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Abstract Background Outcomes from studies employing nitisinone 10 mg and 2 mg in alkaptonuria were compared. Patients and methods Sixty‐nine patients in each of the nitisinone (10 mg daily) and controls of suitability of nitisinone in alkaptonuria 2 (SONIA 2), as well as 37 and 23 in nitisinone (2 mg daily) and control cohorts at the National Alkaptonuria Centre (NAC), respectively, were followed up for 4 years. Severity of alkaptonuria (AKU) was assessed by the AKU Severity Score Index (AKUSSI). 24‐h urine homogentisic acid (uHGA24), serum HGA (sHGA), serum tyrosine (sTYR) and serum nitisinone (sNIT) were also analysed at each time point. Dietetic support was used in the NAC, but not in SONIA 2. Safety outcomes were also compared. All statistical analyses were post hoc. Results The slope of the AKUSSI was 0.55, 0.19, 0.30, and 0.06 per month in the control NAC, nitisinone NAC, control SONIA 2, and nitisinone SONIA 2 cohorts, respectively. The intersection of the slopes on the x‐axis was −132, −411, −295, and − 1460 months, respectively. The control and nitisinone slope comparisons were statistically significant both in the NAC (p

Abstract Background Gender and biological sex are social and structural determinants of health and umbrella concepts encompassing many distinct attributes. This systematic review summarizes measures of gender and biological sex published in the biomedical literature. The goal was to identify measures that may be useful to researchers studying Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). Methods A search of PubMed, Embase, and PsycINFO (ProQuest platform) databases from 2000 to 2021 identified 1454 articles, which were then screened by five independent reviewers. Measures of gender and biological sex are summarized according to theoretical commitments and psychometric properties. Results Twenty‐nine measures were identified that assessed gender‐related constructs, and 4 were identified that assessed biological factors. Self‐report instruments characterized aspects of gender, such as gender stereotypes, norms, and ideologies. One measure was developed with a focus on older adults (65+ years). Discussion We offer recommendations to guide measurement of gender in AD/ADRD research, including how the use of specific existing measures may help advance AD/ADRD research. The lack of gender measures for older adults limits AD/ADRD research. New measures may be needed to address lifespan and generational differences in gender factors. Highlights A review of articles identifies 29 measures of gender in biomedical research. Gender is captured using multidimensional, self‐reported concepts. One measure was developed with a focus on older adults (65+).

Background and Aims. Regulatory pathways compare biosimilars with originator molecules only and not with other biosimilars. With the development of multiple infliximab biosimilars, patients may be asked to transition between them. Data is emerging but there is still a gap in the evidence on switching between infliximab biosimilars. Our aim was to conduct a full evaluation of switching a cohort of IBD patients from one biosimilar (CT-P13) to another (SB2) in a real-world setting including clinical and patient experience and molecular and drug immunogenicity aspects of the process. Methods. Prospective, phase IV interventional study of patients on CT-P13 switched to SB2. Demographics, disease history, validated disease activity scores, PROMs, and laboratory measurements were collected. Semistructured qualitative interviews were also conducted. Results. 133 out of 158 patients agreed to participate. Mean disease duration was 9.2 years. There was no difference in mean haemoglobin, platelet count, albumin, and C-reactive protein before and after switching. Mean faecal calprotectin at baseline and at week 30/32 was 306 μg/g versus 210 μg/g. Mean pMCS and mHBI at baseline were 1.54 and 3.14 versus 1.18 and 2.91 at week 30/32, respectively. Thirty-five subjects discontinued. There were 16 serious adverse events. Thematic analysis identified six major themes that reflected the patient experience—trust, clinical status at the point of switching, past experience, general disposition, information provision, and concerns/anxiety. Conclusions. Switching from CT-P13 to SB2 is safe and effective. Certain factors must be considered in supporting patient decision-making. These results support the development of clear, streamlined, and well-monitored biosimilar switching programmes.

Abstract Social monogamy has evolved multiple times and is particularly common in birds. However, it is not well understood why some species live in long‐lasting monogamous partnerships while others change mates between breeding attempts. Here, we investigate mate fidelity in a sequential polygamous shorebird, the snowy plover (Charadrius nivosus), a species in which both males and females may have several breeding attempts within a breeding season with the same or different mates. Using 6 years of data from a well‐monitored population in Bahía de Ceuta, Mexico, we investigated predictors and fitness implications of mate fidelity both within and between years. We show that in order to maximize reproductive success within a season, individuals divorce after successful nesting and re‐mate with the same partner after nest failure. Therefore, divorced plovers, counterintuitively, achieve higher reproductive success than individuals that retain their mate. We also show that different mating decisions between sexes predict different breeding dispersal patterns. Taken together, our findings imply that divorce is an adaptive strategy to improve reproductive success in a stochastic environment. Understanding mate fidelity is important for the evolution of monogamy and polygamy, and these mating behaviors have implications for reproductive success and population productivity.

After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.