Thermochemistry of Species in Gas-Phase Thermal Oxidation of C2 to C8 Perfluorinated Carboxylic Acids.

New thermochemical properties, Cp°(T), H°(T), S°(T), and G°(T), are predicted for 123 species involved in the thermal destruction of perfluorinated carboxylic acids (PFCAs) using computational quantum chemistry and ideal-gas statistical mechanics. Relevant species were identified from the development of mechanisms for the pyrolysis and oxidation of PFCAs of C2 to C8 in length. Partition functions were obtained from the results of calculations at the G4 level for species up to C4 in length and M06-2X-D3(0)/def2-QZVPP for species C5 to C8 in length. The 1D hindered-rotor approximation was used to correct for torsional modes in the larger species. Ideal-gas thermochemistry was computed and fitted to 7-parameter NASA polynomials over a 200-2500 K temperature range, and the data are provided in standardized format. To gauge the effects of both method and basis set choice, enthalpies of formation at 0 K are calculated from various other density functionals (including B3LYP and ωB97XD), basis sets, and composite model chemistries (CBS-QB3). They are benchmarked against data from the Active Thermochemical Tables, high-level ANL0 calculations from the literature, and G4 calculations from this work. The effects of internal rotations and other anharmonicities are discussed, and bond dissociation energies and reaction equilibria provide mechanistic insights.

Influence of gastric residual assessment in preterm neonates on time to achieve enteral feeding (the GRASS trial)-Multi-centre, assessor-blinded randomised clinical trial.

PURPOSE: Gastric residual measurement is routinely performed in premature infants prior to feeding despite a lack of evidence of benefit. We aimed to evaluate if the exclusion of routine gastric residual measurement and evaluation has an impact on the time taken to achieve full enteral feeding in preterm neonates. METHODS: International multi-centre randomised controlled trial. Clinically stable, appropriate for gestational age infants between 26+0 and 30+6 weeks of gestation and less than 1.5 kg birth weight were eligible. Infants were randomised to the intervention arm (no monitoring of gastric aspirates) or control arm (routine care). Primary outcome was the achievement of enteral feeds of 100 ml/kg/day by day 5 of life. RESULTS: Ninety-five infants were recruited with 88 included in an intention-to-treat analysis, 45 in the intervention arm and 43 in the control arm. There was no imbalance in baseline characteristics. Thirty-three (73.3%) infants in the intervention group and 32 infants (74.4%) in the control group reached full feeds by day 5 of life (p = 0.91) with no difference in median time to full feeds. There were no statistically significant differences in survival or the major morbidities of prematurity. CONCLUSION:  There was no difference in time to attainment of enteral feeds of 100 ml/kg/day in premature infants when gastric residuals were not monitored. In the absence of a clinical benefit to routine monitoring, it may be appropriate to discontinue this practice and only monitor residuals when clinical concern of feeding intolerance or gastrointestinal pathology arises in this group of patients. TRIAL REGISTRATION:  NCT03111329- https://clinicaltrials.gov/ . Registered 06/04/2017. WHAT IS KNOWN: • Previous randomized trials have shown little benefit to the performance of routine assessment of gastric residuals in preterm infants. Despite this, they continue to be performed due to concerns from observational data regarding development of NEC. Meta-analysis to date has failed to answer the question regarding NEC. WHAT IS NEW: • In very low birth weight infants who are fed using modern feeding practice of faster feed advancement, to minimize use of central access and parenteral nutrition, exclusion of routine checks of gastric residuals did not increase the proportion of infants reaching full enteral feeds by day 5. No harm was seen when residual checks were not performed. • In the absence of a clinical benefit to the routine performance of gastric residuals in very low birth weight infants, it may be appropriate to discontinue their use and instead check residuals when clinical concern of pathology arises.

The association between calf birth weight and the postcalving performance of its dairy dam in the absence of dystocia.

The objective of the study was to quantify the association between the birth weight of a calf and the subsequent performance of its dairy dam in the absence of any recorded calving assistance. A total of 11,592 lactation records from 4,549 spring-calving dairy cows were used. The association between a series of quantitative cow performance metrics (dependent variable) and calf birth weight (independent variable) was determined using linear mixed models; logistic regression was used where the dependent variable was binary. Nuisance factors in the models were calf sex, heterosis coefficient of both the cow and calf, dry period length immediately before the birth of the calf, cow age at calving relative to the median cow age per parity, breed proportion of the cow, cow live weight between 100 and 200 d of lactation relative to the mean cow weight per parity, and contemporary group. Calf birth weight was included in the model as either a continuous or a categorical variable. Primiparous and multiparous cows were analyzed separately. Mean (SD) calf birth weight was 36.2 (6.8) kg. In primiparous cows, calf birth weight was associated with milk yield in the first 60 d of lactation, calving to first service interval, calving body weight (BW), and both nadir BW and body condition score (BCS). In multiparous cows, calf birth weight was associated with total milk, fat, and protein yield in the first 60 and 305 d of lactation, peak milk yield, total milk solids, both calving and nadir BW, and BCS loss from calving to nadir. Relative to primiparous cows that gave birth to calves weighing 34 to 37 kg (i.e., population mean), their contemporaries who gave birth to calves that weighed 15 to 29 kg produced 9.82 kg more milk in the first 60 d of lactation, had a 2-d shorter interval to first service, and were 8.08 kg and 5.51 kg lighter at calving and nadir BW, respectively; the former was also 0.05 units lower in BCS (5-point scale, 1 = emaciated and 5 = obese) at nadir. Relative to multiparous cows that gave birth to calves that were 34 to 37 kg birth weight, multiparous cows that gave birth to calves that were 15 to 29 kg yielded 59.63 kg, 2.44 kg, and 1.76 kg less milk, fat, and protein, respectively, in the first 60 d of lactation; produced 17.69 kg less milk solids throughout the 305-d lactation; and were also 10.49 kg lighter at nadir and lost 0.01 units more BCS to nadir. In a separate series of analyses, sire breed was added to the model as a fixed effect with and without calf birth weight. When calf birth weight was not adjusted for, 60-d milk yield for multiparous cows who gave birth to calves sired by a traditional beef breed (i.e., Angus, Hereford) produced 59.63 kg more milk than multiparous cows who gave birth to calves sired by a Holstein-Friesian. Hence, calf birth weight is associated with some subsequent dam performance measures; however, where associations do exist, the effect is biologically small.

The TGM2 inhibitor cysteamine hydrochloride does not impact corneal epithelial and stromal wound healing in vitro and in vivo.

Corneal wound healing is integral for resolution of corneal disease or for post-operative healing. However, corneal scarring that may occur secondary to this process can significantly impair vision. Tissue transglutaminase 2 (TGM2) inhibition has shown promising antifibrotic effects and thus holds promise to prevent or treat corneal scarring. The commercially available ocular solution for treatment of ocular manifestations of Cystinosis, Cystaran®, contains the TGM2 inhibitor cysteamine hydrochloride (CH). The purpose of this study is to assess the safety of CH on corneal epithelial and stromal wounds, its effects on corneal wound healing, and its efficacy against corneal scarring following wounding. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were first used to quantify and localize TGM2 expression in the cornea. Subsequently, (i) the in vitro effects of CH at 0.163, 1.63, and 16.3 mM on corneal epithelial cell migration was assessed with an epithelial cell migration assay, and (ii) the in vivo effects of application of 1.63 mM CH on epithelial and stromal wounds was assessed in a rabbit model with ophthalmic examinations, inflammation scoring, color and fluorescein imaging, optical coherence tomography (OCT), and confocal biomicroscopy. Post-mortem assessment of corneal tissue post-stromal wounding included biomechanical characterization (atomic force microscopy (AFM)), histology (H&E staining), and determining incidence of myofibroblasts (immunostaining against α-SMA) in wounded corneal tissue. TGM2 expression was highest in corneal epithelial cells. Application of the TGM2 inhibitor CH did not affect in vitro epithelial cell migration at the two lower concentrations tested. At 16.3 mM, decreased cell migration was observed. In vivo application of CH at 57 mM was well tolerated and did not adversely affect wound healing. No difference in corneal scarring was found between CH treated and vehicle control eyes. This study shows that the TGM2 inhibitor CH, at the FDA-approved dose, is well tolerated in a rabbit model of corneal wound healing and does not adversely affect epithelial or stromal wound healing. This supports the safe use of this medication in Cystinosis patients with open corneal wounds. CH did not have an effect on corneal scarring in this study, suggesting that Cystaran® administration to patients with corneal wounds is unlikely to decrease corneal fibrosis.

Birmingham hip resurfacing: a systematic review of outcomes at minimum 10-years follow-up.

Although controversy surrounding the use of metal-on-metal (MoM) arthroplasty implants continues to exist, satisfactory clinical and radiological outcomes have been reported following Birmingham Hip Resurfacing (BHR) at long-term follow-up, leading to an Orthopaedic Data Evaluation Panel (ODEP) rating of 13A. The purpose of this study was to systematically review the literature to evaluate the functional outcomes, radiological outcomes and revision rates following BHR at a minimum of 10 years follow-up. Using the PRISMA guidelines, two independent reviewers performed a literature search using Pubmed, Embase and Scopus databases. Only studies reporting on outcomes of BHR with a minimum of 10 years' follow-up were considered for inclusion. A total of 12 studies including 7132 hips (64.8% males), with mean follow-up of 11.5 years (10-15.3), met our inclusion criteria. Of included patients, 94.3% of patient underwent BHR for osteoarthritis at a mean age was 52.0 years (48-52). At final follow-up, 96% of patients reported being satisfied with their BHR, with mean Harris Hip Scores of 93.6 and Oxford Hip Scores of 16.5. Rates of radiological femoral neck narrowing of greater than 10% and non-progressive radiological loosening were reported as 2.0% and 3.8% respectively. At final follow-up, the overall revision rate was 4.9% (334/7132), deep infection rate was 0.4%, metal allergy/insensitivity rate was 1.6%, metal reaction rate was 0.3%, rate of peri-prosthetic fracture was 0.9% and aseptic loosening rates were 1.6%. This systematic review demonstrates that BHR results in satisfactory clinical outcomes, acceptable implant survivorship, low complication rates and modest surgical revision rates in the long-term at minimum 10-year follow-up.

Zinc as a non-hormonal contraceptive: an alternative to the copper intrauterine device (IUD).

In brief: The many side effects of current contraceptives leave a large proportion of women without adequate protection. This study shows that zinc, a highly physiologically compatible metal, provides effective long-acting reversible contraception in rats, without requiring the use of hormones. Abstract: Long-acting and reversible contraceptives (LARC) are the most widely used form of female contraception worldwide; however, they have significant side effects that often result in early removal. Most LARCs are hormonal, but the use of exogenous hormones is not suitable for all women and causes side effects in many others. The copper IUD (CuIUD) is the only non-hormonal LARC, but a large proportion of users suffer severe side effects. This study proposes the use of zinc as a suitable alternative to the CuIUD. A rat intrauterine device (IUD) model was established to test the efficacy of a zinc IUD (ZnIUD) against a CuIUD. The IUD was surgically implanted into one uterine horn while the other remained untreated. Both the ZnIUD and CuIUD resulted in zero implantation sites which were significantly fewer compared to non-treated horns. Histological assessment revealed damage and inflammation in the endometrium of CuIUD-treated horns but only minor epithelial changes in ZnIUD-treated horns. This suggests ZnIUDs may not share the side effect profile of the CuIUD. To test the long-term efficacy of the ZnIUD, rats had a ZnIUD surgically implanted into both horns and cohoused with males for 3 months. These rats mated regularly but did not get pregnant, confirming long-term effectiveness. Reversibility of the ZnIUD was also established, as removal of the ZnIUD after 3 months resulted in no significant difference in the number of implantation sites between treated and untreated horns. This study demonstrated the contraceptive efficacy of zinc and its potential as a LARC.

Re-assessing the importance of linear type traits in predicting genetic merit for survival in an aging Holstein-Friesian dairy cow population.

The cumulative improvement achieved in the genetic merit for reproductive performance in dairy populations will likely improve dairy cow longevity; therefore, it is time to reassess whether linear type traits are still suitable predictors of survival in an aging dairy cow population. The objective of the present study was therefore to estimate the genetic correlations between linear type traits and survival from one parity to the next and, in doing so, evaluate if those genetic correlations change with advancing parity. After edits, 152,894 lactation survival records (first to ninth parity) were available from 52,447 Holstein-Friesian cows, along with linear type trait records from 52,121 Holstein-Friesian cows. A series of bivariate random regression models were used to estimate the genetic covariances between survival in different parities and each linear type trait. Heritability estimates for survival per parity ranged from 0.02 (SE = 0.004; first parity) to 0.05 (SE = 0.01; ninth parity). Pairwise genetic correlations between survival among different parities varied from 0.42 (first and ninth parity) to 1.00 (eighth to ninth parity), with the strength of these genetic correlations being inversely related to the interval between the compared parities. The genetic correlations between survival and the individual linear type traits varied across parities for 9 of the 20 linear type traits examined, but the correlations with only 3 of these linear type traits strengthened as the cows aged; these 3 traits were rear udder height, teat length, and udder depth. Given that linear type traits are frequently scored in first parity and are genetically correlated with survival in older parities, they may be suitable early predictors of survival, especially for later parity cows. Additionally, the direction of the genetic correlations between survival and rear udder height, teat length, and udder depth did not change between parities; hence, selection for survival in older parities using these linear type traits should not hinder genetic improvement for survival in younger parities.

Exploiting genetic variability in the trajectory of lactation yield and somatic cell score with each progressing parity.

The inclusion of reproductive performance in dairy cow breeding schemes has resulted in a cumulative improvement in genetic merit for reproductive performance; this improvement should manifest in longer productive lives through a reduced requirement for involuntary culling. Nonetheless, the average length of dairy cow productive life has not changed in most populations, suggesting that risk factors for culling, especially in older cows, are possibly more associated with lower yield or high somatic cell score (SCS) than compromised reproductive performance. The objective of the present study was to understand the dynamics of lactation yields and SCS in dairy cows across parities and, in doing so, quantify the potential to alter this trajectory through breeding. After edits, 3,470,520 305-d milk, fat, and protein yields, as well as milk fat and protein percentage and somatic cell count records from 1,162,473 dairy cows were available for analysis. Random regression animal models were used to identify the parity in which individual cows reached their maximum lactation yields, and highest average milk composition and SCS; also estimated from these models were the (co)variance components for yield, composition, and SCS per parity across parities. Estimated breeding values for all traits per parity were calculated for cows reaching ≥fifth parity. Of the cows included in the analyses, 91.0%, 92.2%, and 83.4% reached maximum milk, fat, and protein yield in fifth parity, respectively. Conversely, 95.9% of cows reached their highest average fat percentage in first parity and 62.9% of cows reached their highest average protein percentage in third parity. In contrast to both milk yield and composition traits, 98.4% of cows reached their highest average SCS in eighth parity. Individual parity estimates of heritability for milk yield traits, milk composition, and SCS ranged from 0.28 to 0.44, 0.47 to 0.69, and 0.13 to 0.23, respectively. The strength of the genetic correlations per trait among parities was inversely related to the interval between the parities compared; the weakest genetic correlation was 0.67 (standard error = 0.02) between milk yield in parities 1 and 8. Eigenvalues and eigenfunctions of the additive genetic covariance matrices for all investigated traits revealed potential to alter the trajectory of parity profiles for milk yield, milk composition, and SCS. This was further demonstrated when evaluating the trajectories of animal estimated breeding values per parity.

Are subjectively scored linear type traits suitable predictors of the genetic merit for feed intake in grazing Holstein-Friesian dairy cows?

Measuring dry matter intake (DMI) in grazing dairy cows using currently available techniques is invasive, time consuming, and expensive. An alternative to directly measuring DMI for use in genetic evaluations is to identify a set of readily available animal features that can be used in a multitrait genetic evaluation for DMI. The objectives of the present study were thus to estimate the genetic correlations between readily available body-related linear type traits and DMI in grazing lactating Holstein-Friesian cows, but importantly also estimate the partial genetic correlations between these linear traits and DMI, after adjusting for differences in genetic merit for body weight. Also of interest was whether the predictive ability derived from the estimated genetic correlations materialized upon validation. After edits, a total of 8,055 test-day records of DMI, body weight, and milk yield from 1,331 Holstein-Friesian cows were available, as were chest width, body depth, and stature from 47,141 first lactation Holstein-Friesian cows. In addition to considering the routinely recorded linear type traits individually, novel composite traits were defined as the product of the linear type traits as an approximation of rumen volume. All linear type traits were moderately heritable, with heritability estimates ranging from 0.27 (standard error = 0.14) to 0.49 (standard error = 0.15); furthermore, all linear type traits were genetically correlated (0.29 to 0.63, standard error 0.14 to 0.12) with DMI. The genetic correlations between the individual linear type traits and DMI, when adjusted for genetic differences in body weight, varied from -0.51 (stature) to 0.48 (chest width). These genetic correlations between DMI and linear type traits suggest linear type traits may be useful predictors of DMI, even when body weight information is available. Nonetheless, estimated genetic merit of DMI derived from a multitrait genetic evaluation of linear type traits did not correlate strongly with actual DMI in a set of validation animals; the benefit was even less if body weight data were also available.

Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.

BACKGROUND: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population. RESULTS: A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy. CONCLUSIONS: In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.

Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Upscaling e-mental health in Europe: a six-country qualitative analysis and policy recommendations from the eMEN project.

E-mental health (eMH) encompasses the use of digital technologies to deliver, support, or enhance mental health services. Despite the growing evidence for the effectiveness of eMH interventions, the process of implementation of eMH solutions in healthcare remains slow throughout Europe. To address this issue, the e-Mental Health Innovation and Transnational Implementation Platform North-West Europe (eMEN) project was initiated to increase the dissemination and quality of eMH services in Europe. In this project, status analyses regarding eMH in the six participating countries (i.e., Belgium, France, Germany, Ireland, The Netherlands, and the UK) were conducted and eight recommendations for eMH were developed. Expert teams from the six participating countries conducted status analyses regarding the uptake of eMH based on a narrative literature review and stakeholder interviews. Based on these status analyses, the eMEN consortium developed eight policy recommendations to further support the implementation of eMH in Europe. The status analyses showed that the participating countries are in different stages of implementing eMH into mental healthcare. Some barriers to implementing eMH were common among countries (e.g., a limited legal and regulatory framework), while others were country-specific (e.g., fragmented, federal policies). The policy recommendations included fostering awareness, creating strong political commitment, and setting reliable standards related to ethics and data security. The eMEN project has provided the initial recommendations to guide political and regulatory processes regarding eMH. Further research is needed to establish well-tailored implementation strategies and to assess the generalizability of the recommendations beyond the countries involved in the eMEN project.

Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Genetic and nongenetic factors associated with lactation length in seasonal-calving, pasture-based dairy cows.

Lactation yield estimates standardized to common lactation lengths of 270-d or 305-d equivalents are commonly used in management decision support tools and dairy cow genetic evaluations. The use of such measurements to quantify the (genetic) merit of individual cows fails to penalize cows that do not reach the standardized lactation length, or indeed reward cows that lactate for more than the standardized lactation length. The objective of the present study was to quantify the genetic and nongenetic factors associated with lactation length in seasonal-calving, pasture-based dairy cows. A total of 616,350 lactation length records from 285,598 Irish cows were used. Linear mixed models were used to quantify the associations between lactation length and calving month, parity, age at calving, previous dry period length, calving difficulty score, heterosis, recombination loss, breed, and herd size, as well as to estimate the genetic and residual variance components of lactation length. The median lactation length in the edited data set was 288 d, with 27% of cows achieving lactations of at least 305 d. Relative to cows calving in January, the lactations of cow calving in February, March, or April was, on average, 4.2, 12.7, and 21.9 d shorter, respectively. The lactation length of a first parity cow was, on average, 7.8, 8.6, and 8.4 d shorter than that of second, third, and fourth parity cows, respectively. Norwegian Red and Montbéliarde cows had, on average, a 4.7- and 1.6-d shorter lactation than Holstein-Friesian cows, respectively. The heritability estimate, coefficient of genetic variation, and repeatability estimate of lactation length were 0.02, 1.2%, and 0.04, respectively. Based on the genetic standard deviation for lactation length estimated in the present study (3.3 d), cows ranked in the top 20% for genetic merit for lactation length would be expected to have lactations 9.2 d longer than cows in the bottom 20%, demonstrating exploitable genetic variability. Given the vast array of genetic and nongenetic factors associated with lactation length, an approach which combines improved management practices and selective breeding may be an efficient and effective strategy to lengthen lactations.

A behaviour change package to prevent hand dermatitis in nurses working in the National Health Service: results of a cluster randomized controlled trial.

BACKGROUND: Occupational hand dermatitis poses a serious risk for nurses. OBJECTIVES: To evaluate the clinical and cost-effectiveness of a complex intervention in reducing the prevalence of hand dermatitis in nurses METHODS: This was a cluster randomized controlled trial conducted at 35 hospital trusts, health boards or universities in the UK. Participants were (i) first-year student nurses with a history of atopic conditions or (ii) intensive care unit (ICU) nurses. Participants at intervention sites received access to a behavioural change programme plus moisturizing creams. Participants at control sites received usual care. The primary outcome was the change of prevalent dermatitis at follow-up (adjusted for baseline dermatitis) in the intervention vs. the control group. Randomization was blinded to everyone bar the trials unit to ensure allocation concealment. The trial was registered on the ISRCTN registry: ISRCTN53303171. RESULTS: Fourteen sites were allocated to the intervention arm and 21 to the control arm. In total 2040 (69·5%) nurses consented to participate and were included in the intention-to-treat analysis. The baseline questionnaire was completed by 1727 (84·7%) participants. Overall, 789 (91·6%) ICU nurses and 938 (84·0%) student nurses returned completed questionnaires. Of these, 994 (57·6%) had photographs taken at baseline and follow-up (12-15 months). When adjusted for baseline prevalence of dermatitis and follow-up interval, the odds ratios (95% confidence intervals) for hand dermatitis at follow-up in the intervention group relative to the controls were 0·72 (0·33-1·55) and 0·62 (0·35-1·10) for student and ICU nurses, respectively. No harms were reported. CONCLUSIONS: There was insufficient evidence to conclude whether our intervention was effective in reducing hand dermatitis in our populations. Linked Comment: Brans. Br J Dermatol 2020; 183:411-412.

Coccidioides (spherulin) skin testing in patients with pulmonary coccidioidomycosis in an endemic region†.

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States. Intact cellular immunity is critical to the control of this infection. A recently released reformulated spherulin antigen (Spherusol; Nielsen BioSciences, Inc.) was approved to detect delayed-type hypersensitivity, which implies the presence of cellular immunity, to Coccidioides species. We aimed to summarize our experience with this test in patients with primary pulmonary coccidioidomycosis. We retrospectively reviewed clinical data for all patients with primary pulmonary coccidioidomycosis who had a Coccidioides (spherulin) skin test (CST) placed at our institution between January 1, 2015, and August 31, 2017. During the study period, 172 patients had a CST placed, and 122 met our inclusion criteria for proven or probable pulmonary coccidioidomycosis. Of these 122, 88 (72.1%) had a positive CST result and 34 (27.9%) had a negative result. In the positive CST group, 74 of the 79 treated patients (93.7%) had antifungal treatment stopped, 1 of whom (1.4%) had relapsed infection. In contrast, 27 of the 33 treated patients in the negative CST group (81.8%) had their antifungal treatment stopped, and none had a relapse. Seven patients overall (5.7%), all of whom had a positive CST, experienced mild local adverse reactions to the CST. Although previous controlled studies of CST showed sensitivity and specificity greater than 98%, our real-world experience with the CST showed lower rates of positivity. Negative CST results did not predict relapse with antifungal agent withdrawal.

An interdisciplinary and catchment approach to enhancing urban flood resilience: a Melbourne case.

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue 'Urban flood resilience'.

The Neuroanatomy of Autism Spectrum Disorder Symptomatology in 22q11.2 Deletion Syndrome.

22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition associated with a high prevalence of neuropsychiatric conditions that include autism spectrum disorder (ASD). While evidence suggests that clinical phenotypes represent distinct neurodevelopmental outcomes, it remains unknown whether this translates to the level of neurobiology. To fractionate the 22q11.2DS phenotype on the level of neuroanatomy, we examined differences in vertex-wise estimates of cortical volume, surface area, and cortical thickness between 1) individuals with 22q11.2DS (n = 62) and neurotypical controls (n = 57) and 2) 22q11.2DS individuals with ASD symptomatology (n = 30) and those without (n = 25). We firstly observed significant differences in surface anatomy between 22q11.2DS individuals and controls for all 3 neuroanatomical features, predominantly in parietotemporal regions, cingulate and dorsolateral prefrontal cortices. We also established that 22q11.2DS individuals with ASD symptomatology were neuroanatomically distinct from 22q11.2DS individuals without ASD symptoms, particularly in brain regions that have previously been linked to ASD (e.g., dorsolateral prefrontal cortices and the entorhinal cortex). Our findings indicate that different clinical 22q11.2DS phenotypes, including those with ASD symptomatology, may represent different neurobiological subgroups. The spatially distributed patterns of neuroanatomical differences associated with ASD symptomatology in 22q11.2DS may thus provide useful information for patient stratification and the prediction of clinical outcomes.

A growing challenge: The rise of femoral periprosthetic fractures - An 11-year observational study.

INTRODUCTION: The demand for joint arthroplasty has risen as our elderly population increases and ages. With this so to has the number of patients suffering periprosthetic fractures (PPF). The aim of our study was to quantify the burden of PPF and provide an up to date reference of the epidemiology of PPF in Ireland. We also sought to assess length of stay (LOS), resource utilisation and mortality associated with this cohort of patients. METHODS: An eleven-year retrospective observational study was conducted of a consecutive series of patients treated for a femoral PPF. Costs were obtained from activity based tariffs provided by the hospital inpatient enquiry system and mortality was confirmed using the national death events publication system. RESULTS: Over the 11-year study period 174 procedures for a femoral PPF were performed. Mean age of patients was 77.6 years (SD 11.1 years) with 44.7% male. Median ASA grade was 3 (range 1-4) and mean LOS was 19 days. There was a 700% increase in patients undergoing surgery for a PPF over the study period. The mean cost of care was €24,413 in 2017. Thirty-day mortality was 2.9% while one-year mortality was 12.4%. CONCLUSIONS: PPF occur in an elderly comorbid cohort of patients. Care of these patients now makes up a considerable part of the orthopaedic workload and consumes a significant portion of healthcare resources. Patients should be treated in tertiary referral centres with surgeons skilled in their management. Better access to rehabilitation is needed.

Improved two-dimensional electrophoretic mapping of Japanese human hair proteins; application to curved and straight Japanese human hairs; and protein identification by MALDI MS and MS/MS quadrupole time-of-flight mass spectrometry.

OBJECTIVES: To evaluate improved protein extraction and two-dimensional electrophoresis (2DE) separation methods with Japanese reference human hair (JRH); to determine whether fibre curvature is related to protein composition in curly and straight Japanese women's human hair (JHH) samples; and to identify proteins from JRH 2DE maps and expression differences between curly and straight JHH. METHODS: Hair keratin and keratin-associated proteins (KAPs) were extracted intact with dithiothreitol or tris(2-carboxyethyl) phosphine from JRH or from curved or straight JHH. Extracted proteins were isoelectric-focused on first-dimensional pH gradient gel strips, then separated by molecular weight on laboratory-made, second-dimension, large format gels. The software compared protein abundance between duplicate 2DE gels of curved and straight JHH. Thirty-eight proteins from a JRH 2DE gel were enzyme-cleaved for MALDI-TOF-MS analysis to determine peptide composition, and where possible, de novo sequencing gave peptide sequence data. An in-house human hair protein database incorporating ninety-eight annotated protein sequences assisted MS analysis. RESULTS: 2DE gels of tris(2-carboxyethyl) phosphine-extracted JRH improved keratin and KAP resolution and number compared to those of dithiothreitol-extracted JRH and published commercially made second-dimensional gels. Silver-stained 2DE gels of the straight or curved JHH sets were remarkably similar. Over-staining to reveal basic proteins caused poor resolution of the major acidic protein classes. Software comparisons of fifty-nine resolved proteins revealed two were significantly different in abundance between curved and straight hairs but in insufficient amounts for MS analysis. MS identified twelve proteins from a JRH CBBG-stained 2DE gel: six type II keratins, three type I keratins and three high sulphur proteins. A further eight were potential conformational isoforms and isoelectric variants of the identified proteins bringing the total to twenty identified or partially identified proteins. CONCLUSION: Root-end human hair extraction with tris(2-carboxyethyl) phosphine improves protein resolution and visualizes more proteins on large format 2DE gels. The two minor protein differences between duplicate straight or curved JHH 2DE gels were unlikely to change fibre structure from straight to curved hair. MS results confirmed that multiple isoforms exist of various hair proteins. Low sequence coverage prevented distinction between members in rows of homologous protein spots of similar molecular weight.

OBJECTIFS: évaluer l'amélioration de l'extraction de protéines et les méthodes de séparation bidimensionnelle par électrophorèse (2DE) avec des cheveux humains de référence Japonais (JRH), déterminer si la courbure de la fibre est liée à la composition protéique dans les échantillons de cheveux humains des Japonaises (JHH) bouclés et raides et identifier les protéines issues des cartes JRH 2DE et les différences d'expression entre les JHH bouclés et raides. MÉTHODES: la kératine des cheveux et les protéines associées à la kératine (KAP) ont été extraites intactes avec du dithiothréitol ou du tris (2-carboxyéthyl) phosphine des JRH ou des JHH bouclés ou raides. Les protéines extraites ont subi une focalisation isoélectrique sur des bandes de gel à gradient de pH unidimensionnelles, puis ont été séparées par poids moléculaire sur des gels bidimensionnels de grand format, fabriqués en laboratoire. Le logiciel a comparé l'abondance des protéines entre les deux duplicatas de gels 2DE des JHH bouclés et raides. Trente-huit protéines provenant d'un gel 2DE JRH ont été clivés par enzyme pour l'analyse MALDI-TOF-MS afin de déterminer la composition des peptides, et dans la mesure du possible, un séquençage de novo a donné des données de séquence des peptides. Une base de données interne des protéines capillaires humaines incorporant 98 séquences de protéines annotées a aidé l'analyse MS. RÉSULTATS: les gels 2DE de JRH extraits par le tris (2-carboxyéthyl) ont amélioré la résolution et le nombre de la kératine et du KAP par rapport à ceux du JRH extrait par le dithiothréitol et des gels bidimensionnels fabriqués commercialement. Les gels 2DE à coloration argentée des ensembles de JHH raides ou bouclés étaient remarquablement similaires. La sur-coloration pour révéler les protéines de base a provoqué une mauvaise résolution des principales classes de protéines acides. Les comparaisons logicielles des 59 protéines résolues ont révélé que deux présentaient une différence significative d'abondance entre les cheveux bouclés et raides, mais en quantités insuffisantes pour une analyse MS. La MS a identifié douze protéines provenant d'un gel 2DE coloré CBBG JRH : six kératines de type II, trois kératines de type I et trois protéines à forte teneur en soufre. Huit autres étaient des isoformes conformationnels potentiels et des variantes isoélectriques des protéines identifiées, ramenant le total à 20 protéines identifiées ou partiellement identifiées. CONCLUSION: l'extraction des cheveux humains à la racine avec du tris (2-carboxyéthyl) phosphine améliore la résolution des protéines et permet de visualiser plus de protéines sur les gels 2DE grand format. Les deux différences de protéines mineures entre les duplicatas des gels 2DE JHH raides ou bouclés étaient peu susceptibles de changer la structure des fibres de cheveux raides à bouclés. Les résultats de la MS ont confirmé qu'il existe plusieurs isoformes de diverses protéines capillaires. Une faible couverture de séquence a empêché la distinction entre les protéines homologues de poids moléculaire similaire.