A case of metastatic melanoma in the liver mimicking colorectal cancer with synchronous liver metastasis.

INTRODUCTION AND IMPORTANCE: Colorectal cancer (CRC) presenting with synchronous liver metastasis is relatively common, occurring in approximately 20 % of patients1. Herein we report an atypical case of a patient who presented with a new, obstructing colon mass with synchronous liver metastasis, biopsy proven to be malignant melanoma. CASE PRESENTATION: An 81-year-old male presented to the hospital emergency department with abdominal pain, diarrhea, and 30-pound unintentional weight loss over the past 4 months. Investigations revealed an obstructing cecal mass with multiple large, hypodense hepatic masses suspicious for metastatic disease. A multidisciplinary evaluation ensued, and the decision was made to treat with palliative intent. The patient was surgically treated with a diverting stoma and an intraoperative biopsy of the hepatic masses demonstrated metastatic melanoma. The patient did report a remote history of malignant melanoma and underwent curative-intent resection a decade earlier. There was no evidence of a new primary cutaneous melanoma. A tentative plan for checkpoint inhibitor therapy was discussed, but his medical issues worsened, and the patient died before any anti-cancer therapy could be started. CLINICAL DISCUSSION: The clinical picture of obstructing colon mass with synchronous liver masses most commonly represents a colon primary with synchronous liver metastasis. The capacity for melanoma to mimic other pathologies is unusual but has been described, with case reports describing metastasis to the eye, biliary hilum, liver, pancreas, colon, small bowel, and brain. This case serves as a good reminder that melanoma may mimic a variety of oncologic presentations, even after a very long disease-free interval. CONCLUSION: Our patient suspected to have metastatic colon cancer was found instead to have metastatic melanoma, with significantly different therapeutic options and prognosis.

Fatigue in children who have recently completed treatment for acute lymphoblastic leukemia: a longitudinal study.

BACKGROUND: This study examined fatigue in patients treated for childhood acute lymphoblastic leukemia (ALL) over a 2-year period (3- to 27-months post-treatment completion), from the perspective of children and parent caregivers, compared to a healthy comparison group. METHODS: Eighty-three patients (4-16 years at enrolment) and their parents, reported on the child's fatigue using the Pediatric Quality of Life Inventory- Multidimensional Fatigue Scale (PedsQL-MFS), at 3- 15- and 27-months post-treatment completion, and 53 healthy children and their parents reported on fatigue across the same timepoints. RESULTS: Parent proxy-reporting showed that parents of ALL patients reported more total fatigue than parents of the comparison group at all time points, with all subscales elevated (general, cognitive, and sleep/rest fatigue). In contrast, patient self-report of fatigue over this period differed from the comparison children for the general fatigue subscale only. Self-reported total fatigue was worse than the comparison group at the 27-month timepoint, with cognitive and sleep/rest fatigue symptoms contributing to this difference. Expected improvements in fatigue over time were not evident in either patient or parent report and no demographic risk factors were identified. Parents and children from both groups reported significantly more fatigue at all time points compared to commonly utilised normative population data. CONCLUSIONS: Patients treated for childhood ALL are impacted by fatigue symptoms in the post-treatment and early survivorship period. These findings highlight that patients in the 2-years following treatment require increased symptom surveillance and may benefit particularly from interventions that target cognitive and sleep/rest fatigue.

Vascular access device type for systemic anti-cancer therapies in cancer patients: A scoping review.

BACKGROUND: Patients with cancer can expect to receive numerous invasive vascular access procedures for intravenous therapy and clinical diagnostics. Due to the increased incidence and prevalence of cancer globally there will be significantly more people who require first-line intravenous chemotherapy over the next ten years. METHODS: Our objective was to determine the types of evidence that exist for the vascular access device (VAD) type for the delivery of systemic anti-cancer therapy (SACT) in cancer patients. We used JBI scoping review methodology to identify the types of VADs used for SACT and with a specific search strategy included articles from 2012-2022 published in the English language. We identify (i) type of VADs used for SACT delivery (ii) the type of insertion and post-insertion complications (iii) the geographical location and clinical environment (iv) and whether VAD choice impacts on quality of life (QOL). Findings were presented using the PAGER framework. MAIN FINDINGS: Our search strategy identified 10,390 titles, of these, 5318 duplicates were removed. The remaining 5072 sources were screened for eligibility, 240 articles met the inclusion criteria. The most common design include retrospective study designs (n = 91) followed by prospective study designs (n = 31). We found 28 interventional studies with 21 registered in a clinical trial registry and identified no core outcome sets papers specific to VAD for SACT. The most prevalent publications were those that featured two or more VAD types (n = 70), followed by tunnelled intravenous VADs (n = 67). Of 38 unique complications identified, the most frequent catheter related complication was catheter related thrombosis (n = 178, 74%), followed by infection (n = 170, 71%). The county where the most publications originated from was China (n = 62) with one randomized controlled multicenter study from a comprehensive cancer centre. Of the thirty three studies that included QOL we found 4 which reported on body image. No QOL measurement tools specific to the process of SACT administration via VAD are available INTERPRETATION: Our findings suggest a systematic review and meta-analysis of VAD use for intravenous SACT can be considered. However, the development of a core outcome set for SACT should be prioritised. Funding for high quality programs of research for VAD in cancer are needed. Comprehensive cancer centres should lead this research agenda.

Gene expression of hepatic gluconeogenic and fatty acid metabolism in early-lactation dairy cows as affected by dietary starch and monensin supplementation.

Our previously published companion papers demonstrated improved production performance and energetic metabolism in cows fed diets with increased propiogenic potential in early lactation. Study objectives were to further explore effects of dietary starch content and monensin on hepatic gene expression of key enzymes related to gluconeogenesis and fatty acid metabolism in early lactation. From d 1 to 21 postpartum, primiparous (n = 16) and multiparous (n = 33) Holstein cows were fed a high (HS; 26.2% starch, 34.3% neutral detergent fiber, 22.7% acid detergent fiber, 15.5% crude protein) or low (LS; 21.5% starch, 36.9% neutral detergent fiber, 25.2% acid detergent fiber, 15.4% crude protein) starch diet with a daily topdress containing either 0 (Con) or 450 mg/d monensin (Mon). Cows were randomly assigned to treatment. Liver biopsies were obtained from cows on d 7 postpartum for DNA and RNA quantification and mRNA expression analysis. In primiparous cows, Mon supplementation decreased CPT1A expression relative to controls, whereas in multiparous cows Mon increased its expression. Cows fed HS and Mon tended to have decreased HMGCS2 expression relative to cows fed HS and Con. In multiparous cows, Mon supplementation tended to increase PC and PCK1 expression relative to controls. Correlation analysis was performed for all gene expression variables. Overall, relationships were similar in directionality and magnitude between cows fed HS and LS and Con and Mon. However, for cows fed Con there was a positive relationship between HMGCS2 and PC and HMGCS2 and PCK1, whereas for cows fed Mon there was no relationship. There was a similar lack of relationship between HMGCS2 and PC for cows fed HS. Overall, results support changes in performance and energetic metabolism reported in our companion papers, indicating that cows fed diets of different starch content in early lactation with Mon supplementation throughout the transition period had alterations in hepatic gene expression consistent with increased hepatic propionate supply.

Tropical decadal variability in nutrient supply and phytoplankton community in the Central Equatorial Pacific during the late Holocene.

We have reconstructed baseline δ15N and δ13C of export production at Kingman Reef in the Central Equatorial Pacific (CEP) at sub-decadal resolution, nearly continuously over the last 2000 years. The changes in δ15N reflects the strength of the North Equatorial Counter Current (NECC) relative to the South Equatorial Current (SEC), and to a lesser extent, the North Equatorial Current (NEC). Seasonal to multi-decadal variation in the strength of these currents, through the redistribution of heat, have global climate impacts and influence marine and terrestrial ecosystems. We use modern El Niño-La Nina dynamics and the Tropical Pacific Decadal Variability (TPDV) pattern, which is defined in the CEP, as a framework for analyzing the isotopic data. The CEP δ15N and δ13C records exhibit multi-decadal (50-60 year) variability consistent with TPDV. A large multi-centennial feature in the CEP δ15N data, within age-model uncertainties, is consistent with one of the prolonged dry-pluvial sequences in the American west at the end of the Medieval Climate Anomaly, where low TPDV is correlated with drier conditions. This unique record shows that the strength of the NECC, as reflected in baseline δ15N and δ13C, has at quasi-predictable intervals throughout the late Holocene, toggled the phytoplankton community between prokaryotes and picoplankton versus eukaryotes.

Defining quality assessment in vascular surgery training: an expert Delphi process.

INTRODUCTION: A robust and reproducible way of assessing training should optimise and standardise vascular surgical training. This study describes the methodology supporting the Vascular Surgery Specialty Advisory Committee regional quality assurance reports for vascular surgery training programmes in the UK. METHODS: A Delphi consensus exercise was performed to establish the domains of training that most appropriately assess the quality of a vascular surgery training programme. A total of 54 stakeholders were invited to participate, including trainees, training programme directors and members of the vascular speciality advisory committee (SAC), vascular society executive and education committees. RESULTS: A total of 39 stakeholders successfully completed the three-stage Delphi process over 15 weeks. The domains identified as most appropriate to assess the quality of a vascular training programme were: Joint Committee on Surgical Training (JCST) survey results, clinical experience, regional education programmes, radiology support, timetable, regional support for trainees, trainer support for trainees, opportunities for professional development, trainee-rated quality of consultant teaching and training, and trainee recommendation of the post. CONCLUSIONS: This study describes a method to identify and prioritise domains that are appropriate to assess the quality of a vascular training programme. The domains that were identified as appropriate to assess quality are transferable internationally and the Delphi methodology could be used by other training schemes to 'fine-tune' their own domains to review and optimise the quality of their own training programmes.

Protecting workers in the temporary staffing industry.

BACKGROUND: Workers hired through temporary staffing companies have a high rate of severe and fatal injuries despite the legally mandated, shared responsibility of the temporary staffing company and the host company to assure safe work. AIMS: The aim of this study was to elucidate the perspective of temporary staffing personnel on approaches to mitigating injury risk among the workers they hire. METHODS: Based on a conceptual model representing the interplay between work and health, we conducted a 'brainstorm' of temporary staffing personnel regarding perceived barriers to protecting temporary workers. A content/context analysis used standard qualitative methods, and the findings were triangulated with notes taken during the discussion. RESULTS: Temporary staffing employers describe loss of control of the working conditions once workers are placed at host/client companies. Further, they describe a contentious relationship between temporary staffing and host companies, where it is difficult to hold host companies to account. Other barriers to providing temporary workers with a safe work environment include the temp companies' lack of knowledge of site-specific hazards, the poor quality of onsite Occupational Safety and Health training, and ignoring Occupational Safety and Health Administration (OSHA) requirements. CONCLUSIONS: The perspective of temporary staffing companies should be considered to address the lack of cooperation and shifted responsibility described in this study. Policy and practice changes could include requiring contract language, implementing communication about safety, either sharing workers' compensation purchase or removing exclusive remedy protections from hosts, and prescribing safety training, such as an OSHA 10-h programme. Suggested interventions need further study.

Atmospheric molecular blobs shape up circumstellar envelopes of AGB stars.

During their thermally pulsing phase, asymptotic giant branch (AGB) stars eject material that forms extended dusty envelopes1. Visible polarimetric imaging found clumpy dust clouds within two stellar radii of several oxygen-rich stars2-6. Inhomogeneous molecular gas has also been observed in multiple emission lines within several stellar radii of different oxygen-rich stars, including W Hya and Mira7-10. At the stellar surface level, infrared images have shown intricate structures around the carbon semiregular variable R Scl and in the S-type star π1 Gru11,12. Infrared images have also shown clumpy dust structures within a few stellar radii of the prototypical carbon AGB star IRC+10°216 (refs. 13,14), and studies of molecular gas distribution beyond the dust formation zone have also shown complex circumstellar structures15. Because of the lack of sufficient spatial resolution, however, the distribution of molecular gas in the stellar atmosphere and the dust formation zone of AGB carbon stars is not known, nor is how it is subsequently expelled. Here we report observations with a resolution of one stellar radius of the recently formed dust and molecular gas in the atmosphere of IRC+10°216. Lines of HCN, SiS and SiC2 appear at different radii and in different clumps, which we interpret as large convective cells in the photosphere, as seen in Betelgeuse16. The convective cells coalesce with pulsation, causing anisotropies that, together with companions17,18, shape its circumstellar envelope.

The atmospheric X-ray imaging spectrometer (AXIS) instrument: Quantifying energetic particle precipitation through bremsstrahlung X-ray imaging.

The Atmospheric X-ray Imaging Spectrometer (AXIS) described in this work is a compact, wide field-of-view, hard x-ray imager. The AXIS instrument will fly onboard the Atmospheric Effects of Precipitation through Energetic X-rays (AEPEX) 6U CubeSat mission and will measure bremsstrahlung x-ray photons in the 50-240 keV range with cadmium-zinc-telluride (CZT) detectors using coded aperture optics. AXIS will measure photons generated by energetic particle precipitation for the purpose of determining the spatial scales of precipitation and estimating electron precipitation characteristics. This paper describes the design and testing of the AXIS instrument, including a summary of simulations performed that motivate the shielding, optics, and mechanical design. Testing and characterization is reported that validates the instrument design and shows that the instrument design meets or exceeds the measurement requirements necessary for AEPEX mission success.

Machine learned interatomic potential for dispersion strengthened plasma facing components.

Tungsten (W) is a material of choice for the divertor material due to its high melting temperature, thermal conductivity, and sputtering threshold. However, W has a very high brittle-to-ductile transition temperature, and at fusion reactor temperatures (≥1000 K), it may undergo recrystallization and grain growth. Dispersion-strengthening W with zirconium carbide (ZrC) can improve ductility and limit grain growth, but much of the effects of the dispersoids on microstructural evolution and thermomechanical properties at high temperatures are still unknown. We present a machine learned Spectral Neighbor Analysis Potential for W-ZrC that can now be used to study these materials. In order to construct a potential suitable for large-scale atomistic simulations at fusion reactor temperatures, it is necessary to train on ab initio data generated for a diverse set of structures, chemical environments, and temperatures. Further accuracy and stability tests of the potential were achieved using objective functions for both material properties and high temperature stability. Validation of lattice parameters, surface energies, bulk moduli, and thermal expansion is confirmed on the optimized potential. Tensile tests of W/ZrC bicrystals show that although the W(110)-ZrC(111) C-terminated bicrystal has the highest ultimate tensile strength (UTS) at room temperature, observed strength decreases with increasing temperature. At 2500 K, the terminating C layer diffuses into the W, resulting in a weaker W-Zr interface. Meanwhile, the W(110)-ZrC(111) Zr-terminated bicrystal has the highest UTS at 2500 K.

Associations of a liver health index with health, milk yield, and reproductive performance in dairy herds in the northeastern United States.

The objective was to evaluate a liver health index (LHI) by evaluating its association with negative health events, milk yield, and risk of pregnancy within 150 d in milk (DIM). In a retrospective cohort study, an LHI was calculated based on plasma albumin, cholesterol, and bilirubin concentrations for 265 primiparous and 611 multiparous cows 3 to 12 DIM enrolled across 72 farms in the northeastern United States. Mixed effects linear regression models were used to evaluate if (1) metritis (MET), (2) displaced abomasum (DA), (3) clinical ketosis (CK), (4) one or more of the 3 disorders (MET, DA, or CK), (5) 2 or more of the 3 disorders (MET, DA, or CK), or (6) culling within 30 DIM was associated with LHI. Mixed effects linear regression models were used to evaluate if LHI was associated with 305-d mature equivalent milk at the fourth test day (ME305; mean ± standard deviation: 114 ± 13 DIM) and a Cox proportional hazards model was used to evaluate if LHI was associated with pregnancy within 150 DIM. Cows that were diagnosed with MET, DA, CK, one or more of the disorders, 2 or more of the disorders, or were culled within 30 DIM had a lower LHI than cows that were not diagnosed with a disorder or culled. A 1-unit increase in LHI was associated with a 154 ± 38 kg increase in ME305 and a 8% increased risk of pregnancy within 150 DIM [hazard ratio (95% confidence interval): 1.08 (1.03 to 1.14)] for multiparous cows; however, we did not identify a relationship between LHI and ME305 or pregnancy within 150 DIM for primiparous cows. These results suggest that the LHI is associated with health, milk yield, and pregnancy within 150 DIM for multiparous cows and health for primiparous cows; therefore, the LHI can be used as a tool to evaluate transition cow success.

Optimizing the use of Paxlovid in clinical practice.

On December 22, 2021, the United States Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for nirmatrelvir/ritonavir (Paxlovid) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). The drug is authorized for use in patients 12 years of age and older weighing at least 40 kg who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and who are at high risk for progression to severe COVID-19. Nirmatrelvir, an orally bioavailable protease inhibitor that prevents SARS-CoV-2 replication by cleaving the two viral polyproteins, is packaged with ritonavir, a cytochrome P450 (CYP)3A4 inhibitor and pharmacokinetic boosting agent that increases nirmatrelvir concentrations. Although Paxlovid has demonstrated clinical efficacy in unvaccinated patients with COVID-19, its role in the treatment of other populations is less clear. This manuscript reviews what is known about Paxlovid and explores how this drug may be used in the future to treat patients with SARS-CoV-2 infection.

Public beliefs about the consequences of living with obesity in the Republic of Ireland and Northern Ireland.

BACKGROUND: This study aimed to capture public beliefs about living with obesity, examine how these beliefs have changed over time and to explore whether certain characteristics were associated with them in a nationally representative sample of adults from the Republic of Ireland (RoI) and Northern Ireland (NI). METHODS: A cross-sectional survey employed a random quota sampling approach to recruit a nationally representative sample of 1046 adults across NI and RoI. Telephone interviews captured information on demographics; health behaviours & attitudes; and beliefs about the consequences of obesity (measured using the Obesity Beliefs Scale). Univariable analyses compared beliefs about the consequences of living with obesity between participants with a self-reported healthy weight and those living with overweight or obesity, and non-responders (those for whom weight status could not be ascertained due to missing data). Multiple linear regression examined associations between obesity-related beliefs and socio-demographics, self-rated health and perceived ability to change health behaviours. Multiple linear regression also compared changes in obesity-related beliefs between 2013 and 2020 in the RoI. RESULTS: Higher endorsement of the negative outcomes of obesity was significantly associated with living with a healthy weight, higher self-rated health, dietary quality and perceived ability to improve diet and physical activity. Those who lived with overweight, with obesity and non-responders were less likely to endorse the negative consequences of obesity. Those living with obesity and non-responders were also more likely to support there is an increased cost and effort in maintaining a healthy weight. Comparison with survey data from 2013 showed that currently, there is a greater endorsement of the health benefits of maintaining a healthy weight (p < 0001), but also of the increased costs associated with it (p < 0001). CONCLUSION: Beliefs about the consequences of maintaining a healthy body weight are associated with individuals' weight, self-rated health, diet and perceived ease of adoption of dietary and exercise-related improvements. Beliefs about the health risks of obesity and perceived greater costs associated with maintaining a healthy weight appear to have strengthened over time. Present findings are pertinent to researchers and policy makers involved in the design and framing of interventions to address obesity.

Prevalence of bacterial burden on macroscopic contaminants of orthopaedic surgical instruments following sterilization.

BACKGROUND: Macroscopic contamination of orthopaedic instruments with particulates, including cortical bone and polymethyl methacrylate (PMMA) bone cement, that have previously undergone pre-operative sterilization is frequently encountered peri- or intraoperatively, calling into question the sterility of such instruments. AIM: To determine if macroscopic contaminants of orthopaedic surgical instrumentation maintain a bacterial burden following sterile processing, and to determine the most commonly contaminated instruments and the most common contaminants. METHODS: Macroscopic contaminants in orthopaedic instrument trays were collected prospectively at a single tertiary referral centre over a 6-month period from August 2021 to May 2022. When identified, these specimens were swabbed and plated on sheep blood agar. All specimens were incubated at 37 °C for 14 days, and inspected visually for colony formation. When bacterial colony formation was identified, samples were sent for species identification. RESULTS: In total, 33 contaminants were tested, and only one contaminant was found to be growing bacterial colonies (Corynebacterium sp.). The items most commonly found to have macroscopic contamination were surgical trays (N=9) and cannulated drills (N=7). The identifiable contaminants were bone (N=10), PMMA bone cement (N=4) and hair (N=4). Eleven macroscopic contaminants were not identifiable. CONCLUSION: This study found that 97% of macroscopic orthopaedic surgical instrument contaminants that underwent sterile processing did not possess a bacterial burden. Contaminants discovered during a procedure are likely to be sterile, and do not pose a substantially increased risk of infection to a patient.

Active Precipitation of Radiation Belt Electrons Using Rocket Exhaust Driven Amplification (REDA) of Man-Made Whistlers.

Ground-based very low frequency (VLF) transmitters located around the world generate signals that leak through the bottom side of the ionosphere in the form of whistler mode waves. Wave and particle measurements on satellites have observed that these man-made VLF waves can be strong enough to scatter trapped energetic electrons into low pitch angle orbits, causing loss by absorption in the lower atmosphere. This precipitation loss process is greatly enhanced by intentional amplification of the whistler waves using a newly discovered process called rocket exhaust driven amplification (REDA). Satellite measurements of REDA have shown between 30 and 50 dB intensification of VLF waves in space using a 60 s burn of the 150 g/s thruster on the Cygnus satellite that services the International Space Station. This controlled amplification process is adequate to deplete the energetic particle population on the affected field lines in a few minutes rather than the multi-day period it would take naturally. Numerical simulations of the pitch angle diffusion for radiation belt particles use the UCLA quasi-linear Fokker Planck model to assess the impact of REDA on radiation belt remediation of newly injected energetic electrons. The simulated precipitation fluxes of energetic electrons are applied to models of D-region electron density and bremsstrahlung X-rays for predictions of the modified environment that can be observed with satellite and ground-based sensors.

Modulation, microbiota and inflammation in the adult CF gut: A prospective study.

BACKGROUND: Cystic Fibrosis (CF) has prominent gastrointestinal and pancreatic manifestations. The aim of this study was to determine the effect of Cystic fibrosis transmembrane conductance regulator (CFTR) modulation on, gastrointestinal inflammation, pancreatic function and gut microbiota composition in people with cystic fibrosis (CF) and the G551D-CFTR mutation. METHODS: Fourteen adult patients with the G551D-CFTR mutation were assessed clinically at baseline and for up to 1 year after treatment with ivacaftor. The change in gut inflammatory markers (calprotectin and lactoferrin), exocrine pancreatic status and gut microbiota composition and structure were assessed in stool samples. RESULTS: There was no significant change in faecal calprotectin nor lactoferrin in patients with treatment while all patients remained severely pancreatic insufficient. There was no significant change in gut microbiota diversity and richness following treatment. CONCLUSION: There was no significant change in gut inflammation after partial restoration of CFTR function with ivacaftor, suggesting that excess gut inflammation in CF is multi-factorial in aetiology. In this adult cohort, exocrine pancreatic function was irreversibly lost. Longer term follow-up may reveal more dynamic changes in the gut microbiota and possible restoration of CFTR function.

Growth rates of contract-reared versus home-reared replacement dairy heifers.

Successful heifer rearing is dependent on achieving optimal average daily gain (ADG) targets to calve for the first time at 24 months. Whilst dairy farmers internationally have traditionally managed their heifers on-farm to achieve these targets, recent dairy herd expansion within Europe has resulted in increased demand for labour-saving heifer-rearing strategies, such as off-farm contractrearing. However, loss of direct influence on the day-to-day management decisions affecting the ability of heifers to grow adequately to achieve this age of first calving may represent a potential barrier to uptake. Hence, the aim of this longitudinal observational study was to compare the growth rates of contract- vs home-reared heifers. Approximately 6 500 heifers from 120 commercial Irish dairy farms were enrolled in a 3-year study. For 65 of these farms, heifers were reared at a contract-rearing facility. For the remaining 55 farms, heifers were reared on their home farm. Over the course of 20 months from birth until precalving, heifers were examined and weighed at four farm visits. The relationship between several independent variables (farm type, herd size, heifer breed, economic breeding index (EBI) and health events) and ADG at different time points was investigated and analysed utilising linear mixed models. Overall ADG for heifers throughout the rearing period was 0.71 kg/day. There was a significant association between farm type and ADG for all five linear ADG models; home-reared heifers grew, on average, 0.025, 0.039, 0.11 and 0.059 kg/day more than contract-reared heifers between visit 1 and visit 4 (overall ADG), visit 1 and visit 2, visit 2 and visit 3 and visit 1 and visit 3, respectively. The occurrence of diarrhoea during farm visit 2 (median age 8.5 months) was associated with a significant reduction in ADG between visit 3 and visit 4. Calf-hood disease (diarrhoea, respiratory disease or navel ill) was not associated with the growth rate during any of the subsequent visit periods. While home-reared heifers had greater ADG during four of the five periods studied, median heifer ADG in both cohorts exceeded the minimum published target weight gains at each developmental stage required for heifers to reach puberty, conceive at 15 months and calve for the first time at 24 months. Importantly, there was wide variation both within enterprises and between farms. It was concluded that while the absolute difference in daily growth rates of home- and contract-reared heifers was minimal, when considered in the context of the entire heifer-rearing period, these growth rate differences have the potential to impact the future reproductive and milk production performance of heifers.

Neurogenesis in the neonatal rat hippocampus is regulated by sexually dimorphic epigenetic modifiers.

BACKGROUND: Neurogenesis in the hippocampus endures across the lifespan but is particularly prolific during the first postnatal week in the developing rodent brain. The majority of new born neurons are in the dentate gyrus (DG). The number of new neurons born during the first postnatal week in the DG of male rat pups is about double the number in females. In other systems, the rate of cell proliferation is controlled by epigenetic modifications in stem cells. We, therefore, explored the potential impact of DNA methylation and histone acetylation on cell genesis in the developing DG of male and female rats. METHODS: Cell genesis was assessed by quantification of BrdU + cells in the DG of neonatal rats following injections on multiple days. Methylation and acetylation were manipulated pharmacologically by injection of well vetted drugs. DNA methylation, histone acetylation and associated enzyme activity were measured using commercially available colorimetric assays. mRNA was quantified by PCR. Multiple group comparisons were made by one- or two-way ANOVA followed by post-hoc tests controlling for multiple comparisons. Two groups were compared by t test. RESULTS: We found higher levels of DNA methylation in male DG and treatment with the DNA methylating enzyme inhibitor zebularine reduced the methylation and correspondingly reduced cell genesis. The same treatment had no impact on either measure in females. By contrast, treatment with a histone deacetylase inhibitor, trichostatin-A, increased histone acetylation in the DG of both sexes but increased cell genesis only in females. Females had higher baseline histone deacetylase activity and greater inhibition in response to trichostatin-A treatment. The mRNA levels of the proproliferative gene brain-derived neurotrophic factor were greater in males and reduced by inhibiting both DNA methylation and histone deacetylation only in males. CONCLUSIONS: These data reveal a sexually dimorphic epigenetically based regulation of neurogenesis in the DG but the mechanisms establishing the distinct regulation involving DNA methylation in males and histone acetylation in females is unknown.

A survey of biosecurity and health management practices on Irish dairy farms engaged in contract-rearing.

A survey was conducted to investigate potential differences in biosecurity and health management practices on Irish dairy farms that sent their heifers for contract-rearing (source dairy farms, SDF; n = 62) and those rearing their own heifers (control farms, CF; n = 50). Participating farmers were surveyed by postal questionnaire between September and November 2018. The overall response rate was 93%. Results show that structurally, SDF were larger, less fragmented, and more specialized than CF. Outsourcing of labor-intensive activities to external contractors was more common among SDF than CF, exposing them to potentially increased biosecurity risks associated with animal movements, use of shared equipment, and increased frequency of farm visitors. The majority of SDF sent heifers to a single-origin rearing facility (70%), with heifers most commonly arriving at the rearing unit between 2 and 4 mo (53%) and returning to the dairy farm between 18 and 21 mo of age (56%). Despite the increased biosecurity risk associated with contract-rearing, implementation of disease prevention measures was not superior on SDF compared with CF. For both farm types, there was scope for improvement to visitor biosecurity protocols, quarantine procedures, colostrum feeding practices, and hygiene of calving areas. This research provides an overview of the demographics and farm management practices implemented by dairy farmers engaged in contract-rearing of replacement heifers, and will serve to inform farmers, veterinary advisors, and policy makers.

Interannual Dynamics of Ice Cliff Populations on Debris-Covered Glaciers From Remote Sensing Observations and Stochastic Modeling.

Ice cliffs are common on debris-covered glaciers and have relatively high melt rates due to their direct exposure to incoming radiation. Previous studies have shown that their number and relative area can change considerably from year to year, but this variability has not been explored, in part because available cliff observations are irregular. Here, we systematically mapped and tracked ice cliffs across four debris-covered glaciers in High Mountain Asia for every late ablation season from 2009 to 2019 using high-resolution multi-spectral satellite imagery. We then quantified the processes occurring at the feature scale to train a stochastic birth-death model to represent the cliff population dynamics. Our results show that while the cliff relative area can change by up to 20% from year to year, the natural long-term variability is constrained, thus defining a glacier-specific cliff carrying capacity. In a subsequent step, the inclusion of external drivers related to climate, glacier dynamics, and hydrology highlights the influence of these variables on the cliff population dynamics, which is usually not a direct one due to the complexity and interdependence of the processes taking place at the glacier surface. In some extreme cases (here, a glacier surge), these external drivers may lead to a reorganization of the cliffs at the glacier surface and a change in the natural variability. These results have implications for the melt of debris-covered glaciers, in addition to showing the high rate of changes at their surface and highlighting some of the links between cliff population and glacier state.