass (P .008). Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning. AET did not interfere with chemotherapy completion rate or treatment response. At 6-month follow-up, AET was still borderline or significantly superior to UC for overall QoL (P .054), happiness (P .034), and depression (P .009) without an increased risk of disease recurrence/progression. Conclusion AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response. Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: a prespecified subgroup analysis of high-risk patients from the ECHELON-1 study

Approximately one‐third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high‐risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON‐1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first‐line therapy after a median follow‐up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD‐treated versus ABVD‐treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high‐risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON‐1 shows a favorable benefit‐risk balance in high‐risk patients

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity

The Use of a Compression Device as an Alternative to Hand-Sewn and Stapled Colorectal Anastomoses: Is Three a Crowd?

BackgroundThe NiTi CAR™ 27 is a newer device that uses compression to create an anastomosis. An analysis of this device in the creation of colorectal anastomoses in humans has yet to be reported in the USA.MethodsA non-randomized, prospective pilot study of the NiTi CAR™ 27 device in patients undergoing a left-sided colectomy between March 2008 and August 2009 was performed.ResultsTwenty-three patients (9 men and 14 women) underwent a left-sided colectomy and compression anastomosis with the CAR™ 27 device. Minor morbidities, 3 of 23 (13%) patients, included one small postoperative abscess requiring antibiotics alone and two postoperative anastomotic strictures requiring balloon dilation. Major morbidities, 1 of 23 (4%) patients, included a partial anastomotic dehiscence/leak requiring surgical dismantling of the anastomosis and diversion.ConclusionThe CAR™ 27 device shows promise as a safe and effective alternative for the creation of colorectal anastomoses. However, studies in a larger patient population are warranted to demonstrate equivalence of this device

Interactions between marine megafauna and plastic pollution in Southeast Asia

Southeast (SE) Asia is a highly biodiverse region, yet it is also estimated to cumulatively contribute a third of the total global marine plastic pollution. This threat is known to have adverse impacts on marine megafauna, however, understanding of its impacts has recently been highlighted as a priority for research in the region. To address this knowledge gap, a structured literature review was conducted for species of cartilaginous fishes, marine mammals, marine reptiles, and seabirds present in SE Asia, collating cases on a global scale to allow for comparison, coupled with a regional expert elicitation to gather additional published and grey literature cases which would have been omitted during the structured literature review. Of the 380 marine megafauna species present in SE Asia, but also studied elsewhere, we found that 9.1 % and 4.5 % of all publications documenting plastic entanglement (n = 55) and ingestion (n = 291) were conducted in SE Asian countries. At the species level, published cases of entanglement from SE Asian countries were available for 10 % or less of species within each taxonomic group. Additionally, published ingestion cases were available primarily for marine mammals and were lacking entirely for seabirds in the region. The regional expert elicitation led to entanglement and ingestion cases from SE Asian countries being documented in 10 and 15 additional species respectively, highlighting the utility of a broader approach to data synthesis. While the scale of the plastic pollution in SE Asia is of particular concern for marine ecosystems, knowledge of its interactions and impacts on marine megafauna lags behind other areas of the world, even after the inclusion of a regional expert elicitation. Additional funding to help collate baseline data are critically needed to inform policy and solutions towards limiting the interactions of marine megafauna and plastic pollution in SE Asia

Targeting vaccinations for the licensed dengue vaccine: considerations for serosurvey design

Background The CYD-TDV vaccine was unusual in that the recommended target population for vaccination was originally defined not only by age, but also by transmission setting as defined by seroprevalence. WHO originally recommended countries consider vaccination against dengue with CYD-TDV vaccine in geographic settings only where prior infection with any dengue serotype, as measured by seroprevalence, was >170% in the target age group. Vaccine was not recommended in settings where seroprevalence was <50%. Test-and-vaccinate strategies suggested following new analysis by Sanofi will still require age-stratified seroprevalence surveys to optimise age-group targeting. Here we address considerations for serosurvey design in the context of vaccination program planning. Methods To explore how the design of seroprevalence surveys affects estimates of transmission intensity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model for different combinations of age-range, survey size, transmission setting, and test sensitivity/specificity. We then used a Metropolis-Hastings Markov Chain Monte-Carlo algorithm to estimate the force of infection from each simulated dataset. Results Sampling from a wide age-range led to more accurate estimates than merely increasing sample size in a narrow age-range. This finding was consistent across all transmission settings. The optimum test sensitivity and specificity given an imperfect test differed by setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings. Conclusions When assessing vaccination suitability by seroprevalence surveys, countries should ensure an appropriate age-range is sampled, considering epidemiological evidence about the local burden of disease

Erratum: “Searches for Gravitational Waves from Known Pulsars at Two Harmonics in 2015–2017 LIGO Data” (2019, ApJ, 879, 10)

Due to an error at the publisher, in the published article the number of pulsars presented in the paper is incorrect in multiple places throughout the text. Specifically, "222" pulsars should be "221." Additionally, the number of pulsars for which we have EM observations that fully overlap with O1 and O2 changes from "168" to "167." Elsewhere, in the machine-readable table of Table 1 and in Table 2, the row corresponding to pulsar J0952-0607 should be excised as well. Finally, in the caption for Table 2 the number of pulsars changes from "188" to "187.

GW190412: Observation of a Binary-Black-Hole Coalescence with Asymmetric Masses

We report the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO’s and Virgo’s third observing run. The signal was recorded on April 12, 2019 at 05∶30∶44 UTC with a network signal-to-noise ratio of 19. The binary is different from observations during the first two observing runs most notably due to its asymmetric masses: a ∼30 M_⊙ black hole merged with a ∼8 M_⊙ black hole companion. The more massive black hole rotated with a dimensionless spin magnitude between 0.22 and 0.60 (90% probability). Asymmetric systems are predicted to emit gravitational waves with stronger contributions from higher multipoles, and indeed we find strong evidence for gravitational radiation beyond the leading quadrupolar order in the observed signal. A suite of tests performed on GW190412 indicates consistency with Einstein’s general theory of relativity. While the mass ratio of this system differs from all previous detections, we show that it is consistent with the population model of stellar binary black holes inferred from the first two observing runs