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Context Home-range size and population density characteristics are crucial information in the design of effective wildlife management, whether for conservation or control, but can vary widely among populations of the same species. Aims We investigate the influence of site productivity on home-range size and population density for Australian populations of the native, threatened spotted-tailed quoll (Dasyurus maculatus) and the alien and highly successful feral cat (Felis catus). Methods We use live trapping and fine-scale GPS tracking to determine the home-range size and population density for both species across five sites in Tasmania. Using these data, as well as published estimates for both species from across Australia, we model how these parameters change in response to productivity gradients. We also use the telemetry data to examine the energetic costs of increasing home-range size for both species. Key results For both species, decreasing site productivity correlates with lower population density, and in spotted-tailed quolls and female feral cats, it also correlates with larger home-range sizes. However, the relative magnitude of these changes is different. Feral cats show smaller increases in home-range size but larger decreases in population density relative to spotted-tailed quolls. Our results suggest that these differences may be because increases in home-range size are more costly for feral cats, demonstrated by larger increases in nightly movement for the same increase in home-range area. Conclusions We suggest that knowledge of both home-range size and population density is needed to accurately determine how species respond to habitat productivity, and inform effective management across their geographic range. Implications These results have clear management implications; for example, in our low-rainfall sites, an adult female spotted-tailed quoll requires up to five times the amount of habitat expected on the basis of previous studies, thus dramatically increasing the costs of conservation programs for this threatened native species. Conversely, productivity-driven differences of up to four-fold in feral cat population density would influence the resources required for successful control programs of this invasive species.

In earlier physiologically based pharmacokinetic (PBPK) models for manganese (Mn), the kinetics of transport of Mn into and out of tissues were primarily driven by slow rates of association and dissociation of Mn with tissue binding sites. However, Mn is known to show rapidly reversible binding in tissues. An updated Mn model for primates, following similar work with rats, was developed that included rapid association/dissociation processes with tissue Mn-binding sites, accumulation of free Mn in tissues after saturation of these Mn-binding sites and rapid rates of entry into tissues. This alternative structure successfully described Mn kinetics in tissues in monkeys exposed to Mn via various routes including oral, inhalation, and intraperitoneal, subcutaneous, or intravenous injection and whole-body kinetics and tissue levels in humans. An important contribution of this effort is showing that the extension of the rate constants for binding and cellular uptake established in the monkey were also able to describe kinetic data from humans. With a consistent model structure for monkeys and humans, there is less need to rely on cadaver data and whole-body tracer studies alone to calibrate a human model. The increased biological relevance of the Mn model structure and parameters provides greater confidence in applying the Mn PBPK models to risk assessment. This model is also well-suited to explicitly incorporate emerging information on the role of transporters in tissue disposition, intestinal uptake, and hepatobiliary excretion of Mn.

Background Chondrosarcomas are rare, malignant chondroid tumors that can occur in the sinonasal and skull base regions. Surgery is a mainstay of treatment, but complete resection can be challenging because of the close proximity of critical neurovascular structures. Because of their rarity and relatively indolent nature, optimal treatment regimens are not established. Our objective was to assess determinants of survival for sinonasal and skull base chondrosarcomas utilizing the National Cancer Database (NCDB). Methods The NCDB (2004-2017) was queried for cases of sinonasal and skull base chondrosarcoma. Multivariate hazard regression modeling was used to identify significant predictors of 60-month and 120-month overall survival (OS). Results Seven hundred thirty-six cases met inclusion criteria. OS for all treatment types was 84.7% [SE±0.02] at 60 months and 75.6% [SE±0.02] at 120 months. Surgery with or without adjuvant treatment was found to associate with highest OS at 60 and 120 months. For patients receiving adjuvant radiation during treatment, proton therapy had significantly better OS at 60 months (95.4% [SE±0.03] vs 82.3% [SE±0.03], -2 = 5.27; p = 0.02) and 120 months (85.1% [SE±0.08] vs 72.8% [SE±0.05], -2 = 4.11; p = 0.04) compared with conventional external beam. After adjustment for primary site, multivariate Cox regression modeling (n = 561) identified cofactors significantly associated with variation in mortality risk at 60 and 120 months, including age, Charlson-Deyo total score ≥ 3, insurance provision status, and tumor grade. Conclusions Sinonasal and skull base chondrosarcoma are primarily treated with surgery with favorable OS. Adjuvant treatment may be required and proton radiation was associated with improved 60-month and 120-month survival compared with conventional radiation.

This article presents the investigation of circuit modelling, design, and optimization of the class-E rectifier to achieve a near-resistive impedance during a large load-range. Based on circuit modelling and impedance depiction, a circuit design concept of impedance compensation to achieve near-resistive impedance is proposed, and we selected the series inductor as the compensation network for class-E rectifiers. After an optimized design, a 6.78-MHz wireless power transfer prototype was built with applying the proposed concept and tested. The experimental results match well with the circuit modelling and validate the impedance shift can be optimized by the proposed circuit design concept. The experimental prototype achieves 87.2% dc–dc efficiency at the rated 220-W output and the phase angle shift is lower than 10 $^ \circ$ during the load decreasing from 220-W rated output to the 40-W light-load output. We also discuss the circuit design considerations and the hardware implementation of the prototype for the proposed design concept.

This paper presents an analysis of the different loss modes of the switching devices in a class-D series resonant converter operating with either a fixed dead time or fixed duty cycle. A feasible operating region where the FETs in the inverter stage only exhibit reverse conduction losses, with no hard switching, is identified. Furthermore, the impact of using a fixed dead time compared to a fixed duty cycle is investigated. We find that using a fixed dead time is superior to using a fixed duty cycle, as a broader operating range can be achieved for the same losses, or the same operating range can be achieved with lower losses. A reduction in the reverse conduction losses of up to 59% or an expansion of the operational frequency range by 33% when using a fixed dead time is found. The modeling approach is validated on a 1-MHz prototype employing GaN switching devices. Lastly, a design example shows how the presented analysis can be used to determine the optimal fixed dead time/duty cycle for use with frequency modulation control such that the losses are minimized.

This article presents the analytical modeling of synchronous class E rectifiers with the load-independent operation, which achieves zero-phase-angle input impedance, soft-switching over the entire load range with a constant voltage gain. The optimal design of the synchronous class E rectifier is proposed to realize both zero-voltage-switching turn- on and zero-current-switching turn- off at the expected output power. An $ LCC$ - $S$ compensated MHz-WPT topology, which comprises the push–pull class E inverter and rectifier with the load-independent operation, is proposed to achieve the fully soft-switching and a nearly constant voltage gain over the entire load range. The efficiency improvement of the compensation network is also investigated to provide a design methodology for the proposed topology. A $ 6.78$ -MHz WPT prototype, along with an alternative phase detector using an auxiliary coil to realize phase detection, is built to validate the analytical model and the proposed methodology. The system efficiency reaches $ \text{86.7}\%$ at $ 214$ -W output. The synchronous push–pull class E rectifier maintains soft-switching over the load range, and the rectification efficiency reaches $ 94.6\%$ .

Purpose: TP53 aberration (TP53 mutation and/or 17p deletion) is the most important predictive marker in chronic lymphocytic leukemia (CLL). Although each TP53 aberration is considered an equal prognosticator, the prognostic value of carrying isolated (single-hit) or multiple (multi-hit) TP53 aberrations remains unclear, particularly in the context of targeted agents. Patients and Methods: We performed deep sequencing of TP53 using baseline samples collected from 51 TP53 aberrant patients treated with ibrutinib in a phase II study (NCT01500733). Results: We identified TP53 mutations in 43 patients (84%) and del(17p) in 47 (92%); 9 and 42 patients carried single-hit and multi-hit TP53, respectively. The multi-hit TP53 subgroup was enriched with younger patients who had prior treatments and unmutated immunoglobulin heavy-chain variable region gene status. We observed significantly shorter overall survival, progression-free survival (PFS), and time-to-progression (TTP) in patients with multi-hit TP53 compared with those with single-hit TP53. Clinical outcomes were similar in patient subgroups stratified by 2 or >2 TP53 aberrations. In multivariable analyses, multi-hit TP53 CLL was independently associated with inferior PFS and TTP. In sensitivity analyses, excluding mutations below 1% VAF demonstrated similar outcome. Results were validated in an independent population-based cohort of 112 patients with CLL treated with ibrutinib. Conclusions: In this study, single-hit TP53 defines a distinct subgroup of patients with an excellent long-term response to single-agent ibrutinib, whereas multi-hit TP53 is independently associated with shorter PFS. These results warrant further investigations on prognostication and management of multi-hit TP53 CLL. See related commentary by Bomben et al., p. 4462

This study carries out a cross-country analysis of changes in quantity and quality of life during the first year of the COVID-19 pandemic for 124 countries. Changes in the quantity of life are measured as life years lost to COVID-19, including excess deaths not officially reported as COVID-19 deaths. Changes in quality of life are proxied by the average change in daily mobility, compared to a pre-COVID baseline. We find a significant negative correlation between the two, meaning that the countries with the biggest reductions in mobility are also the countries with the biggest losses of life years. We calculate that about 48 million life years were lost during the first year of the pandemic, corresponding to 0.018% of all expected life years. For comparison, at least double the amount of life years are lost every year due to children dying of diarrhea. About 28 million life years are created every day from babies being born, so the first year of the pandemic set us back less than two days in terms of quantity of life. The setbacks in terms of quality of life are several orders of magnitude larger. Some countries have suffered close to a 50% reduction in mobility sustained over 12 months, with devastating effects on many aspects of quality of life. We estimate that 1.2 billion quality life years were lost due to mobility reductions, which is 25 times as many as life years lost due to COVID-19 related deaths during the first year of the pandemic.

We report a simple method for copper-catalyzed benzylic C–H alkynylation that uses alkynylboronic esters as nucleophilic coupling partners. The catalytic system is readily available and the reaction takes place under mild conditions. Different substrates for the C–H functionalization, as well as various alkynylboronic ester nucleophiles, were evaluated. Finally, three examples of enantioselective C–H alkynylations are presented.

Background: Manual semen assessment (MSA) is a key component in a male’s fertility assessment. Clinicians rely on it to make diagnostic and treatment decisions. When performed manually, this routine laboratory test is prone to variability due to human intervention which can lead to misdiagnosis and consequently over- or under-treatment. For standardization, continuous training, quality control (QC) programs and pricy Computer-Assisted Sperm Analysis (CASA) systems have been proposed, yet, without resolving intra- and inter-laboratory variability. In response, promising simplified sperm testing devices, able to provide cost-effective point-of-care male infertility diagnosis are prospected as a plausible solution to resolve variability and increase access to sperm testing. Materials and methods: A throughout literature research for semen testing, sperm analysis, smart-phone assisted semen analysis, ‘at-home’ semen testing, male infertility, infertility in developing countries, infertility in low- and middle-income countries (LMIC) and quantitative sperm analysis was performed. A total of 14 articles, specific to ‘at-home’ simplified sperm assessment, were included to treat the core subject. Results: Continuous training and consistent QC, are sine qua none conditions to achieve accurate and comparable MSA. Compliance does not rule-out variability, nevertheless. Emerging simplified sperm assessment devices are an actual alternative to resolve lack of standardization and accessibility to sperm analysis. YO®, SEEM®, and ExSeed® are commercially available, user-friendly smartphone-based devices which can accurately measure volume, sperm concentration (millions/ml) and total motile sperm count. More broadly, by cost-effectiveness, availability, accuracy and convenient application, these devices could effectively sort patients for first-line artificial reproduction treatments such as intrauterine insemination. Conclusions: Accuracy and cost-effectiveness make smart-phone based sperm testing devices a practical and realistic solution to overcome variability in MSA. Importantly, these tools represent an actual opportunity to standardize and affluence male subfertility diagnosis and treatment, especially in LMIC. However, before clinical application is possible, guidelines, further testing with special attention on accuracy in washed sperm, availability, cost-benefit and reliability are required.

Background Patient adherence to topical antipsoriatic drugs is often poor, leading to poor efficacy. Use of long-term support delivered by dermatological nurses to patients treated with topical drugs may improve outcome. Aim To evaluate whether regular support from dermatological nurses improves outcome and treatment adherence in patients with psoriasis receiving topical medications. Methods We conducted a randomized controlled trial (RCT) (clinicaltrials.gov registration NCT04220554), in which patients received once-daily topical medications (containing corticosteroids and/or calcipotriol) for as long as their psoriasis was visible. The patients were randomly allocated to standard care by the dermatologist either with (n = 51) or without (n = 52) support from dermatological nurses. The nurse support intervention consisted of a structured dermatological consultation at baseline and Week 1, followed by contact with a nurse each month (in the outpatient clinic or by telephone). The primary outcome was severity of psoriasis, which was measured by the Lattice System Physician's Global Assessment (LS-PGA) and assessed by intention-to-treat analyses using linear mixed regression models for longitudinal data. Secondary outcomes were quality of life (measured by the Dermatology Life Quality Index; DLQI) and good adherence (defined as use of ≥ 80% of recommended doses). Results In total, 92 patients (89%) completed the 48-week trial period. The intervention group improved more than the nonintervention group from baseline to Week 24 in LS-PGA (2.21 vs. 1.28, P = 0.001) and in DLQI at Week 12 (6.50 vs. 1.55, P < 0.001). Differences between the two groups in favour of the intervention were observed throughout the study period. More participants in the intervention group had good adherence compared with the nonintervention group (36% vs. 14%, P < 0.001). Conclusion Regular, continued patient support from dermatological nurses increased the efficacy of psoriasis treatment, improved quality of life and enhanced long-term adherence to topical antipsoriatic drugs. However, there is still room for more improvement.

This article investigates the modeling and implementation of the load-independent operation for the push–pull Class E topology with coupled inductors. The analytical modeling is first presented and provides a new design methodology, which distantly improves the soft-switching performance, load regulation, and efficiency compared with the conventional inductor-coupled Class E topology. An LCC-S resonant Class E$ ^2$ converter, which combines the load-independent inductor-coupled inverter and active rectifier, is proposed for MHz-wireless power transfer (MHz-WPT) applications. The active inductor-coupled Class E rectifier maintains soft switching, constant voltage gain, and zero-phase-angle input at various loads. A three-winding magnetic structure is also proposed to improve the coupled inductors by enhanced self-inductance, which features more effective harmonic suppression with lower magnetic losses and volumes. By the proposed methodology and the improved magnetic structure, the converter features negligible harmonic contents and maintains soft switching with a constant voltage conversion ratio over the entire load range. A 6.78-MHz WPT prototype was built to verify the proposed methodology with detailed parameter design and hardware implementation. The prototype realizes load-independent zero-voltage switching and maintains an approximately constant voltage gain with +5/$-$4% variance from no-load to 320-W output power. The measured dc–dc efficiency reaches 89.3% at 210 W.

Study question Does diet-induced weight loss improve semen parameters, and are these possible improvements maintained with sustained weight loss? Summary answer An 8-week low-calorie diet-induced weight loss was associated with improved sperm count, which was maintained after one year in men who maintained weight loss. What is known already Obesity is associated with impaired semen parameters. Weight loss improves metabolic health in obesity, but there is a lack of knowledge on the acute and long-term effects of weight loss on semen parameters. Study design, size, duration This is a substudy of men with obesity enrolled in a randomised, controlled, double-blinded trial (the S-LITE trial). The trial was conducted between August 2016 and November 2019. A total of 56 men was included in the study and assigned to an initial 8-week low-calorie diet (800 kcal/day) followed by randomisation to 52 weeks of either: placebo, exercise training, and placebo (exercise), the GLP-1 analogue liraglutide (liraglutide) or liraglutide in combination with exercise training (combination). Participants/materials, setting, methods Inclusion criteria were men who delivered semen samples, 18 to 65 years of age and a body mass index between 32 to 43 kg/m2, but otherwise healthy. The study was carried out at Hvidovre Hospital and at the University of Copenhagen, and the participants were from the Greater Copenhagen Area. We assessed semen parameters, anthropometrics and collected blood samples before (T0) and after the 8-week low-calorie dietary intervention (T1) and after 52 weeks (T2). Main results and the role of chance The men lost on average 16.5 kg (95% CI: 15.2-17.8) bodyweight during the low-calorie diet, which increased sperm concentration 1.49 fold (95% CI: 1.18-1.88, P Limitations, reasons for caution The S-LITE trial was a randomised controlled trial of weight loss maintenance. Analysis of semen was preregistered to explore the effects of weight loss and weight loss maintenance on semen parameters. Due to the small sample size, definite inferences cannot be made. Wider implications of the findings This study shows that sperm concentration and sperm count were improved after a diet-induced weight loss in men with obesity. Our findings indicate that both liraglutide and exercise as weight maintenance strategies may be used to maintain the improvements in sperm concentration and count. Trial registration number H-16027082

Study question How does computer-assisted semen analysis (CASA) (Lenshooke, LOGIXX) and at-home sperm testing (ExSeed) compare with manual methodology assessment of male fertility based on WHO criteria (5thEdition); a three-method comparison study. Summary answer All methods showed good agreement for concentration and limited agreement for motility highlighting the need for further development of alternatives to manual assessment. What is known already Several studies have shown good correlation between CASA systems and laboratory-based manual semen analysis, but only a few have carried out a three-way comparison study. One of which showed positive correlation with motility and concentration between a smartphone-based semen analysis and laboratory-based CASA system and positive correlation between concentration and motility between the smartphone-based CASA system and microscopic-based results. The at-home sperm test kit may play a role in motivating infertile males to visit clinics for early diagnosis and also reducing the need for multiple visits to the fertility clinic for repeat semen analyses. Study design, size, duration Fifty patients (between 29 and 56 years) attending a fertility clinic were included in the study between September 2021 to December 2021. Semen samples were split into 3 aliquots and evaluated using manual semen assessment (MSA) according to the WHO 5th Edition (2010) guidelines, the ExSeed Home Sperm Test (HST) and the LensHooke® X1 PRO Semen Quality Analyzer (CASA). Participants/materials, setting, methods The semen samples were collected from fifty participants at CARE Fertility Tunbridge Wells. The samples were placed in an incubator at 37°C for 30 minutes to liquefy. After liquefaction, sperm concentration, total motility, total motile sperm count (TMSC) and normal morphology were evaluated. Spearman’s Rank correlations (>0.7) and Chi-squared tests were used and the p-value < 0.05 was considered as statistically significant. Main results and the role of chance All variables were highly significantly (p < 0.0002) positively correlated between all 3 methods. The greatest correlations were obtained for sperm concentration (CASA/HST: r = 0.826; MSA/HST: r = 0.870; MSA/CASA: r = 0.871) and TMSC (MSA/CASA: p = 0.792; CASA/HST: r = 0.800; MSA/HST: r = 0.854). Correlations for motility were markedly lower (MSA/HST: r = 0.611; CASA/HST: r = 0.717; MSA/LCASA: r = 0.750). The lowest correlation was found for morphology (MSA/CASA: r = 0.500). The HST device does not determine morphology. As compared to MSA, using the HST device agreement for normal or low sperm concentration (≥15 × 106/mL or < 15 × 106/mL respectively) was identified in 84.3% of the cases, whereas 94.0% with CASA. The agreement between CASA and HST was 82.0%. For total motility ≥ or < 40%, the agreements were 68.0% (CASA/HST), 56.9% (MSA/HST) and 82.0% (MSA/CASA), respectively. For the identification of patients with normal morphology >4%, the agreement between MSA and CASA was 30%. Limitations, reasons for caution The small sample size was 50 cases. The home testing device does not assess morphology. Furthermore, it is difficult to ascertain whether a consumer would carry out the analysis with this device with the same accuracy as an embryologist. Wider implications of the findings The need for repeated semen analyses, the effect of the COVID-19 pandemic and the discomfort some patients feel in a clinical setting, necessitate the need for evaluation of novel semen analysis approaches. These emerging technologies have potential to be more patient friendly, convenient and efficient than standard semen assessment methods. Trial registration number not applicable

Studies using magnetoencephalography (MEG) have identified the orbitofrontal cortex (OFC) to be an important early hub for a “parental instinct” in the brain. This complements the finding from functional magnetic resonance imaging studies linking reward, emotion regulation, empathy, and mentalization networks to the “parental brain.” Here, we used MEG in 43 first-time mothers listening to infant and adult cry vocalizations to investigate the link with mother–infant postpartum bonding scores and their level of sleep deprivation (assessed using both actigraphy and sleep logs). When comparing brain responses to infant versus adult cry vocalizations, we found significant differences at around 800–1,000 ms after stimuli onset in the primary auditory cortex, superior temporal gyrus, hippocampal areas, insula, precuneus supramarginal gyrus, postcentral gyrus, and posterior cingulate gyrus. Importantly, mothers with weaker bonding scores showed decreased brain responses to infant cries in the auditory cortex, middle and superior temporal gyrus, OFC, hippocampal areas, supramarginal gyrus, and inferior frontal gyrus at around 100–300 ms after the stimulus onset. In contrast, we did not find correlations with sleep deprivation scores. The significant decreases in brain processing of an infant’s distress signals could potentially be a novel signature of weaker infant bonding in new mothers and should be investigated in vulnerable populations.