Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants.

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10µm and <5µm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5µm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.

Genome-Wide Association Study of age at puberty and its (co)variances with fertility and stature in growing and lactating Holstein-Friesian dairy cattle.

Reproductive performance is a key determinant of cow longevity in a pasture-based, seasonal dairy system. Unfortunately, direct fertility phenotypes such as inter-calving interval or pregnancy rate tend to have low heritabilities and occur relatively late in an animal's life. In contrast, age at puberty (AGEP) is a moderately heritable, early-in-life trait, that may be estimated using an animal's age at first measured elevation in blood plasma progesterone (AGEP4) concentrations. Understanding the genetic architecture of AGEP4 in addition to genetic relationships between AGEP4 and fertility traits in lactating cows is important, as is its relationship with body size in the growing animal. Thus, the objectives of this research were 3-fold. First, to estimate the genetic and phenotypic (co)variances between AGEP4 and subsequent fertility during first and second lactations. Second, to quantify the associations between AGEP4 and height, length, and body weight (BW) measured when animals were around 11 mo old (SD = 0.5). Third, to identify genomic regions that are likely to be associated with variation in AGEP4. We measured AGEP4, height, length, and BW in around 5,000 Holstein-Friesian or Holstein-Friesian x Jersey crossbred yearling heifers, across 54 pasture-based herds managed in seasonal calving farm systems. We also obtained calving rate (CR42: success or failure to calve within the first 42 d of the seasonal calving period), breeding rate (PB21: success or failure to be presented for breeding within the first 21 d of the seasonal breeding period) and pregnancy rate (PR42: success or failure to become pregnant within the first 42 d of the seasonal breeding period) phenotypes from their first and second lactations. The animals were genotyped using the Weatherby's Versa 50K SNP array (Illumina, USA). The estimated heritabilities of AGEP4, height, length, and BW were 0.34 (0.30, 0.37), 0.28 (0.25, 0.31), 0.21 (0.18, 0.23), and 0.33 (0.30, 0.36), respectively. In contrast, the heritabilities of CR42, PB21 and PR42 were all < 0.05 in both first and second lactations. The genetic correlations between AGEP4 and these fertility traits were generally moderate ranging from 0.11 to 0.60, whereas genetic correlations between AGEP4 and yearling body conformation traits ranged from 0.02 to 0.28. Our genome wide association study (GWAS) highlighted a genomic window on chromosome 5 that was strongly associated with variation in AGEP4. We also identified 4 regions, located on chromosomes 14, 6, 1 and 11 (in order of decreasing importance), that exhibited suggestive associations with AGEP4. Our results show that AGEP4 is a reasonable predictor of estimated breeding values (EBVs) for fertility traits in lactating cows. While the GWAS provided insights into genetic mechanisms underpinning AGEP4, further work is required to test genomic predictions of fertility that use this information.

Coronary intravascular lithotripsy and rotational atherectomy for severely calcified stenosis: Results from the ROTA.shock trial.

BACKGROUND: Severely calcified coronary lesions present a particular challenge for percutaneous coronary intervention. AIMS: The aim of this randomized study was to determine whether coronary intravascular lithotripsy (IVL) is non-inferior to rotational atherectomy (RA) regarding minimal stent area (MSA). METHODS: The randomized, prospective non-inferiority ROTA.shock trial enrolled 70 patients between July 2019 and November 2021. Patients were randomly (1:1) assigned to undergo either IVL or RA before percutaneous coronary intervention of severely calcified coronary lesions. Optical coherence tomography was performed at the end of the procedure for primary endpoint analysis. RESULTS: The primary endpoint MSA was lower but non-inferior after IVL (mean: 6.10 mm2 , 95% confidence interval [95% CI]: 5.32-6.87 mm2 ) versus RA (6.60 mm2 , 95% CI: 5.66-7.54 mm2 ; difference in MSA: -0.50 mm2 , 95% CI: -1.52-0.52 mm2 ; non-inferiority margin: -1.60 mm2 ). Stent expansion was similar (RA: 0.83 ± 0.10 vs. IVL: 0.82 ± 0.11; p = 0.79). There were no significant differences regarding contrast media consumption (RA: 183.1 ± 68.8 vs. IVL: 163.3 ± 55.0 mL; p = 0.47), radiation dose (RA: 7269 ± 11288 vs. IVL: 5010 ± 4140 cGy cm2 ; p = 0.68), and procedure time (RA: 79.5 ± 34.5 vs. IVL: 66.0 ± 19.4 min; p = 0.18). CONCLUSION: IVL is non-inferior regarding MSA and results in a similar stent expansion in a random comparison with RA. Procedure time, contrast volume, and dose-area product do not differ significantly.

Genome-wide association study of anogenital distance and its (co)variances with fertility in growing and lactating Holstein-Friesian dairy cattle.

Anogenital distance (AGD) is a moderately heritable trait that can be measured at a young age that may provide an opportunity to indirectly select for improved fertility in dairy cattle. In this study, we characterized AGD and its genetic and phenotypic relationships with a range of body stature and fertility traits. We measured AGD, shoulder height, body length, and body weight in a population of 5,010 Holstein-Friesian and Holstein-Friesian × Jersey crossbred heifers at approximately 11 mo of age (AGD1). These animals were born in 2018 across 54 seasonal calving, pasture-based dairy herds. A second measure of AGD was collected in a subset of herds (n = 17; 1,956 animals) when the animals averaged 29 mo of age (AGD2). Fertility measures included age at puberty (AGEP), then time of calving, breeding, and pregnancy during the first and second lactations. We constructed binary traits reflecting the animal's ability to calve during the first 42 d of their herd's seasonal calving period (CR42), be presented for breeding during the first 21 d of the seasonal breeding period (PB21) and become pregnant during the first 42 d of the seasonal breeding period (PR42). The posterior mean of sampled heritabilities for AGD1 was 0.23, with 90% of samples falling within a credibility interval (90% CRI) of 0.20 to 0.26, whereas the heritability of AGD2 was 0.29 (90% CRI 0.24 to 0.34). The relationship between AGD1 and AGD2 was highly positive, with a genetic correlation of 0.89 (90% CRI 0.82 to 0.94). Using a GWAS analysis of 2,460 genomic windows based on 50k genotype data, we detected a region on chromosome 20 that was highly associated with variation in AGD1, and a second region on chromosome 13 that was moderately associated with variation in AGD1. We did not detect any genomic regions associated with AGD2 which was measured in fewer animals. The genetic correlation between AGD1 and AGEP was 0.10 (90% CRI 0.00 to 0.19), whereas the genetic correlation between AGD2 and AGEP was 0.30 (90% CRI 0.15 to 0.44). The timing of calving, breeding, and pregnancy (CR42, PB21, and PR42) during first or second lactations exhibited moderate genetic relationships with AGD1 (0.19 to 0.52) and AGD2 (0.46 to 0.63). Genetic correlations between AGD and body stature traits were weak (≤0.16). We conclude that AGD is a moderately heritable trait, which may have value as an early-in-life genetic predictor for reproductive success during lactation.

An online survey to understand the needs of caregivers of family members with 22q11 deletion syndrome.

BACKGROUND: Most individuals with 22q11.2 deletion syndrome (22q11DS) have multi-system and lifelong needs requiring substantial support. Their primary caregivers are usually family members who dedicate lifelong time and effort to their role. The pressures of their roles can negatively impact caregivers' psychosocial well-being, suggesting a need for additional support for this community who currently have no specialised interventions available. METHOD: This online study surveyed 103 caregivers of family members with 22q11DS to determine the barriers to accessing support that they faced, the kind of support they would value and whether an online intervention could meet their needs. RESULTS: The caregivers indicated that a brief online intervention focused on teaching practical skills and connecting them with a peer network of support would be most valuable. CONCLUSIONS: Future studies are planned that will build on these results by designing and testing online interventions tailored to this community.

Animal- and herd-level factors associated with onset of puberty in grazing dairy heifers.

AIMS: To explore animal- and herd-level risk factors influencing age at puberty in predominantly Holstein-Friesian dairy heifers managed in seasonal, pasture-based systems. METHODS: Heifers born in spring 2018 (n = 5,010) from 54 commercial dairy herds in New Zealand were visited on three occasions when the mean heifer age, within herd, was 10 (visit 1; V1), 11 (V2) and 12 (V3) months old. Blood samples were collected on each visit and liveweight, stature and anogenital distance (AGD) were measured at V2. Heifers were defined as having reached puberty at the first visit where blood progesterone was elevated (≥ 1 ng/mL). Animal-level response variables included pubertal status by V1, V2 and V3, and age at puberty (or age at V3 plus 31 days for those that had not attained puberty by V3). To explore herd-level management factors, farmers answered a questionnaire relating to animal location, land type, health, feeding, and management between weaning and mating. A partial least squares regression was undertaken to identify herd-level factors associated with the greatest influence on puberty rate within herd. RESULTS: The mean age at puberty was 352 (SD 34.9) days. Heavier animals at a greater proportion of expected mature liveweight based on their breeding value for liveweight, or animals with a higher breed proportion of Jersey and lower breed proportion of Holstein, were associated with earlier puberty. Herd puberty rates varied widely among enrolled herds, and averaged 20%, 39% and 56% by V1, V2 and V3, respectively. Liveweight, followed by breed and land type, had the greatest influence on the herd puberty rate. Heifer herds with a greater mean liveweight (absolute and proportion of expected mature weight) or greater Jersey proportion had more animals that reached puberty at any visit, whereas herds located on steep land or with greater Holstein breed proportions had lower puberty rates. Management-related factors such as vaccinations, provision of feed supplements, and weighing frequency were also herd-level risk factors of puberty but had less influence. CONCLUSIONS AND CLINICAL RELEVANCE: This study highlights the importance of having well-grown heifers for increasing the chances of earlier puberty onset and the effect of breed and youngstock management to achieve growth targets. These outcomes have important implications for the optimal management of heifers to achieve puberty before their maiden breeding and for the timing of measurements to potentially incorporate a puberty trait in genetic evaluations.

Variance parameter estimation for age at puberty phenotypes under 2 levels of phenotype censorship.

Age at puberty (AGEP) is a moderately heritable trait in cattle that may be predictive of an animal's genetic merit for reproductive success later in life. In addition, under some mating strategies (for example, where mating begins before all animals have attained puberty) animals that attain puberty at a relatively young age will also likely conceive earlier than their herd mates, and thus begin their productive life earlier. Unfortunately, AGEP is challenging to measure because animals must be observed over a period of several months. Our objectives for this study were twofold. The first objective was to produce variance components for AGEP. The second objective was to investigate the implications of a simplified phenotyping strategy for AGEP, when the interval between repeated blood plasma progesterone measures was extended from weekly to monthly, increasing the extent of left, interval, and right censoring. We measured AGEP in a closely monitored population of around 500 Holstein-Friesian heifers, born in 2015 and managed under a seasonal, pasture-based dairy system. Animals were blood tested weekly from approximately 240 to 440 d of age and were deemed to have reached puberty when blood plasma progesterone elevation (>1 ng/mL) was detected in 2 of 3 consecutive blood tests (AGEP_Weekly). To simulate a simplified phenotyping strategy based on monthly herd visits (AGEP_Monthly), we selectively disregarded data from all but 3 blood test events, when animals were around 300, 330, and 360 d of age (standard deviation = 14.5 d). The posterior mean of estimated heritabilities for AGEP_Weekly was 0.54, with a 90% credibility interval (90% CRI) of 0.41 to 0.66, whereas it was 0.44 (90% CRI 0.32 to 0.57) for AGEP_Monthly. The correlation between EBVs for AGEP_Weekly and AGEP_Monthly was 0.87 (90% CRI, 0.84 to 0.89). We conclude that in this population, AGEP is a moderately heritable trait. Further, increasing phenotype censorship from weekly to monthly observations would not have altered the main conclusions of this analysis. Our results support the strategic use of censoring to reduce costs and animal ethics considerations associated with collection of puberty phenotypes.

The first week following insemination is the period of major pregnancy failure in pasture-grazed dairy cows.

A 60% pregnancy success for inseminations is targeted to optimize production efficiency for dairy cows within a seasonal, pasture-grazed system. Routine measures of pregnancy success are widely available but are limited, in practice, to a gestation stage beyond the first 28 d. Although some historical data exist on embryonic mortality before this stage, productivity of dairy systems and genetics of the cows have advanced significantly in recent decades. Accordingly, the aim was to construct an updated estimate of pregnancy success at key developmental stages during the first 70 d after insemination. Blood samples were collected for progesterone concentrations on d 0 and 7. A temporal series of 4 groups spanning fertilization through d 70 were conducted on 4 seasonal, pasture-grazed dairy farms (n = 1,467 cows) during the first 21 d of the seasonal breeding period. Morphological examination was undertaken on embryos collected on d 7 (group E7) and 15 (group E15), and pregnancy was diagnosed via ultrasonography on approximately d 28 and 35 (group E35) as well as d 70 (group E70). Fertilization, embryo, and fetal evaluation for viability established a pregnancy success pattern. Additionally, cow and on-farm risk factor variables associated with pregnancy success were evaluated. We estimated pregnancy success rates of 70.9%, 59.1%, 63.8%, 62.3%, and 56.7% at d 7, 15, 28, 35, and 70, respectively. Fertilization failure (15.8%) and embryonic arrest before the morula stage (10.3%) were the major developmental events contributing to first-week pregnancy failures. Embryo elongation failure of 7% contributed to pregnancy failure during the second week. The risk factors for pregnancy success that were related to the cows included interval between calving and insemination, and d-7 plasma progesterone concentrations, whereas insemination sire was associated with pregnancy outcome. Most pregnancy failure occurs during the first week among seasonal-calving pasture-grazed dairy cows.

Adaptive immune response ranking is associated with reproductive phenotypes in grazing dairy cows divergent in genetic merit for fertility traits.

A strong adaptive immune response has been reported to have positive effects on fertility; therefore, we investigated antibody- and cell-mediated adaptive immune responses (AMIR and CMIR, respectively) and their associations with reproductive phenotypes using a population of animals that differed in their estimated genetic merit for fertility traits (fertility breeding value; FertBV). Holstein-Friesian heifers (n = 528) grazed on pasture in 4 herds based on age. These herds included 277 heifers of positive (POS) FertBV and 251 of negative (NEG) FertBV. The adaptive immune response (IR) was evaluated before puberty at 7.5 mo of age and used to rank animals as high, average, or low for AMIR, CMIR, and overall IR (combined CMIR and AMIR). The animals were studied from 12 wk of age through to the end of their second lactation to measure growth, puberty, and timing and success of fertility phenotypes, including those related to ovulation and pregnancy. Initial analysis indicated no difference in fertility outcomes between cows ranked as high or average for AMIR (n = 55, n = 407, respectively), CMIR (n = 87, n = 354, respectively), and IR (n = 29, n = 470, respectively), so these groups were pooled as HiAv-IR. Proportions of heifers of POS FertBV were similar within HiAv and low categories across AMIR (0.52 and 0.58, respectively), CMIR (0.51 and 0.59, respectively), and IR (0.53 and 0.48, respectively). Heifers with HiAv-IR had a greater average daily weight gain from 13 to 52 wk of age (661 g, 95% confidence interval 652, 669 vs. 619 g, 95% confidence interval 591, 647) and tended to be younger at puberty (371 d, 95% confidence interval 366, 377 vs. 385 d, 95% confidence interval 369, 401) than low-IR heifers. Low-CMIR cows of a NEG FertBV had a >40 d longer calving to first ovulation interval during their first lactation compared with HiAv-CMIR NEG FertBV cows. Low-CMIR cows also had decreased pregnancy rates at both 3 wk (25% ± 7% vs. 42% ± 3%; least squares means ± standard error) and 6 wk (33% ± 7% vs. 54% ± 3%; least squares means ± standard error) into the seasonal breeding period during their first lactation, compared with HiAv-CMIR cows. In summary, although the number of POS and NEG FertBV cows was similar in each immune group; interaction effects between FertBV and immune ranking on reproductive phenotypes are evident when cows were ranked by the overall IR. There were also associations between dairy cows' CMIR ranking and ability to return to estrus and become pregnant early in the breeding period, which will have benefits in seasonal breeding systems.

Relationships between prostaglandin concentrations, a single nucleotide polymorphism in HSD17B12, and reproductive performance in dairy cows.

Prostaglandins are involved in multiple processes important for fertility, with previous work in mice highlighting a potential role for the HSD17B12 gene in prostaglandin biosynthesis. This study aimed to determine the associations among circulating prostaglandin concentrations, a missense SNP in the HSD17B12 gene predicted to disrupt protein function, and fertility traits in first-lactation Holstein-Friesian dairy cows. We used a study population of approximately 500 animals specifically bred to have either a positive (POS, +5%) or negative (NEG, -5%) genetic merit for fertility (FertBV). Genotypes of a previously identified SNP (rs109711583) in HSD17B12 were determined, with 116 animals genotyped as AA, 215 genotyped as AG, and 153 genotyped as GG. Plasma concentrations of prostaglandin E2 and the PGF2α metabolite PGFM were determined at 3 time points (12 mo of age, 4 d postpartum, and 5 wk postpartum during first lactation) in a selection of animals with AA and GG genotypes from both the POS and NEG FertBV groups (n = 33-40 in each genotype for each FertBV group). Binary reproductive traits (yes or no) examined included submission for artificial breeding in the first 3 or 6 wk of the seasonal breeding period; conception to first service; conception during the first 6 wk of the breeding period; and pregnant at the end of the breeding period. Uterine health at 6 wk after calving was examined by evaluating the percentage of polymorphonuclear leukocytes following uterine cytology and by scoring vaginal discharge based on the presence of purulent material. The 3-wk submission rate was increased in animals that carried the G allele of the missense SNP in HSD17B12, but no differences were present among genotypes for 6-wk submission rate. The trait was additive, with each increase of the G allele increasing the 3-wk submission rate by 6 to 7%. We did not observe any consistent associations between SNP alleles and circulating PGE2 concentrations; however, a complex 3-way interaction among time, fertility group, and SNP allele was present for PGFM concentrations. Plasma concentrations of PGE2 were increased approximately 40% at 5 wk postpartum in animals that were submitted for breeding within 3 or 6 wk of the start of the breeding season, and in those that conceived during the first 6 wk of breeding, compared with those that did not. Plasma concentrations of PGFM were decreased approximately 20% in those animals that conceived to their first service and tended to be decreased in animals that were pregnant at the end of the breeding period, compared with those that were not. In summary, associations were observed between the SNP in HSD17B12 and submission rate by d 21 of the breeding season, as well as between circulating prostaglandin concentrations and fertility traits, but the SNP was not consistently linked to changes in prostaglandin concentrations. Thus, the association between submission rate by d 21 of the breeding season and the SNP in HSD17B12 were unlikely driven by changes in prostaglandins.

Response to kisspeptin and gonadotropin-releasing hormone agonist administration in Holstein-Friesian dairy heifers with positive or negative genetic merit for fertility traits.

Previous research has identified that Holstein-Friesian dairy heifers with positive (POS) genetic merit for fertility traits (FertBV) reach puberty earlier than heifers with negative (NEG) FertBV. The hypothalamus-pituitary-gonadal (HPG) axis is functional in heifers before the onset of puberty, with increased LH release evident as heifers progress toward puberty. We investigated the functionality of the HPG axis in peripubertal Holstein-Friesian dairy heifers with divergent POS or NEG FertBV, hypothesizing that the earlier puberty onset of POS heifers is associated with earlier activation of the HPG axis than in NEG heifers. In experiment 1, we tested the dose responsiveness of POS heifers to an intravenous injection of either kisspeptin [Kiss; 2, 4, or 8 µg/kg of body weight (BW); n = 3 per dose] or a GnRH agonist (buserelin; 5, 10, or 20 ng/kg of BW; n = 3 per dose). The use of these 2 agonists investigates the status of the HPG axis in both the hypothalamus (Kiss) and pituitary (buserelin) glands. Doses of 4 µg/kg BW of Kiss and 10 ng/kg BW of buserelin produced submaximal LH responses and were used in experiment 2, in which previously unused POS (n = 22) and NEG (n = 18) FertBV heifers were challenged with both agonists at 10 and 12 mo of age in a partial crossover design. Heifers were randomly allocated to treatment groups, balanced for age and BW. The LH response to buserelin was greater in POS heifers than NEG heifers at 10 mo of age, with no difference in response at 12 mo. The FSH response to buserelin and the LH and FSH responses to Kiss did not differ between the POS and NEG heifers at either age. These results indicate an association between divergent genetic merit for fertility and the LH release to buserelin at 10 mo of age, supporting the hypothesis that gonadotropin responsiveness to a GnRH agonist is more advanced in POS heifers than in NEG heifers.

The microenvironment of ovarian follicles in fertile dairy cows is associated with high oocyte quality.

We hypothesised that heifers and cows with positive genetic merit for fertility would have a follicular microenvironment that resulted in better quality oocytes. To test this, we compared cumulus cell-oocyte complexes (COC) and follicular fluid from preovulatory follicles of 36 Holstein-Friesian nulliparous heifers and 50 primiparous lactating cows with either positive (POS, +5%) or negative (NEG, -5%) fertility breeding values (FertBV). Established gene markers of oocyte quality were measured in individual cumulus cell masses and oocytes, and concentrations of amino acids, steroids, and metabolites were quantified in corresponding follicular fluid and plasma. The timing of visually detectable oestrus in NEG FertBV heifers was inconsistent with their stage of COC maturation. Retrospective analyses of oestrous activity data indicated that NEG FertBV heifers were sampled earlier. Their recovered COC were morphologically less mature and exhibited differential expression of genes that are associated with follicular maturation (lower levels of BMPR2) and protein processing (higher levels of HSP90B1). Despite consistent sampling times being achieved in the lactating cows, lower concentrations of serine, proline, methionine, isoleucine, and non-esterified fatty acids were present in follicular fluid from POS FertBV cows. This was associated with higher expression of gene biomarkers of good oocyte quality (VCAN, PDE8A) in COC recovered from POS FertBV cows. This study supports our hypothesis that the follicular microenvironment in lactating dairy cows with high genetic merit leads to COC with higher metabolic rates and oocytes of superior quality. Moreover, an additional stressor such as lactation is required for this difference to be pronounced.

Changes in plasma electrolytes, minerals, and hepatic markers of health across the transition period in dairy cows divergent in genetic merit for fertility traits and postpartum anovulatory intervals.

Peripartum metabolism and subsequent reproductive performance of dairy cows are linked, with maladaptation over the transition period associated with poor reproductive success. A herd of seasonal calving, grazing dairy cows was established that differed in their genetic merit for fertility traits. The heifers were produced by a customized mating program to achieve a 10-percentage point divergence in the New Zealand fertility breeding value (FertBV) as follows: +5 FertBV (POS) versus -5% FertBV (NEG), while also limiting divergence in other breeding values, including body weight, body condition score, and milk production. In this study, we aimed to characterize differences in metabolic, mineral, and metabolic stress marker profiles during their first postpartum transition period as primiparous heifers and to examine if animals with longer postpartum anestrous intervals (PPAI; more than 66 d compared with less than 35 d) had greater metabolic dysfunction. Blood was sampled at -21, -14, -7, 0, 4, 7, 10, 14, 17, 21, 28, and 35 d relative to calving in 455 primiparous cows and plasma analyzed. The NEG cows had lower concentrations of both plasma nonesterified fatty acids and ß-hydroxybutyrate at d 7 compared with POS cows. Detailed temporal profiling of various metabolic, mineral, and metabolic stress markers was undertaken in a subset of cows (n = 70). Cows were selected retrospectively to create 4 groups in a 2 × 2 factorial design with either a POS or NEG FertBV and either a short (19-35 d) or long (66-131 d) PPAI. The NEG cows tended, on average, to have lower nonesterified fatty acids and ß-hydroxybutyrate concentrations compared with POS cows across the transition period. Mean body weight and body condition score was greatest in NEG cows when compared with the POS cows and an interaction with day demonstrated this only occurred precalving. They also had indications of improved liver health precalving, with higher albumin-to-globulin ratios and lower bilirubin concentrations. Concentrations of aspartate aminotransferase were lower, and the Na-to-Cl ratio was greater in cows with a long versus a short PPAI at d 28 and d 35 after calving, potentially because of cows with a short PPAI (19-35 d) returning to estrous during this time. Magnesium concentrations were lower in NEG cows with a short PPAI from d 21 onwards, indicating NEG cows may metabolically respond to estrous differently than POS cows. The NEG-long PPAI cows had greater gamma-glutamyl transferase concentrations from calving until d 28 and lower bilirubin concentrations throughout the transition period. Together, the results demonstrate significant effects of FertBV on peripartum metabolic status. However, most of the markers tested returned to reference intervals within 4 d after calving or remained within those intervals for the whole transition period, indicating relatively minor biological effects of FertBV on transition period adaptation. The profound differences in reproductive performance among the groups was not explained by underlying differences in metabolic responses during the transition period.

Estrous activity in lactating cows with divergent genetic merit for fertility traits.

This observational study aimed to determine the effect of genetic merit for fertility traits on estrous expression and estrous cycle duration in grazing dairy cows, as measured by an activity monitoring device. A secondary aim was to describe changes in expression of estrus that occur during successive estrous cycles postpartum. Neck-mounted, activity-monitoring devices (Heatime, SCR Engineers Ltd.) were fitted to nulliparous Holstein-Friesian heifers with positive (POS FertBV) or negative genetic merit for fertility traits (NEG FertBV) to capture activity data during their first and second lactations (POS FertBV: n = 242, n = 188; NEG FertBV: n = 159, n = 87 in lactation 1 and 2, respectively). An estrous event was identified when the activity change index exceeded 26 activity units (AU) for 4 h. A total of 1,254 and 892 estrous events were identified in lactation 1 and 2, respectively. Estrous duration was defined as the interval between when the threshold was first exceeded and when activity dropped below the threshold, with no new event starting within 24 h of the end of the previous event. This definition of estrus included cows in which activity crossed the threshold multiple times in a day and were classified as a single estrous event. A second measure, high activity duration, was defined as the total hours that activity exceeded the threshold. To characterize estrous activity, peak activity (above baseline) and total activity (area under the curve of activity above baseline) were measured. Compared with NEG FertBV cows, POS FertBV cows had more active, longer estrous events. In lactation 1, the POS FertBV group had a mean estrous duration and a high activity duration of 12.5 and 12.4 h compared with 11.4 and 11.3 h for the NEG FertBV group [standard error of the difference (SED) = 0.5 and 0.4 h, respectively]. This significant difference also occurred in lactation 2, with a mean estrous duration of 13.1 versus 11.8 h (SED = 0.5 h) and a high activity duration of 13.0 versus 11.8 h (SED = 0.4 h) in the POS and NEG FertBV groups, respectively. Total activity and peak activity were greater in the POS compared with the NEG FertBV group in lactation 1 (peak activity: 65.5 vs. 55.8 AU, SED = 2.4 AU; total activity: 588 vs. 494 AU, SED = 25 AU) and lactation 2 (peak activity: 72.5 vs. 61.2 AU, SED = 2.9 AU; total activity: 648 vs. 541 AU, SED = 30 AU). Estrous cycle duration did not differ between the POS and NEG FertBV groups (lactation 1: 20.4 vs. 20.6 d, SED = 0.25; lactation 2: 20.8 vs. 21.0 d, SED = 0.28). Less estrous activity of the cow was associated with the first postpartum estrus. In contrast, the number of previous estrous events did not consistently affect the duration of the subsequent estrous cycle. The outcomes of this study provide evidence that positive genetic merit for fertility traits is associated with more overt estrous expression. Selection for these traits may improve estrous expression and thus estrous detection in commercial herds.

Investigating anogenital distance and antral follicle count as novel markers of fertility within a herd of cows with positive or negative genetic merit for fertility traits.

Using early-in-life markers of reproductive characteristics may enhance the speed and success of genetic improvement in fertility. We investigated 2 phenotypes that can be measured early in life and are moderately heritable to determine their association with traditional measures of reproductive success and genetic variation under a seasonal-calving, pasture-based system. Cows were bred to be divergent in the New Zealand Fertility Breeding Value, which estimates genetic merit for fertility. Cows consisted of 2 groups with an average positive (+5%) or negative (-5%) genetic merit for fertility traits and were expected to have large diversity in reproductive outcomes. Calves were genotyped at 41 ± 3.1 d of age (mean ± SD; n = 538), and antral follicle counts (AFC) were measured when they were postpubertal heifers before their first breeding (416 ± 15 d old; 92-d range; n = 520). The anogenital distance (AGD) was measured in 478 primiparous cows of this same population 50 to 60 d after the breeding start date when they were 881 ± 25 d old (145-d range). The AGD was shorter in animals with a positive genetic merit for fertility traits (based on parent averages). An indicator of herd reproductive success in a seasonal-calving system (recalving by 6 wk in lactation 2) was chosen for logistic regression with cross-validation, and if significant, a cut-off was calculated that categorized animals into groups. Both linear and quadratic regression was undertaken, and the model with the greatest sensitivity for detection of nonpregnant cows used. The AGD linear model was significant with a sensitivity of 64% and a specificity of 48%. This model resulted in a cut-off of 102 mm, which we used to classify cows as short (≤102 mm) or long (>102 mm) AGD animals. Primiparous cows with a short AGD were more likely to be pregnant within the first 3 and 6 wk of mating, and become pregnant as a primiparous cow, than those with a long AGD. The time from calving to conception was 20 d earlier in short AGD compared with long-AGD cows. None of the models tested for AFC were significant; therefore cows were categorized into 3 groups based on previous work in seasonal systems. However, associations between fertility phenotypes and AFC group were limited. Genomic regions of interest for AGD and AFC did not overlap, indicating phenotypes were genetically independent. Overall, AGD appears as a promising early marker of fertility in seasonal grazing systems.

Positive genetic merit for fertility traits is associated with superior reproductive performance in pasture-based dairy cows with seasonal calving.

New Zealand's Fertility Breeding Value (FertBV) is reported as the percentage of a sire's daughters that calve in the first 42 d of the seasonal calving period and is an estimate of genetic merit for fertility for dairy cattle. Reproductive physiology, milk production, and changes in body weight and body condition score of 2 groups of cows divergent in FertBV (+5.0%: POS; -5.1%: NEG) were characterized during their first 2 lactations. Cows grazed fresh pasture and were managed in a seasonal calving system; they were bred by artificial insemination on observed estrus for the entire breeding period (98 d in lactation 1 and 76 d in lactation 2). During lactation 1, all animals were primiparous and were randomly allocated to 1 of 2 herds, ensuring each herd was balanced for FertBV and expected calving date. During lactation 2, cows that became pregnant during lactation 1 were managed as 1 herd. Cows not inseminated in the first 42 d of the breeding season were examined for the presence of a corpus luteum and treated with an anestrus program. On average, the interval from calving to ovulation was 19 d longer in lactation 1 and 10 d longer in lactation 2 for NEG FertBV cows. The percent of cows submitted for artificial insemination after 21 d (i.e., submission rate) was 38 and 25 percentage points greater in the POS FertBV cows during lactations 1 and 2, respectively. Pregnancy rate from 42 d of breeding was 33 and 30 percentage points greater, respectively. There was no effect of FertBV on vaginal discharge score postcalving; however, POS FertBV cows had a 50% lower risk of having subclinical endometritis (polymorphonuclear leukocytes >7%) 42 d postcalving. Interactions between FertBV and month relative to calving identified that NEG FertBV cows were fatter (greater body condition score) in the month before calving, but thinner between 3 and 5 mo postcalving. There was no effect of FertBV on lactation length, estimated 270-d milk yields, or daily milk, fat, or protein yields, and only small effects on milk fat and protein percentage across the lactations. In summary, the POS FertBV cows had superior uterine health, a shorter calving to ovulation interval, a greater submission rate, and a greater pregnancy rate earlier in the breeding season when compared with the NEG FertBV cohort. Based on these results, these may be useful phenotypes to include in genetic selection indices.

[Palliative care in patients with left ventricular assist devices: systematic review]. / "Palliative care" bei Patienten mit Linksherzunterstützungssystem: systematische Übersichtsarbeit.

BACKGROUND: An increasing number of patients reach the final stage of heart failure with heart transplantation as the only curative treatment. Mechanical circulatory support, such as left ventricular assist devices (LVAD) are becoming increasingly more important at this stage of the disease. An LVAD improves the quality of life and prolongs the lifespan. The LVAD is used as a bridge to transplantation (BTT) for patients waiting for a donor heart or as a destination therapy (DT) with no transplantation intended; nevertheless, implantation is often associated with complications and the prognosis remains unfavorable in DT cases or after transition from BTT to DT. For patients the device may be a source of physical and psychological distress and can become a burden for families and caregivers. So far it remains unclear whether LVAD treatment is an indication for concurrent palliative care. OBJECTIVE: The aim of this study was to collect the current data on the influence of palliative care in LVAD patients and to identify possible formats of palliative care in clinical practice. MATERIAL AND METHODS: In May 2020, a systematic literature search was performed using the PICOS instrument in six different databases, i.e. PubMed, Cochrane library, Google scholar, Scopus, Web of Science and Journals@Ovid. We included quantitative and qualitative studies in English and German. Case reports, comments and pediatric studies were excluded. RESULTS: A total of 21 publications from an initial number of 491 were included in this review. The integration of palliative care in the context of LVAD implantation increased the number of advance directives and documented surrogate decision makers. Studies found a positive influence of palliative care on the conditions and place of death, family involvement and symptom and pain management. Involvement in the decision-making process may improve patient selection for LVAD treatment and helps patients to make the decision on informed consent. Various formats for the integration of palliative medical concepts into LVAD treatment are reported. It is not clear when palliative care involvement should start; however, most articles support an early and continuous integration in the LVAD process. We have aggregated possible topics for palliative care consultations from a number of publications. Mutual teaching of both LVAD and palliative care teams is recommended. Integration of a dedicated LVAD palliative care specialist as part of the LVAD team can support care for patients as well as clinicians. CONCLUSION: The role of palliative care in LVAD patients in clinical practice in the German-speaking area is not standardized. Early and continuous integration of palliative care into the course of LVAD treatment can improve the quality of care. Benefits for LVAD patients, caregivers and clinicians are described. For this purpose, recommendations as well as professional training for palliative care practitioners are useful. Further studies are needed to clarify the impact of palliative care in both DT and BTT patients.

[General palliative care during the pandemic]. / Allgemeine Palliativversorgung in Pandemiezeiten.

BACKGROUND: The German healthcare system is facing unprecedented challenges due to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Palliative care for critically ill patients and their families was also severely compromised, especially during the first wave of the pandemic, in both inpatient and outpatient settings. MATERIALS AND METHODS: The paper is based on our experience in routine inpatient palliative care and partial results of a study conducted as part of the collaborative project "National Strategy for Palliative Care in Pandemic Times (PallPan)". Based on our experience from the inpatient care of patients suffering from severe or life-limiting disease, best-practice examples for improving or maintaining care in the on-going pandemic are described. RESULTS: Restrictive visitor regulations, communication barriers and insufficient possibilities to accompany dying patients or their grieving relatives continue to pose major challenges in general and specialized inpatient palliative care. In order to maintain high-quality palliative care, it is necessary to create structures that enable targeted therapy discussions and end-of-life care in the presence of relatives. Therefore, innovative communication methods like video calls or individualized exceptions from visitor restrictions are needed. CONCLUSIONS: Adequate care for seriously ill and dying patients and their relatives must be guaranteed during the pandemic. Individual arrangements should be arranged and implemented. If available, earlier involvement of specialized palliative care teams can be beneficial.

Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: A systematic comparison.

For the two proteins myoglobin and fluoroacetate dehalogenase, we present a systematic comparison of crystallographic diffraction data collected by serial femtosecond (SFX) and serial synchrotron crystallography (SSX). To maximize comparability, we used the same batch of micron-sized crystals, the same sample delivery device, and the same data analysis software. Overall figures of merit indicate that the data of both radiation sources are of equivalent quality. For both proteins, reasonable data statistics can be obtained with approximately 5000 room-temperature diffraction images irrespective of the radiation source. The direct comparability of SSX and SFX data indicates that the quality of diffraction data obtained from these samples is linked to the properties of the crystals rather than to the radiation source. Therefore, for other systems with similar properties, time-resolved experiments can be conducted at the radiation source that best matches the desired time resolution.