Bovine fertility remains a critical issue underpinning the sustainability of the agricultural sector. Phenotypic records collected on >7,000 bulls used in artificial insemination (AI) were used to ...identify 160 reliable and divergently fertile bulls for a dual strategy of targeted sequencing (TS) of fertility-related β-defensin genes and whole exome sequencing (WES). A haplotype spanning multiple β-defensin genes and containing 94 SNPs was significantly associated with fertility and functional analysis confirmed that sperm from bulls possessing the haplotype showed significantly enhanced binding to oviductal epithelium. WES of all exons in the genome in 24 bulls of high and low fertility identified 484 additional SNPs significantly associated with fertility. After validation, the most significantly associated SNP was located in the FOXJ3 gene, a transcription factor which regulates sperm function in mice. This study represents the first comprehensive characterisation of genetic variation in bovine β-defensin genes and functional analysis supports a role for β-defensins in regulating bull sperm function. This first application of WES in AI bulls with divergent fertility phenotypes has identified a novel role for the transcription factor FOXJ3 in the regulation of bull fertility. Validated genetic variants associated with bull fertility could prove useful for improving reproductive outcomes in cattle.
Purpose - The purpose of this paper is to determine head and neck cancer patients' perspective of their follow-up regime and to suggest ways in which these perspectives can be incorporated into ...current practice.Design methodology approach - This is a prospective survey-based study. A total of 263 patients consecutively attending a head and neck cancer clinic completed a survey about their experience of the follow-up process in the post-treatment period between January 2009 and October 2009.Findings - The paper finds that, of the patients, 67 per cent (n=176) felt that the clinic met the goals they hoped would be achieved during their visit; 84 per cent (n=221) felt that their follow-up visits were too frequent. In total 60 per cent (n=159) were booked to see both an allied health professional and the attending clinician. Of these, 84 per cent (n=134 159) felt that issues addressed at follow-up with the clinician duplicated those addressed by the allied healthcare professionals. When asked about their opinion of a less intensive follow-up system based on patients reporting problems and requesting appointments, 73 per cent (n=192) favoured it. When asked who they would like to contact first in such a system, most patients (n=118, 45 per cent) stated a clinical nurse specialist.Practical implications - Current follow-up regimes may be too prescriptive in their approach without taking patient perspective into consideration. Patients felt that being seen intensively for the first year, then having visits tapered off over the next two years and finally being seen according to symptoms thereafter to be appropriate and felt that this represented an overall better system.Originality value - These data suggest the need for a more patient-focused, individualised approach to follow-up in head and neck cancer.
Purpose Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane ...(TaxAC) is unknown. Methods In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis). Results A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC ( P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative. Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer compared with the TC6 regimen.
The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2021 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the management of blood pressure in ...chronic kidney disease (CKD). This commentary is the product of that work group and presents the recommendations and practice points from the KDIGO guideline in the context of US clinical practice. A critical addition to the KDIGO guideline is the recommendation for accurate assessment of blood pressure using standardized office blood pressure measurement. In the general adult population with CKD, KDIGO recommends a goal systolic blood pressure less than 120 mm Hg on the basis of results from the Systolic Blood Pressure Intervention Trial (SPRINT) and secondary analyses of the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. The KDOQI work group agreed with most of the recommendations while highlighting the weak evidence base especially for patients with diabetes and advanced CKD.
CrCoNi-based medium- and high-entropy alloys display outstanding damage tolerance, especially at cryogenic temperatures. In this study, we examined the fracture toughness values of the equiatomic ...CrCoNi and CrMnFeCoNi alloys at 20 kelvin (K). We found exceptionally high crack-initiation fracture toughnesses of 262 and 459 megapascal-meters
½
(MPa·m
½
) for CrMnFeCoNi and CrCoNi, respectively; CrCoNi displayed a crack-growth toughness exceeding 540 MPa·m
½
after 2.25 millimeters of stable cracking. Crack-tip deformation structures at 20 K are quite distinct from those at higher temperatures. They involve nucleation and restricted growth of stacking faults, fine nanotwins, and transformed epsilon martensite, with coherent interfaces that can promote both arrest and transmission of dislocations to generate strength and ductility. We believe that these alloys develop fracture resistance through a progressive synergy of deformation mechanisms, dislocation glide, stacking-fault formation, nanotwinning, and phase transformation, which act in concert to prolong strain hardening that simultaneously elevates strength and ductility, leading to exceptional toughness.
Too cold to fracture
Finding structural materials that have good fracture properties at very low temperatures is challenging but is important for fields such as space exploration. Liu
et al
. discovered a high-entropy chromium-cobalt-nickel alloy that has an incredibly high fracture toughness at 20 kelvin (see the Perspective by Zhang and Zhang). This behavior is caused by an unexpected phase transformation that, when combined with other microstructures, prevents crack formation and propagation. The fracture toughness of this alloy makes it potentially useful for a range of cryogenic applications. —BG
CrCoNi-based alloys have very high fracture toughness at 20 kelvin.
Acute-onset postoperative endophthalmitis after cataract surgery remains a rare but important cause of visual loss. There is no global consensus regarding the optimal strategies for prophylaxis of ...endophthalmitis and practices vary substantially around the world, especially with respect to the use of intracameral antibiotics. The European Society of Cataract & Refractive Surgeons in a randomized clinical trial (2007) reported an approximately 5-fold reduction in endophthalmitis rates associated with the use of intracameral cefuroxime. Despite this report, the use of intracameral antibiotics has not been universally adopted.
Various endophthalmitis prophylaxis patterns around the world (including the United States, Canada, Australia/New Zealand, Japan, China, India, Indonesia, South Africa, Argentina, Russia, Sweden and Mexico) are compared. Each contributing author was asked to provide similar information, including endophthalmitis rates based on published studies, current practice patterns, and in some cases original survey data. Various methods were used to obtain this information, including literature reviews, expert commentary, and some new survey data not previously published.
Many different practice patterns were reported from around the world, specifically with respect to the use of intracameral antibiotics.
There is no worldwide consensus regarding endophthalmitis prophylaxis with cataract surgery.
The mineralogy and mixing state of dust particles originating from the African continent influences climate and marine ecosystems in the North Atlantic due to its effect on radiation, cloud ...properties and biogeochemical cycling. However, these processes are difficult to constrain because of large temporal and spatial variability, and the lack of in situ measurements of dust properties at all stages of the dust cycle. This lack of measurements is in part due to the remoteness of potential source areas (PSAs) and transport pathways but also because of the lack of an efficient method to report the mineralogy and mixing state of single particles with a time resolution comparable to atmospheric processes, which may last a few hours or less. Measurements are equally challenging in laboratory simulations where dust particles need to be isolated and characterised in low numbers whilst conditions are dynamically controlled and monitored in real time. This is particularly important in controlled expansion cloud chambers (CECCs) where ice-nucleating properties of suspended dust samples are studied in cold and mixed phase cloud conditions.
Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR ...mutation, is found in 3-4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio OR = 6.4, 95% confidence interval CI 2.6-15.6, p = 4.2 × 10
), which was replicated in the Penn Medicine Biobank (OR = 1.6, 95% CI 1.2-2.4, p = 6.0 × 10
) and Million Veteran Program (OR = 1.5, 95% CI 1.2-1.8, p = 1.8 × 10
). Polyneuropathy prevalence among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. The cumulative incidence of common hATTR amyloidosis manifestations (carpal tunnel syndrome, polyneuropathy, cardiomyopathy, heart failure) was significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, 95% CI 1.7-4.5, p = 2.6 × 10
) in the UK Biobank, with 37.4% of V122I carriers having at least one of these manifestations by age 75. Our findings show that V122I carriers are at increased risk of polyneuropathy. These results also emphasize the underdiagnosis of disease in V122I carriers with a significant proportion of subjects showing phenotypic changes consistent with hATTR amyloidosis. Greater understanding of the manifestations associated with V122I is critical for earlier diagnosis and treatment.
SARS-CoV-2 diagnostic practices broadly involve either quantitative polymerase chain reaction (qPCR)-based nucleic amplification of viral sequences or antigen-based tests such as lateral flow assays ...(LFAs). Reverse transcriptase-qPCR can detect viral RNA and is the gold standard for sensitivity. However, the technique is time-consuming and requires expensive laboratory infrastructure and trained staff. LFAs are lower in cost and near real time, and because they are antigen-based, they have the potential to provide a more accurate indication of a disease state. However, LFAs are reported to have low real-world sensitivity and in most cases are only qualitative. Here, an antigen-based electrochemical aptamer sensor is presented, which has the potential to address some of these shortfalls. An aptamer, raised to the SARS-CoV-2 spike protein, was immobilized on a low-cost gold-coated polyester substrate adapted from the blood glucose testing industry. Clinically relevant detection levels for SARS-CoV-2 are achieved in a simple, label-free measurement format using sample incubation times as short as 15 min on nasopharyngeal swab samples. This assay can readily be optimized for mass manufacture and is compatible with a low-cost meter.
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