The surprising complexity and diversity of sperm storage structures across Galliformes

In internal fertilisers, the precise timing of ovulation with the arrival of sperm at the site of fertilisation is essential for fertilisation success. In birds, mating is often not synchronised with ovulation, but instead females utilise specialised sperm storage tubules (SSTs) in the reproductive tract, which can ensure sperm are always available for fertilisation at the time of ovulation, whilst simultaneously providing a mechanism of post‐copulatory sexual selection. Despite the clear importance of SSTs for fertilisation success, we know little about the mechanisms involved in sperm acceptance, storage, and release. Furthermore, most research has been conducted on only a small number of species, based on which SSTs are usually assumed to look and function in the same way across all species. Here, we conduct a comparative exploration of SST morphology across 26 species of Galliformes. We show that SSTs, and the surrounding tissue, can vary significantly in morphology across species. We provide observational evidence that Galliformes exhibit at least 5 distinct categories of tubule types, including distinctive coiled and multi‐branched tubules, and describe 2 additional features of the surrounding tissue. We suggest functional explanations for variation in tubule morphology and propose next steps for future research. Our findings indicate that SSTs are likely to be far more variable than has previously been assumed, with potentially important consequences for our understanding of sperm storage in birds and post‐copulatory sexual selection in general

A sex-linked supergene with large effects on sperm traits has little impact on reproductive traits in female zebra finches.

Despite constituting an essential component of fitness, reproductive success can vary remarkably between individuals and the causes of such variation are not well understood across taxa. In the zebra finch—a model songbird, almost all the variation in sperm morphology and swimming speed is maintained by a large polymorphic inversion (commonly known as a supergene) on the Z chromosome. The relationship between this polymorphism and reproductive success is not fully understood, particularly for females. Here, we explore the effects of female haplotype, and the combination of male and female genotype, on several primary reproductive traits in a captive population of zebra finches. Despite the inversion polymorphism's known effects on sperm traits, we find no evidence that inversion haplotype influences egg production by females or survival of embryos through to hatching. However, our findings do reinforce existing evidence that the inversion polymorphism is maintained by a heterozygote advantage for male fitness. This work provides an important step in understanding the causes of variation in reproductive success in this model species

Physiological factors influencing female fertility in birds

Fertility is fundamental to reproductive success, but not all copulation attempts result in a fertilized embryo. Fertilization failure is especially costly for females, but we still lack a clear understanding of the causes of variation in female fertility across taxa. Birds make a useful model system for fertility research, partly because their large eggs are easily studied outside of the female's body, but also because of the wealth of data available on the reproductive productivity of commercial birds. Here, we review the factors contributing to female infertility in birds, providing evidence that female fertility traits are understudied relative to male fertility traits, and that avian fertility research has been dominated by studies focused on Galliformes and captive (relative to wild) populations. We then discuss the key stages of the female reproductive cycle where fertility may be compromised, and make recommendations for future research. We particularly emphasize that studies must differentiate between infertility and embryo mortality as causes of hatching failure, and that non-breeding individuals should be monitored more routinely where possible. This review lays the groundwork for developing a clearer understanding of the causes of female infertility, with important consequences for multiple fields including reproductive science, conservation and commercial breeding

Why do eggs fail? Causes of hatching failure in threatened populations and consequences for conservation

Reproductive failure is ubiquitous. However, research on the mechanisms underpinning reproductive failure is still lacking in most species. This gap in our understanding has particularly strong repercussions for threatened species and it hinders our ability to establish effective interventions to improve survival. In this review, we focus on why eggs fail to hatch – one of the most critical and understudied aspects of bird reproduction. We identify the main drivers of hatching failure in threatened populations of birds and the key mechanisms that cause failure at different stages of development inside the egg. We then discuss the importance of management interventions aimed at reducing hatching failure in species of conservation concern. Our review highlights the need for a better understanding of the mechanistic basis of hatching failure in non‐model bird species and identifies the methodological tools necessary to achieve this

Mortality within 30 days of chemotherapy: a clinical governance benchmarking issue for oncology patients

No national benchmark figures exist for early mortality due to chemotherapy unlike for surgical interventions. Deaths within 30 days of chemotherapy during a 6-month period were identified from the Royal Marsden Hospital electronic patient records. Treatment intention – curative or palliative, cause of death and number of previous treatments – were documented. Between April 2005 and September 2005, 1976 patients received chemotherapy with 161 deaths within 30 days of chemotherapy (8.1%). Of these, 124 deaths (77.0%) were due to disease progression. Of the other 37 deaths, 12 (7.5%) were related to chemotherapy, six each for solid tumours and haematological malignancies, of which seven (4.3%) were due to neutropenic sepsis. For the remaining 25 deaths (15.5%) there was insufficient information. There were more deaths after third and subsequent lines of therapy than with first and secondlines of therapy. Only 12 of the 161 deaths occurred in patients who were receiving potentially curative chemotherapy to give a mortality rate in breast and gastrointestinal malignancy of 0.5 and 1.5%, respectively. It is possible to audit mortality within 30 days of chemotherapy and this should become a benchmark for standard practice nationally. Most deaths were due to disease progression in the palliative setting. We practice this form of audit each quarter and feed back to the treating teams so that deaths are discussed and practice monitored

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2–3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second- or third-line therapy. The initial dose of S-1 was 35 mg m−2, administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progression-free survival, and overall survival were 11 weeks (95% CI, 8–14) and 33 weeks (95% CI, 19–47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3–21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32–60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status

Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m−2 day−1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m−2 day−1, stepping up to 100 mg m−2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m−2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m−2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m−2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1–13). The incidences of severe (grade 3–4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2–76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity