Short communication: Temporal profiles of colostrum and milk haptoglobin and substance P in early lactation multiparous Holstein cows.

Milk markers have the potential to aid in the detection of cow disease in early lactation if the automation of milk analysis becomes commonplace. Characterising temporal profiles of milk markers in dairy cows will improve the understanding of basal concentrations in clinically healthy cows. The objective of this observational study was to characterise the variation and temporal profiles of colostrum and milk haptoglobin (Hp) and substance P concentrations within 21 days postcalving in clinically healthy multiparous Holstein dairy cows. Ninety Holstein dairy cows from a commercial dairy herd were included. Milk samples were collected on the day of calving (day 0), and on days 1 to 4, 7, 14, and 21 postcalving and concentrations of Hp and substance P in colostrum (days 0 to 3) and milk (days 4, 7, 14, and 21) were determined using Enzyme Linked Immunosorbent assay. Haptoglobin and substance P concentrations were, on average (raw means ± SD), 0.40 ± 0.26 µg/ml and 56.2 ± 38.7 pg/ml in colostrum, respectively, and 0.23 ± 0.23 µg/ml and 37.1 ± 27.8 pg/ml in milk, respectively. Haptoglobin and substance P were elevated and greatest 1 day postcalving (least squares mean ± SE of the mean; 0.53 ± 0.05 µg/ml and 46.5 ± 3.64 pg/ml, respectively) and substance P varied widely within 21 days postcalving. The presence of substance P in dairy cow colostrum was not documented previously. Elevated concentrations of Hp and substance P immediately postcalving may be due to physiological roles these inflammatory markers have in the dairy cow or neonate or may simply represent an accumulation in colostrum before the first milk is removed.

Mutations in DARS2 result in global dysregulation of mRNA metabolism and splicing.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare neurological disorder caused by the mutations in the DARS2 gene, which encodes the mitochondrial aspartyl-tRNA synthetase. The objective of this study was to understand the impact of DARS2 mutations on cell processes through evaluation of LBSL patient stem cell derived cerebral organoids and neurons. We generated human cerebral organoids (hCOs) from induced pluripotent stem cells (iPSCs) of seven LBSL patients and three healthy controls using an unguided protocol. Single cells from 70-day-old hCOs were subjected to SMART-seq2 sequencing and bioinformatic analysis to acquire high-resolution gene and transcript expression datasets. Global gene expression analysis demonstrated dysregulation of a number of genes involved in mRNA metabolism and splicing processes within LBSL hCOs. Importantly, there were distinct and divergent gene expression profiles based on the nature of the DARS2 mutation. At the transcript level, pervasive differential transcript usage and differential spliced exon events that are involved in protein translation and metabolism were identified in LBSL hCOs. Single-cell analysis of DARS2 (exon 3) showed that some LBSL cells exclusively express transcripts lacking exon 3, indicating that not all LBSL cells can benefit from the "leaky" nature common to splice site mutations. At the gene- and transcript-level, we uncovered that dysregulated RNA splicing, protein translation and metabolism may underlie at least some of the pathophysiological mechanisms in LBSL. To confirm hCO findings, iPSC-derived neurons (iNs) were generated by overexpressing Neurogenin 2 using lentiviral vector to study neuronal growth, splicing of DARS2 exon 3 and DARS2 protein expression. Live cell imaging revealed neuronal growth defects of LBSL iNs, which was consistent with the finding of downregulated expression of genes related to neuronal differentiation in LBSL hCOs. DARS2 protein was downregulated in iNs compared to iPSCs, caused by increased exclusion of exon 3. The scope and complexity of our data imply that DARS2 is potentially involved in transcription regulation beyond its canonical role of aminoacylation. Nevertheless, our work highlights transcript-level dysregulation as a critical, and relatively unexplored, mechanism linking genetic data with neurodegenerative disorders.

The development and validation of a nationwide dataset of water distribution zones in Aotearoa New Zealand: A cross-sectional geospatial study.

The reliable supply of safe drinking water is vital for the health of human populations. Despite this, there is no consistent nationwide spatial dataset of water distribution zones (WDZ) for Aotearoa New Zealand (A-NZ). The purpose of this data article is to describe the development and validation of a consistent nationwide dataset of WDZ across A-NZ. We obtained spatial data from all 67 district and city councils through: 1) information requests between 2021 and 2023; 2) the Ministry of Health and; 3) the Institute of Environmental Science and Research. Data were modified to improve the spatial accuracy of the WDZ using auxiliary data on the building footprints (Land Information New Zealand) and the drinking water reticulation (WSP & councils). We estimated the population served by each WDZ through spatial linking to meshblock-level data provided by Statistics New Zealand (meshblocks are the smallest administrative geographic unit in A-NZ). The dataset will be useful to provide insights into the extent of the publicly-owned drinking water assets in A-NZ and is essential for the accurate exposure assessment in epidemiological research investigating the impact of drinking water quality on human health.

Repeated transmission of SARS-CoV-2 in an overcrowded Irish emergency department elucidated by whole-genome sequencing.

AIM: To provide a detailed genomic-epidemiological description of a complex multi-ward SARS-CoV-2 outbreak, which originated in the crowded emergency department (ED) in our hospital during the third wave of the COVID-19 pandemic, and was elucidated promptly by local whole-genome sequencing (WGS). METHODS: SARS-CoV-2 was detected by reverse transcriptase real-time polymerase chain reaction on viral RNA extracted from nasopharyngeal swabs. WGS was performed using an Oxford MinION Mk1C instrument following the ARTIC v3 sequencing protocol. High-quality consensus genomes were assembled with the artic-ncov2019 bioinformatics pipeline and viral phylogenetic trees were built, inferred by maximum-likelihood. Clusters were defined using a threshold of 0-1 single nucleotide polymorphisms (SNPs) between epidemiologically linked sequences. RESULTS: In April 2021, outbreaks of COVID-19 were declared on two wards at University Hospital Limerick after 4 healthcare-associated SARS-CoV-2 infections were detected by post-admission surveillance testing. Contact tracing identified 12 further connected cases; all with direct or indirect links to the ED 'COVID Zone'. All sequences were assigned to the Pangolin B.1.1.7 lineage by WGS, and SNP-level analysis revealed two distinct but simultaneous clusters of infections. Repeated transmission in the ED was demonstrated, involving patients accommodated on trolleys in crowded areas, resulting in multiple generations of infections across three inpatient hospital wards and subsequently to the local community. These findings informed mitigation efforts to prevent cross-transmission in the ED. CONCLUSION: Cross-transmission of SARS-CoV-2 occurred repeatedly in an overcrowded emergency department. Viral WGS elucidated complex viral transmission networks in our hospital and informed infection, prevention and control practice.

An examination of labor time-use on spring-calving dairy farms in Ireland.

The seasonal workload associated with pasture-based dairy farms, combined with increasing herd sizes, has led to a renewed focus on labor time-use and efficiency on dairy farms. The objective of this study was to examine labor time-use on pasture-based dairy farms in the spring and summer seasons. A total of 82 spring-calving Irish dairy farms completed the study from February 1 to June 30, 2019 (150 d). Each farmer recorded their labor input on one alternating day each week using a smartphone app. Any labor input by farm workers not using the app was recorded through a weekly online survey. Farms with data for each month (n = 76) were classified into 1 of 4 herd size categories (HSC) for analysis: farms with 50 to 90 cows (HSC 1); 91 to 139 cows (HSC 2); 140 to 239 cows (HSC 3); and ≥240 cows (HSC 4). Total hours of labor input was similar on HSC 1 (1,821 h) and HSC 2 (2,042 h) farms, but predictably as HSC increased further, total hours of labor input increased (HSC 3: 2,462 h, HSC 4: 3,040 h). On a monthly basis, labor input peaked in February (15.4 h/d) and March (15.7 h/d). The farmer worked on average 60.0 h/wk over the duration of the study period. Hired labor and contractors completed a greater amount of work as HSC increased. Labor efficiency, as measured by hours/cow, improved as HSC increased (HSC 1: 26.3 h/cow, HSC 2: 17.7 h/cow, HSC 3: 14.3 h/cow, HSC 4: 10.9 h/cow), though there were large variations in labor efficiency within HSC. Milking was the most time-consuming task, representing 31% of farm labor input making it an important focus for potential improvements in efficiency. The next 5 most time-consuming tasks were calf care (14%), grassland management (13%), cow care (10%), repairs and maintenance (10%), and administration/business (8%). This study contributes to the understanding of labor use during the busiest (most labor demanding) time of the year on pasture-based dairy farms and points to areas where labor efficiency improvements can be made on farms. The considerable variation in farm labor efficiency observed within HSCs emphasizes the necessity for a greater focus on knowledge transfer of methods to achieve improved labor efficiency and a better work-life balance on many dairy farms. As the 2 busiest months on most dairy farms, February and March require the most focus for identification of potential labor savings.

Estimating the effect of different work practices and technologies on labor efficiency within pasture-based dairy systems.

Herd size expansion combined with the seasonal workload on pasture-based dairy farms has led to an increased focus on techniques that can improve farm labor efficiency such as work practices and technologies. The objective of this study was to identify the work practices and technologies associated with labor efficiency of particular tasks, and estimate the time savings that could be made through their implementation during the period of peak labor input on spring-calving dairy farms. Data from an existing labor time-use study, completed from February 1 to June 30, 2019 (150 d), on 76 Irish dairy farms was used in conjunction with a survey on work practice and technology implementation. One hundred ten work practices and technologies were included in the initial survey, and of these, 59 were found to have an association with labor efficiency for their respective tasks. Best practice, regarding labor efficiency, was identified for the 59 work practices and technologies. An accumulation score was compiled for work practice and technology implementation; each farm received one point for each work practice or technology implemented. On average, farms implemented 31 labor-efficient work practices and technologies (ranging from 10-45). The most labor-efficient 25% of farms implemented a greater number of work practices and technologies (n = 37) than the least labor-efficient 25% of farms (n = 25). Multiple regression models estimated that each additional work practice or technology implemented would improve farm labor efficiency by 0.6 h/cow. Additionally, backward-regression models were used to predict the labor-savings associated with the most important work practices and technologies. Labor-savings were estimated for 12 significant individual work practices and technologies, of which 5 were related to milking, 4 to calf care, 2 to cow care, and one to grassland management. The work practices and technologies that offered the largest labor-savings included having one person in the milking pit during the mid-lactation period (-3.04 h/cow), having automatic cluster removers present (-2.55 h/cow) and contracting slurry spreading (-1.78 h/cow). This study focused on the variety of labor-efficient work practices and technologies available and highlighted those that farmers should focus on to improve labor efficiency. The results indicated that there is scope for improvement in the adoption of labor-saving work practices and technologies on many farms. The positive effect of implementing the identified labor-saving techniques on labor efficiency could be used to support future adoption.

The effect of fertilizer nitrogen input to grass-clover swards and calving date on the productivity of pasture-based dairy production.

The objective of this systems-scale study was to investigate grazing season timeframes on pasture and milk production and on milk processability of dairy systems with compact spring-calving dairy cows grazing white clover (Trifolium repens L.) based grassland. Fifty-four primiparous and multiparous Holstein-Friesian dairy cows were used in a one-factor study with 3 systems (n = 18) and repeated over 2 yr (2008/09 and 2009/10). The 3 systems were: early spring calving with annual fertilizer N input of 100 kg·ha-1 applied in spring (ES100N; 2.1 cows·ha-1; grazing February to November), early spring calving without fertilizer N (ES0N; 1.6 cows·ha-1; grazing February to November) and late spring calving without fertilizer N (LS0N; 1.53 cows·ha-1; grazing April to January). Annual pasture production was affected by an interaction between grazing system and year: Mean annual pasture yields for 2008 and 2009 were ES100N; 10.35 and 9.88, ES0N; 8.88 and 8.63, LS0N; 9.18 and 10.31 t of dry matter (DM)·ha-1 (SEM 0.39). LS0N had higher pasture DM yield in 2009 due to higher clover DM production and biological N fixation compared with the other systems. Clover stolon and root mass in the following February was correlated with stolon and root mass in the previous November with 64% of stolon mass present on LS0N in February (R2 = 0.84). There were no detectable differences in per-lactation milk yield (6,335 kg·cow-1), fat, protein and lactose yields (271, 226, 297 kg·cow-1, respectively), cow liveweight (585 kg) or body condition score (3.02). Although winter grazing favored subsequent clover DM production, biological N fixation and pasture DM production, delaying calving date in spring and extending lactation into the following winter led to inefficient use of this pasture by the grazing herd and lowered the quality of late-lactation milk for processing purposes. Hence, a mean calving date in mid- to late-February is recommended for zero-fertilizer N input clover-based grassland.

Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial).

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg-1 based on factor IX) or fresh frozen plasma (15 ml.kg-1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

A multi-terawatt two-color beam for high-power field-controlled nonlinear optics.

Two-color laser beams are instrumental in light-field control and enhancement of high-order harmonic, spectral supercontinuum, and terahertz radiation generated in gases, plasmas, and solids. We demonstrate a multi-terawatt two-color beam produced using a relativistic plasma mirror, with 110 mJ at 800 nm and 30 mJ at 400 nm. Both color components have high spatial quality and can be simultaneously focused, provided that the plasma mirror lies within a Rayleigh range of the driving fundamental beam. Favorable scaling of second-harmonic generation by plasma mirrors at relativistic intensities suggests them as an excellent tool for multi-color waveform synthesis beyond the petawatt level.

BSc nursing & midwifery students experiences of guided group reflection in fostering personal and professional development. Part 2.

Reflective practice is a learning strategy supporting preregistration nursing and midwifery students in meeting everyday clinical practice challenges. This paper reports on a development and innovation evaluation using a qualitative approach exploring students' experiences of guided group reflection organised during fourth year undergraduate internship. Data were collected through student feedback and interviews using a descriptive approach. Three categories emerged from the findings; beginnings for reflective learning, engaging in reflective learning and being a reflective practitioner. Students reported that guided group reflection provided positive opportunities for enhancing confidence. Students demonstrated understanding of reflection and valued reflective time within the closed group structure, which fostered personal and professional development. Findings support the benefits of the established collaborative guided group reflection structures. Guided group reflection is described as a valuable learning strategy on the journey of becoming a nurse in an ever-demanding health care practice world.

Guided group reflection: A question of organisation and support for baccalaureate nursing students: Part1.

This paper focuses on an innovation and development of a guided reflective approach currently offered at a university in Ireland. Significant collaborative structures and processes were created and implemented in providing guided protected reflective time for fourth year pre-registration BSc Nursing and Midwifery students. This initiative is explored within a case study approach. Undergraduate preregistration programmes aim to develop practitioners towards becoming fit for purpose, compassionate and competent in meeting global health care needs. In the current educational literature, there is much about reflection from a theoretical learning stance. Minimum attention has been given to the practicalities surrounding the structures and processes providing learning spaces where reflection can flourish. Reflective practice offers learning opportunities to guide the development of self and practice critical for future learning. Guided reflection is described as an appropriate learning strategy influential in sense making for practice for final year pre-registration BSc undergraduate students.

Validation of an ear tag-based accelerometer system for detecting grazing behavior of dairy cows.

The objective of the study was to develop a grazing algorithm for an ear tag-based accelerometer system (Smartbow GmbH, Weibern, Austria) and to validate the grazing algorithm with data from a noseband sensor. The ear tag has an acceleration sensor, a radio chip, and temperature sensor for calibration and it can monitor rumination and detect estrus and localization. To validate the ear tag, a noseband sensor (RumiWatch, Itin and Hoch GmbH, Liestal, Switzerland) was used. The noseband sensor detects pressure and acceleration patterns, and, with a software program specific to the noseband, pressure and acceleration patterns are used to classify data into eating, ruminating, drinking, and other activities. The study was conducted at the University of Minnesota West Central Research and Outreach Center (Morris, MN) and at Teagasc Animal and Grassland Research and Innovation Centre (Moorepark, Fermoy, Co. Cork, Ireland). During May and June 2017, observational data from Minnesota and Ireland were used to develop the grazing algorithm. During September 2018, data were collected by the ear tag and noseband sensor from 12 crossbred cows in Minnesota for a total of 248 h and from 9 Holstein-Friesian cows in Ireland for a total of 248 h. A 2-sided t-test was used to compare the percentage of grazing and nongrazing time recorded by the ear tag and the noseband sensor. Pearson correlations and concordance correlation coefficients (CCC) were used to evaluate associations between the ear tag and noseband sensor. The percentage of total grazing time recorded by the ear tag and by the noseband sensor was 37.0% [95% confidence interval (CI): 32.1 to 42.0] and 40.5% (95% CI: 35.5 to 45.6), respectively, in Minnesota, and 35.4% (95% CI: 30.6 to 40.2) and 36.9% (95% CI: 32.1 to 41.8), respectively, in Ireland. The ear tag and noseband sensor agreed strongly for monitoring grazing in Minnesota (r = 0.96; 95% CI: 0.94 to 0.97, CCC = 0.95) and in Ireland (r = 0.92; 95% CI: 0.90 to 0.94, CCC = 0.92). The results suggest that there is potential for the ear tag to be used on pasture-based dairy farms to support management decision-making.

An examination of the effects of labor efficiency on the profitability of grass-based, seasonal-calving dairy farms.

The seasonality of grass-based, seasonal-calving dairy systems results in disproportionately higher labor demands during the spring, when cows are calving, than in the remaining seasons. This study aimed to (1) examine the relationship between labor efficiency and profitability; (2) investigate strategies to reduce the hours worked per day by the farmer, family, and farm staff in the spring by having certain tasks outsourced; and (3) quantify the economic implications of those strategies. Data from an existing labor efficiency study on Irish dairy farms were used in conjunction with economic performance data from the farms. Tasks that required the highest level of farm labor per day in the spring were identified and hypothetical strategies to reduce the farm hours worked per day were examined. A stochastic budgetary simulation model was then used to examine the economic implications of employing these strategies and the effects of their use in conjunction with a proportionate increase in cow numbers that would leave the hours worked per day unchanged. The strategies were to use contractors to perform calf rearing, machinery work, or milking. Contracting out milking resulted in the greatest reduction in hours worked per day (5.6 h/d) followed by calf rearing (2.7 h/d) and machinery work (2 h/d). Reducing the hours worked per day by removing those tasks had slight (i.e., <5%) negative effects on profitability; however, maintaining the farm hours worked per day while utilizing the same strategies and increasing herd sizes resulted in profitable options. The most profitable scenario was for farms to increase herd size while contracting out milking.

Menstrual Suppression in Pediatric and Adolescent Patients with Disabilities Ranging from Developmental to Acquired Conditions: A Population Study in an Australian Quaternary Pediatric and Adolescent Gynecology Service from January 2005 to December 2015.

STUDY OBJECTIVE: The aim of this study was to review the efficacy of different medical modalities for menstrual suppression in the cohort of patients with disabilities who presented to the Queensland Paediatric and Adolescent Gynaecology (PAG) Service between January 2005 and December 2015. Menstrual suppression in adolescents with disabilities is an important aspect of care to support the patient and their carers in managing the complexities of menstrual hygiene, pain, and other discomfort associated with menses. It is important for general practitioners, pediatricians, and gynecologists to establish the right modality of suppression for each individual adolescent. DESIGN, SETTINGS, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: The study was a retrospective case notes review of 68 adolescents who presented to the Queensland PAG Service, Brisbane, Australia with a request for menstrual suppression. The medical interventions included treatment with either combined oral hormonal contraceptive, oral medroxyprogesterone, depot medroxyprogesterone, or the levonorgestrel intrauterine system (Mirena, Bayer). The primary outcome measure was success of menstrual suppression from commencement of medical intervention to achievement of complete amenorrhea or very light bleeding described as spotting, for each medical modality. Secondary outcomes were length of time from first treatment to first observed menstrual suppression, and the number of outpatient appointments taken to achieve menstrual suppression. RESULTS: Of the 68 adolescents, 59/68 (86.8%) successfully achieved menstrual suppression, with 9/68 (13.2%) having ongoing treatment or loss to follow-up at the time of conclusion of the study; 39/68 (57.4%) were menstrually suppressed with their chosen medical modality after their initial appointment. CONCLUSION: Medical modalities are highly effective in achieving menstrual suppression and no young women at this institution required a hysterectomy. Depot medroxyprogesterone was the most successful modality used to achieve menstrual suppression followed by the levonorgestrel intrauterine system. The combined oral hormonal contraceptive was the least successful medical treatment in achieving menstrual suppression.