Animal board invited review: Improving animal health and welfare in the transition of livestock farming systems: Towards social acceptability and sustainability.

The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasises the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analysing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers' willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organisation of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

Periventricular hemorrhagic infarction in preterm neonates: Etiology and time of development.

BACKGROUND: To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates. METHODS: A retrospective study of obstetric and delivery associated risk factors included neonates (<35 gestational weeks) with severe IVH/PVHI (n = 120) and a prospectively collected control group (n = 50). The children were divided into: (1) antenatal onset group (n = 27) with insult visible on cerebral ultrasonography within the first 12 hours of birth or periventricular cystic changes visible in PVHI within the first 3 days; (2) neonatal onset group (n = 70) with insult diagnosed after initial normal findings or I-II grade IVH, and (3) unknown time-onset group (n = 23) with insult visible at > 12 h of age. RESULTS: The mothers of the antenatal onset group had significantly more bacterial infections before delivery compared to the neonatal onset group: 20/27 (74.1%) versus 23/69 (33.3%), (odds ratio (OR) 5.7 [95% confidence interval 2.1-16]; p = 0.0008) or compared to the control group (11/50 (22%); OR 11 [2.8-42]; p = 0.0005). Placental histology revealed chorioamnionitis more often in the antenatal compared to the neonatal onset group (14/21 (66.7%) versus 16/42 (38.1%), respectively; OR 3.7 [1.18-11]; p = 0.025). Neonates with neonatal development of severe IVH/PVHI had significantly more complications during delivery or intensive care. CONCLUSIONS: Bacterial infection during pregnancy is an important risk factor for development of antenatal onset severe IVH or PVHI. In neonates born to mothers with severe bacterial infection during pregnancy, cerebral ultrasonography is indicated for early detection of severe IVH or PVHI.

Dedicated teams to optimize quality and safety of surgery: A systematic review.

BACKGROUND: A dedicated operating team is defined as a surgical team consisting of the same group of people working together over time, optimally attuned in both technical and/or communicative aspects. This can be achieved through technical and/or communicative training in a team setting. A dedicated surgical team may contribute to the optimization of healthcare quality and patient safety within the perioperative period. METHOD: A systematic review was conducted to evaluate the effects of a dedicated surgical team on clinical and performance outcomes. MEDLINE and Embase were searched on 23 June 2022. Both randomized controlled trials (RCTs) and non-randomized studies (NRSs) were included. Primary outcomes were mortality, complications and readmissions. Secondary outcomes were costs and performance measures. RESULTS: Fourteen studies were included (RCTs n = 1; NRSs n = 13). Implementation of dedicated operating teams was associated with improvements in mortality, turnover time, teamwork, communication and costs. No significant differences were observed in readmission rates and length of hospital stay. Results regarding duration, glitch counts and complications of surgery were inconclusive. Limitations include study conduct and heterogeneity between studies. CONCLUSIONS: The institution of surgical teams who followed communicative and/or technical training appeared to have beneficial effects on several clinical outcome measures. Dedicated teams provide a feasible way of improving healthcare quality and patient safety. A dose-response effect of team training was reported, but also a relapse rate, suggesting that repetitive training is of major concern to high-quality patient care. Further studies are needed to confirm these findings, due to limited level of evidence in current literature. PROSPERO REGISTRATION NUMBER: CRD42020145288.

Nutritional status and out-of-hospital mortality in vascular surgery patients.

BACKGROUND: Malnutrition is often present in vascular surgery patient during hospital admission. The present evidence of the consequence malnutrition has on morbidity and mortality is limited. AIM: The purpose of this study was to determine the effect of nutritional status on out-of-hospital mortality in vascular surgery patients. METHODS: An observational cohort study was performed, studying non-cardiac vascular surgery patients surviving hospital admission 18 years or older treated in Boston, Massachusetts, USA. The exposure of interest was nutritional status categorized as well nourished, at-risk for malnutrition, nonspecific malnutrition or protein-energy malnutrition. The all cause 90-day mortality following hospital discharge was the primary outcome. Adjusted odds ratios were estimated by multivariable logistic regression models. RESULTS: This cohort included 4432 patients comprised of 48% women and a mean age 61.7 years. After evaluation by a registered dietitian, 3819 patients were determined to be well nourished, 215 patients were at-risk for malnutrition, 351 had non-specific malnutrition and 47 patients had protein-energy malnutrition. After adjustment for age, sex, ethnicity, medical versus surgical Diagnosis Related Group type, Deyo-Charlson index, length of stay, and vascular Current Procedural Terminology code category, the 90-day post-discharge mortality odds ratio for patients with non-specific malnutrition OR 1.96 (95%CI 1.21, 3.17) and for protein-energy malnutrition OR 3.58 (95%CI 1.59, 8.06), all relative to patients without malnutrition. DISCUSSION: Nutritional status is a strong predictor of out-of-hospital mortality. This suggests that patient with vascular disease suffering from malnutrition could benefit from more intensified In-hospital and out-of-hospital dietary guidance and interventions.

It's all about timing, early treatment with hyperbaric oxygen therapy and corticosteroids is essential in acute acoustic trauma.

BACKGROUND: Acute acoustic trauma (AAT) is an acute hearing impairment caused by intense noise-impact. The current management strategy for AAT with substantial hearing loss in the Dutch military is the combination therapy with corticosteroids and hyperbaric oxygen therapy (HBOT). In a previous study, early initiation of the combination therapy was associated with better outcomes. Therefore, we performed a new analysis to assess the difference in hearing outcome between patients in whom combination therapy was started within two days, versus after more than two days. METHODS: A retrospective analysis was performed on military patients diagnosed with AAT with substantial hearing loss who presented between February 2018 and March 2020. Absolute and relative hearing improvement between first and last audiograms were calculated for all affected frequencies (defined as loss of ≥20 dB on initial audiogram). We also determined the amount of patients who recovered to the level of Dutch military requirement, and performed speech discrimination tests. RESULTS: In this analysis, 30 male patients (49 ears) with AAT were included. The median age was 24.5 years (IQR 23-29). The median time to initiation of therapy with corticosteroids and HBOT were one and two days, respectively. HBOT was started within two days in 31 ears, and after more than two days in 18 ears. The mean absolute and relative hearing gains were 18.8 dB (SD 14.6) and 46.8% (SD 31.3) on all affected frequencies. The 100% discrimination/speech perception level improved from 64.0 dB to 51.7 dB (gain 12.3 dB ± 14.1). There was significantly more improvement in absolute and relative hearing improvement when HBOT was started in ≤2 days, compared to >2 days. CONCLUSION: Our analysis shows results in favor of early initiation (≤2 days) of the combination treatment of HBOT and corticosteroids in patients with AAT.

Eosinopenia and post-hospital outcomes in critically ill non-cardiac vascular surgery patients.

BACKGROUND AND AIMS: Eosinopenia is a marker for acute inflammation. We hypothesized that eosinopenia at Intensive Care Unit (ICU) admission in vascular surgery patients who receive critical care, would be associated with increased mortality following hospital discharge. METHODS AND RESULTS: We performed a two-center observational cohort study of critically ill, non-cardiac adult vascular surgery patients who received treatment in Boston between 1997 and 2012 and survived hospital admission. The consecutive sample included 5083 patients (male 57%, white 82%, mean age [SD] 61.6 [17.4] years). The exposure was Absolute eosinophil count measured within 24 h of admission to the ICU and categorized as ≤10 cells/µL, 11-50 cells/µL, 51-100 cells/µL, 101-350 cells/µL (normal range), and >350 cells/µL. The primary outcome was all-cause mortality within 90 days of hospital discharge. The secondary outcome was discharge to home following hospitalization. 90-day post-discharge mortality was 6.7%, and 12.9% of patients were readmitted within 30 days. After multivariable adjustment, patients with eosinopenia (≤10 cells/µL) have a 90-day post-discharge mortality OR of 1.97 (95%CI 1.42, 2.73; P < 0.001) relative to patients with an absolute eosinophil count of 101-350 cells/µL. Further, after multivariable adjustment, patients with eosinopenia (≤10 cells/µL) have a 25% lower odds of discharge to home compared to patients with an absolute eosinophil count of 101-350 cells/µL [OR = 0.71 (CI 95% 0.59-0.85); P < 0.001]. CONCLUSION: Eosinopenia at ICU admission is a robust predictor of increased mortality and lower likelihood of discharge to home in vascular surgery patients treated with critical care who survive hospitalization.

The number of CAG and GGN triplet repeats in the Androgen Receptor gene exert combinatorial effect on hormonal and sperm parameters in young men.

Androgen receptor (AR) is a transcription factor that is activated upon binding to testosterone (T) and is implicated in regulating the expression of reproduction-related genes. The human AR gene (Xq11-12) spans 186,588 bp and eight exons. N-terminal transactivation domain of the encoded AR protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8-37 CAG-repeats) and a polyglycine tract (encoded by 10-30 GGN-repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population-based cohort of Baltic young men (n = 974; aged 20.1 ± 2.1 years). We designed an assay to amplify and detect simultaneously the variants of both polymorphic repeats. The study revealed that elongated AR CAG tract was associated with lower FSH (linear regression: p = 0.0002, effect per repeat -0.056 IU/L). As a novel finding, the carriers of GGN-stretch with ≥24 repeats showed a trend for decreased sperm concentration (p = 0.027). Although neither of the variants exhibited an isolated effect on circulating T, their allelic combinations modulated serum T levels, as well as sperm concentration. The lowest T was measured for men carrying the AR gene with long CAG (n ≥ 25) and short GGN (n ≤ 21) repeat tracts (mean 18.8 vs. 25.5-28.6 nmol/L for the other AR variants, p = 0.017). The lowest sperm concentration was detected among individuals with both elongated repetitive stretches (CAG, n ≥ 25 and GGN, n ≥ 24; mean 49.0 vs. 68.4-72.1 mill/mL for the other variants; p = 0.00059). The innovative study design enabled to clearly demonstrate a combinatory impact of CAG and GGN repeat lengths at male reproductive parameters. As AR regulates transcription of over 900 genes in many tissues and organs, the combinatory effects of these common repeat-length variants on male physiology in the wider context and across lifetime are still to be assessed.

Doubly robust nonparametric inference on the average treatment effect.

Doubly robust estimators are widely used to draw inference about the average effect of a treatment. Such estimators are consistent for the effect of interest if either one of two nuisance parameters is consistently estimated. However, if flexible, data-adaptive estimators of these nuisance parameters are used, double robustness does not readily extend to inference. We present a general theoretical study of the behaviour of doubly robust estimators of an average treatment effect when one of the nuisance parameters is inconsistently estimated. We contrast different methods for constructing such estimators and investigate the extent to which they may be modified to also allow doubly robust inference. We find that while targeted minimum loss-based estimation can be used to solve this problem very naturally, common alternative frameworks appear to be inappropriate for this purpose. We provide a theoretical study and a numerical evaluation of the alternatives considered. Our simulations highlight the need for and usefulness of these approaches in practice, while our theoretical developments have broad implications for the construction of estimators that permit doubly robust inference in other problems.

Development and External Validation of a Model Predicting Death After Surgery in Patients With a Ruptured Abdominal Aortic Aneurysm: The Dutch Aneurysm Score.

OBJECTIVE: The decision whether or not to proceed with surgical intervention of a patient with a ruptured abdominal aortic aneurysm (rAAA) is very difficult in daily practice. The primary objective of the present study was to develop and to externally validate a new prediction model: the Dutch Aneurysm Score (DAS). METHODS: With a prospective cohort of 10 hospitals (n = 508) the DAS was developed using a multivariate logistic regression model. Two retrospective cohorts with rAAA patients from two hospitals (n = 373) were used for external validation. The primary outcome was the combined 30 day and in-hospital death rate. Discrimination (AUC), calibration plots, and the ability to identify high risk patients were compared with the more commonly used Glasgow Aneurysm Score (GAS). RESULTS: After multivariate logistic regression, four pre-operative variables were identified: age, lowest in hospital systolic blood pressure, cardiopulmonary resuscitation, and haemoglobin level. The area under the receiver operating curve (AUC) for the DAS was 0.77 (95% CI 0.72-0.82) compared with the GAS with an AUC of 0.72 (95% CI 0.67-0.77). The DAS showed a death rate in patients with a predicted death rate ≥80% of 83%. CONCLUSIONS: The present study shows that the DAS has a higher discriminative performance (AUC) compared with the GAS. All clinical variables used for the DAS are easy to obtain. Identification of low risk patients with the DAS can potentially reduce turndown rates. The DAS can reliably be used by clinicians to make a more informed decision in dialogue with the patient and their family whether or not to proceed with surgical intervention.

Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts.

STUDY QUESTION: What are the primary causes of severe male factor infertility? SUMMARY ANSWER: Although 40% of all patients showed primary causes of infertility, which could be subdivided into three groups based on the severity of their effect, ~75% of oligozoospermia cases remained idiopathic. WHAT IS KNOWN ALREADY: There are few large-scale epidemiological studies analyzing the causes of male factor infertility. STUDY DESIGN, SIZE, DURATION: A prospective clinical-epidemiological study was conducted at the Andrology Centre, Tartu University Hospital between 2005 and 2013, recruiting male partners of couples failing to conceive a child for over ≥12 months. Among 8518 patients, 1737 (20.4%) were diagnosed with severe male factor infertility. A reference group of fertile controls was comprised of 325 partners of pregnant women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean age of infertility patients and fertile controls was 33.2 ± 7.3 and 31.7 ± 6.3 years, respectively. All participants were examined using a standardized andrology workup, accompanied by a structured medical interview. Hormonal analysis included serum FSH, LH and testosterone. Semen quality was determined in accordance to the World Health Organization recommendations. Cases with spermatozoa concentrations of ≤5 million/ml were screened for chromosomal aberrations and Y-chromosomal microdeletions. MAIN RESULTS AND THE ROLE OF CHANCE: The primary cause of infertility was defined for 695 of 1737 patients (~40%). The analyzed causal factors could be divided into absolute (secondary hypogonadism, genetic causes, seminal tract obstruction), severe (oncological diseases, severe sexual dysfunction) and plausible causal factors (congenital anomalies in uro-genital tract, acquired or secondary testicular damage). The latter were also detected for 11 (3.4%) men with proven fertility (diagnoses: unilateral cryptorchidism, testis cancer, orchitis, mumps orchitis). The causal factors behind the most severe forms of impaired spermatogenesis were relatively well understood; causes were assigned: for aspermia in 46/46 cases (100%), for azoospermia in 321/388 cases (82.7%), and for cryptozoospermia in 54/130 cases (41.5%). In contrast, 75% of oligozoospermia cases remained unexplained. The main cause of aspermia was severe sexual dysfunction (71.7% of aspermia patients). Azoospermia patients accounted for 86.4% of all cases diagnosed with secondary hypogonadism and 97.1% of patients with seminal tract obstruction. Of patients with a known genetic factor, 87.4% had extreme infertility (azoo-, crypto- or aspermia). The prevalence of congenital anomalies in the uro-genital tract was not clearly correlated with the severity of impaired sperm production. Previously defined 'potential contributing factors' varicocele and leukocytospermia were excluded as the primary causes of male infertility. However, their incidence was >2-fold higher (31.0 vs 13.5% and 16.1 vs 7.4%; P < 0.001) in the idiopathic infertility group compared to controls. In addition, the proportions of overweight (or obese) patients and patients suffering from a chronic disease were significantly increased in almost all of the patient subgroups. LIMITATIONS REASONS FOR CAUTION: The study included only subjects with reduced total spermatozoa counts. Thus, these findings cannot be automatically applied to all male factor infertility cases. WIDER IMPLICATIONS OF THE FINDINGS: The novel insights and improved clarity achieved in the comprehensive analysis regarding the absolute, causative and plausible factors behind male infertility, as well as the 'potential contributing factors', will be valuable tools in updating the current clinical guidelines. The study highlights knowledge gaps and reiterates an urgent need to uncover the causes and mechanisms behind, and potential treatments of, oligozoospermic cases, representing the majority of idiopathic infertility patients (86.3%). STUDY FUNDING/COMPETING INTERESTS: The project was financed by the EU through the ERDF, project HAPPY PREGNANCY, no. 3.2.0701.12-004 (M.P., M.L.) and the Estonian Research Council: grants PUT181 (M.P.) and IUT34-12 (M.L.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. TRAIL  REGISTRATION NUMBER: Not applicable.

[How do adolescent inpatients experience seclusion and other coercive measures?]. / Hoe beleven opgenomen adolescenten separatie en andere vormen van dwang?

BACKGROUND: The reduction of coercive measures in psychiatry, particularly of seclusion, is considered to be a matter of some urgency. When policy changes with regard to coercive measures are being considered, the wishes and preferences of patients should be taken into account. Up till now, however, there have not been any studies that have examined how adolescent inpatients feel about coercive measures. AIM: To examine the way adolescent inpatients feel about seclusion and other forms of coercive measures. METHOD: Adolescent inpatients in a Dutch centre for orthopsychiatry (n = 34) were asked about their experiences with and their thoughts on coercive measures in general and on seclusion in particular. RESULTS: Thirty-two respondents took part. More than half of the 18 adolescents who had had prior experiences of coercive measures preferred seclusion to involuntary medication. CONCLUSION: Policy-makers who want to reduce coercive measures in psychiatry should not focus primarily on the reduction of seclusion. Patient preferences, which vary depending on the nature of the patient population, need to be considered carefully and taken into account.

Heritability of body surface temperature in hens estimated by infrared thermography at normal or hot temperatures and genetic correlations with egg and feather quality.

Exposure of laying hens to chronic heat stress results in loss of egg production. It should be possible to improve hen resilience to chronic heat stress by genetic selection but measuring their sensitivity through internal temperature is time consuming and is not very precise. In this study we used infrared thermography to measure the hen's capacity to dissipate heat, in a commercial line of laying hens subjected to cycles of neutral (N, 19.6°C) or high (H, 28.4°C) ambient temperatures. Mean body temperatures (BT) were estimated from 9355 infrared images of wing, comb and shank taken from 1200 hens. Genetic parameters were estimated separately for N and H temperatures. Correlations between BT and plumage condition were also investigated. Wing temperature had low heritability (0.00 to 0.09), consistent with the fact that wing temperature mainly reflects the environmental temperature and is not a zone of heat dissipation. The heritability of comb temperature was higher, from 0.15 to 0.19 in N and H conditions, respectively. Finally, the shank temperature provided the highest heritability estimates, with values of 0.20 to 0.22 in H and N conditions, respectively. Taken together, these results show that heat dissipation is partly under genetic control. Interestingly, the genetic correlation between plumage condition and shank and comb temperatures indicated that birds with poor condition plumage also had the possibility to dissipate heat through featherless areas. Genetic correlations of temperature measurements with egg quality showed that temperatures were correlated with egg width and weight, yolk brightness and yellowness and Haugh units only under H conditions. In contrast, shell colour was correlated with leg temperature only at thermo-neutrality.

Correlation between Doppler flow patterns in growth-restricted fetuses and neonatal circulation.

OBJECTIVES: To investigate whether prenatal Doppler parameters in growth-restricted fetuses are correlated with neonatal circulatory changes. METHODS: In 43 cases of suspected fetal growth restriction (FGR), serial Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) were performed. The last measurement, closest to delivery (< 1 week before birth), was used for analysis. Neonatal circulation was assessed for 2 h/day on Days 1-5, 8 and 15 by near-infrared spectroscopy (NIRS) of the cerebral, renal and splanchnic regions. We calculated fractional tissue oxygen extraction (FTOE) as: (arterial oxygen saturation - NIRS value)/arterial oxygen saturation. The following ratios were calculated: cerebroplacental ratio (CPR; MCA-PI/UA-PI), cerebrorenal ratio (CRR; cerebral/renal FTOE) and cerebrosplanchnic ratio (CSR; cerebral/splanchnic FTOE). Spearman's rank correlation coefficient (ρ) was calculated between prenatal Doppler parameters and neonatal NIRS variables. These analyses were carried out for the entire group, and separately for cases of early FGR (delivered < 34 weeks) and late FGR (≥ 34 weeks). RESULTS: Fetal Doppler parameters correlated with neonatal NIRS variables on Days 1-3: UA-PI correlated with renal FTOE (Day 1: ρ = 0.454, P < 0.01) and CRR (Day 1: ρ = -0.517, P < 0.001). MCA-PI correlated with cerebral FTOE on Day 2 (ρ = 0.469, P < 0.01), approached statistical significance on Day 3 but was not correlated on Day 1. CPR correlated with CRR (Day 1: ρ = 0.474, P < 0.01). Most associations lost their statistical significance when early and late FGR subgroups were considered separately. CONCLUSION: Low MCA-PI and low CPR, indicating brain sparing before birth, are associated with low CRR after birth, indicating relatively greater blood flow to the cerebrum than to the renal region. Based on the results of this study, it could be speculated that if brain sparing is present in the fetal circulation, it persists during the first 3 days after birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Large-scale investigation of the parameters in response to Eimeria maxima challenge in broilers.

Coccidiosis, a parasitic disease of the intestinal tract caused by members of the genera Eimeria and Isospora, is one of the most common and costly diseases in chicken. The aims of this study were to assess the effect of the challenge and level of variability of measured parameters in chickens during the challenge with Eimeria maxima. Furthermore, this study aimed to investigate which parameters are the most relevant indicators of the health status. Finally, the study also aimed to estimate accuracy of prediction for traits that cannot be measured on large scale (such as intestinal lesion score and fecal oocyst count) using parameters that can easily be measured on all animals. The study was performed in 2 parts: a pilot challenge on 240 animals followed by a large-scale challenge on 2,024 animals. In both experiments, animals were challenged with 50,000 Eimeria maxima oocysts at 16 d of age. In the pilot challenge, all animals were measured for BW gain, plasma coloration, hematocrit, and rectal temperature and, in addition, a subset of 48 animals was measured for oocyst count and the intestinal lesion score. All animals from the second challenge were measured for BW gain, plasma coloration, and hematocrit whereas a subset of 184 animals was measured for intestinal lesion score, fecal oocyst count, blood parameters, and plasma protein content and composition. Most of the parameters measured were significantly affected by the challenge. Lesion scores for duodenum and jejunum (P < 0.001), oocyst count (P < 0.05), plasma coloration for the optical density values between 450 and 490 nm (P < 0.001), albumin (P < 0.001), α1-globulin (P < 0.01), α2-globulin (P < 0.001), α3-globulin (P < 0.01), and ß2-globulin (P < 0.001) were the most strongly affected parameters and expressed the greatest levels of variation. Plasma protein profiles proved to be a new, reliable parameter for measuring response to Eimeria maxima. Prediction of intestinal lesion score and fecal oocyst count using the other parameters measured was not very precise (R2 < 0.7). The study was successfully performed in real raising conditions on a large scale. Finally, we observed a high variability in response to the challenge, suggesting that broilers' response to Eimeria maxima has a strong genetic determinism, which may be improved by genetic selection.

'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH ß-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V-LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.

A person-centred segmentation study in elderly care: towards efficient demand-driven care.

Providing patients with more person-centred care without increasing costs is a key challenge in healthcare. A relevant but often ignored hindrance to delivering person-centred care is that the current segmentation of the population and the associated organization of healthcare supply are based on diseases. A person-centred segmentation, i.e., based on persons' own experienced difficulties in fulfilling needs, is an elementary but often overlooked first step in developing efficient demand-driven care. This paper describes a person-centred segmentation study of elderly, a large and increasing target group confronted with heterogeneous and often interrelated difficulties in their functioning. In twenty-five diverse healthcare and welfare organizations as well as elderly associations in the Netherlands, data were collected on the difficulties in biopsychosocial functioning experienced by 2019 older adults. Data were collected between March 2010 and January 2011 and sampling took place based on their (temporarily) living conditions. Factor Mixture Model was conducted to categorize the respondents into segments with relatively similar experienced difficulties concerning their functioning. First, the analyses show that older adults can be empirically categorized into five meaningful segments: feeling vital; difficulties with psychosocial coping; physical and mobility complaints; difficulties experienced in multiple domains; and feeling extremely frail. The categorization seems robust as it was replicated in two population-based samples in the Netherlands. The segmentation's usefulness is discussed and illustrated through an evaluation of the alignment between a segment's unfulfilled biopsychosocial needs and current healthcare utilization. The set of person-centred segmentation variables provides healthcare providers the option to perform a more comprehensive first triage step than only a disease-based one. The outcomes of this first step could guide a focused and, therefore, more efficient second triage step. On a local or regional level, this person-centred segmentation provides input information to policymakers and care providers for the demand-driven allocation of resources.

Estimation and testing in targeted goup sequential covariate-adjusted randomized clinical trials.

This article is devoted to the construction and asymptotic study of adaptive group sequential covariate-adjusted randomized clinical trials analyzed through the prism of the semipara-metric methodology of targeted maximum likelihood estimation (TMLE). We show how to build, as the data accrue group-sequentially, a sampling design which targets a user-supplied optimal design. We also show how to carry out a sound TMLE statistical inference based on such an adaptive sampling scheme (therefore extending some results known in the i.i.d setting only so far), and how group-sequential testing applies on top of it. The procedure is robust (i.e., consistent even if the working model is misspecified). A simulation study confirms the theoretical results, and validates the conjecture that the procedure may also be efficient.