The association between time-series milk ß-hydroxybutyrate dynamics and early reproductive performance of dairy cows.

The DeLaval Herd Navigator is an on-farm sensor system that measures on a frequent basis milk progesterone (P4) and ß-hydroxybutyrate (BHB) in individual cows to closely monitor reproductive performance and energy balance. This information provides the opportunity to investigate the dynamics of BHB measured in milk (mBHB) and study the association between mBHB and early reproductive performance. The objectives of the study were (1) to describe mBHB dynamics within the first 20 d in milk (DIM), and (2) to evaluate the association between mBHB dynamics and early reproductive performance at cow-level. Two-year time-series data from 4,133 dairy cows in 38 Dutch dairy farms were available for analysis. Data included information on mBHB, daily milk yield and the indicators of early reproductive performance, days from calving to resumption of cyclicity, days from calving to first estrus, and days from calving to first insemination. The following mBHB dynamic parameters were defined based on the first 20 DIM for each individual cow: average mBHB (AvgBHB), DIM when mBHB was for the first time ≥80 µmol/L (OnsetKeto), the total number of consecutive days a cow had mBHB concentration ≥80 µmol/L, and the number of measurements mBHB concentration was ≥80 µmol/L. Three Cox proportional hazard regression models with random herd effect were developed to evaluate the association between cow level mBHB dynamics and days from calving to resumption of cyclicity, first estrus, and first insemination. Results showed that the mean AvgBHB within 20 DIM among all cows was 73 µmol/L. The mean OnsetKeto within 20 DIM, was 8 DIM. Among all cows having hyperketolactia, 55.8% (1,350/2,419) had OnsetKeto in the first week of lactation. In total, 41.5% (1,714/4,133) of the cows did not have OnsetKeto in the first 20 DIM. An early onset of hyperketolactia was associated with delayed fertility events. Cows with higher AvgBHB have a prolonged time interval from calving to resumption of cyclicity and first estrus. Information on mBHB dynamics and the association with early reproductive performance provides insights that might be helpful to improve reproductive performance of individual dairy cows.

SINGLE-DOSE, MULTIPLE-DOSE, AND THERAPEUTIC DRUG MONITORING PHARMACOKINETICS OF FIROCOXIB IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Firocoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID) with limited effects on COX-1, which means it likely has fewer side effects than typically associated with other NSAIDs. This study determined possible doses of firocoxib based on single- and multidose pharmacokinetic trials conducted in 10 Asian elephants (Elephas maximus). Initially, two single oral dose trials (0.01 and 0.1 mg/kg) of a commercially available tablet (n = 6) and paste (n = 4) formulation were used to determine a preferred dose. The 0.1 mg/kg dose was further evaluated via IV single dose (n = 3) and oral multidose trials (tablets n = 6; paste n = 4). Serum peak and trough firocoxib concentrations were also evaluated in Asian elephants (n = 4) that had been being treated for a minimum of 90 consecutive days. Key pharmacokinetic parameters for the 0.1 mg/kg single-dose trials included mean peak serum concentrations of 49 ± 3.3 ng/ml for tablets and 62 ± 14.8 ng/ml for paste, area under the curve (AUC) of 1,332 ± 878 h*mg/ml for tablets and 1,455 ± 634 h*mg/ml for paste, and half-life (T1/2) of 34.3 ± 30.3 h for tablets and 19.9 ± 12.8 h for paste. After 8 d of dosing at 0.1 mg/kg every 24 h, pharmacokinetic parameters stabilized to an AUC of 6,341 ± 3,003 h*mg/ml for tablets and 5,613 ± 2,262 for paste, and T1/2 of 84.4 ± 32.2 h for tablets and 62.9 ± 2.3 h for paste. Serum COX inhibition was evaluated in vitro and ex vivo in untreated elephant plasma, where firocoxib demonstrated preferential inhibition of COX-2. No adverse effects from firocoxib administration were identified in this study. Results suggest administering firocoxib to Asian elephants at a dose of 0.1 mg/kg orally, using either tablet or paste formulations, every 24 h.

Dosimetry of ultra-high dose rate electron beams using thermoluminescence and optically stimulated luminescence detectors.

Objective.The aim of this work is to investigate the dose rate dependence of thermoluminescence and optically stimulated luminescence detectors (TLDs and OSLDs) in a wide uniform ultra-high dose rate electron beam and demonstrate the potential use of TLDs and OSLDs to correct the ion recombination in air-filled ionization chambers. This study avoids previously reported complications related to the field size and homogeneity.Approach.Two types of OSLDs (BeO and Al2O3:C) and three types of TLDs (LiF:Mg,Ti, LiF:Mg,Cu,P, CaF2:Tm) were irradiated simultaneously in a uniform 16 MeV electron beam generated by a clinically decommissioned C-Arm LINAC, modified to deliver doses per pulse between 8.3 × 10-4Gy and 1.255 Gy, corresponding to instantaneous dose rates between 2 × 102Gy s-1and 3 × 105Gy s-1. A prototype ultra-thin parallel plate ionization chamber was employed as reference detector.Main results.Reproducible results were achieved both at conventional (standard deviation of the data <2%) and at the highest dose per pulse (standard deviation of the data <4%). No trend in the dose rate response of the TLDs and OSLDs was observed in the investigated dose per pulse range. The Al2O3:C OSLD was found to be the most precise detector, with a standard deviation of the data <2% at all investigated dose rates and dose levels.Significance.The dose rate independence of the investigated TLDs and OSLDs make them good candidates for dosimetry at ultra-high dose rates, at least up to 3 × 105Gy s-1. A dose rate independent method to measure the dose per pulse is proposed, which can be applied to characterize ultra-high dose rate electron beams and correct for ion recombination in ionization chambers.

Co-designing a Canadian adaptation of a lifestyle-oriented intervention aimed to improve daily functioning of individuals living with chronic pain: a multi-method study protocol of REVEAL(OT) Canada.

Background: Living with chronic pain (CP) often implies major lifestyle changes, including modifications of daily routines and work. Surprisingly, few validated and effective interventions specifically target functional outcomes in this population. Redesign your Everyday Activities and Lifestyle with Occupational Therapy [REVEAL(OT)] is a lifestyle-oriented intervention led by occupational therapists that directly targets the daily functional challenges of living with CP. The intervention was initially developed and studied as an add-on to standard treatment delivered by Danish multidisciplinary specialized pain clinics. Adapting, implementing, and evaluating REVEAL(OT) within the Canadian healthcare system will contribute to broadening the scope of treatments offered in specialized pain clinics that do not yet include occupational therapy. Objective: The proposed study aims to define and refine REVEAL(OT)/CA with partners (authors of original intervention, people with lived experience, clinicians, managers). Methods: This participatory action research will use a multi-method design and follow the ORBIT model for developing behavioral treatments for chronic diseases. A process of co-construction with partners and an advisory committee will take place in two Montreal specialized pain clinics. It consists of two related work packages (WPs). In WP1, a first series of focus groups with partners (n = 86) and workshops with the advisory committee will be conducted to co-develop the hypothetical pathway describing intervention components and their potential mechanisms of action on targeted outcomes, as well as the first version of the adapted intervention manual. WP2 will co-refine REVEAL(OT)/CA by exploring its acceptability, feasibility and mechanisms of action through intervention deliveries (at least twice in each of two specialized pain clinics; n ≥ 60 patients) and focus groups and/or individual interviews with participating patients and partners. At the end of this study, the intervention manual will be generated both in French and English. Discussion: This study will set the stage for subsequent implementation and effectiveness assessment projects and be an important step towards the deployment of interventions aiming to improve engagement in meaningful daily activities among adults living with CP. Registration: OSF Registries, osf.io/8gksa. Registered 3 August 2023, https://osf.io/8gksa.

SERUM DISPOSITION OF A SINGLE DOSE OF ORALLY ADMINISTERED FIROCOXIB IN AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

The time course of serum firocoxib concentrations was described after administration of two single oral doses (0.01 and 0.1 mg/kg) of commercially available firocoxib tablet (n = 4) and paste (n = 2) formulations to six healthy adult female African (Loxodonta africana) elephants. Firocoxib was quantitated by high-performance liquid chromatography. Firocoxib serum concentrations were below detectable levels after administration of 0.01 mg/kg of both formulations. A dose of 0.1 mg/kg (n = 4) of the tablet formulation had the following mean ± SD of pharmacokinetic parameters: area under the curve (AUC) 1,588 ± 362 h × ng/ml, maximum plasma concentration (Cmax) 31 ± 6.6 ng/ml at 6.4 ± 1.8 h, and disappearance half-life (T1/2) 66 ± 59 h, Elephant compliance to oral administration of the paste formulation was challenging, with only two elephants accepting administration of the paste at 0.1 mg/kg. Pharmacokinetic parameters determined included AUC of 814 h × ng/ml, Cmax of 44 ng/ml at Tmax of 7.0 h, and T1/2 of 36.4 h. Based on mean AUC, the relative bioavailability of paste compared to tablet formulations was 50%. Limitations of this study were the small number of participants and elephant compliance with the paste formulation. This study supports an oral dose of 0.1 mg/kg every 24 h. Multidose and IV trials are indicated to confirm firocoxib dosing requirements for African elephants.

NfL and GFAP in serum are associated with microstructural brain damage in progressive multiple sclerosis.

BACKGROUND: The potential of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of disease activity and severity in progressive forms of multiple sclerosis (MS) is unclear. OBJECTIVE: To investigate the relationship between serum concentrations of NfL, GFAP, and magnetic resonance imaging (MRI) in progressive MS. METHODS: Serum concentrations of NfL and GFAP were measured in 32 healthy controls and 32 patients with progressive MS from whom clinical and MRI data including diffusion tensor imaging (DTI) were obtained during three years of follow-up. RESULTS: Serum concentrations of NfL and GFAP at follow-up were higher in progressive MS patients than in healthy controls and serum NfL correlated with the EDSS score. Decreasing fractional anisotropy (FA) in normal-appearing white matter (NAWM) correlated with worsening EDSS scores and higher serum NfL. Higher serum NfL and increasing T2 lesion volume correlated with worsening paced autitory serial addition test scores. In multivariable regression analyses with serum GFAP and NfL as independent factors and DTI measures of NAWM as dependent factors, we showed that high serum NfL at follow-up was independently associated with decreasing FA and increasing MD in NAWM. Moreover, we found that high serum GFAP was independently associated with decreasing MD in NAWM and with decreasing MD and increasing FA in cortical gray matter. CONCLUSION: Serum concentrations of NfL and GFAP are increased in progressive MS and are associated with distinct microstructural changes in NAWM and CGM.

Secondary amputation after lower extremity free-flap reconstruction.

BACKGROUND: Microsurgical free-tissue transfer is often the definitive reconstructive option for lower extremity limb salvage. Despite an initial successful free-flap reconstruction, some patients ultimately undergo lower extremity amputation. The indications for secondary amputation include non- or malunion, infection, hardware failure, or chronic pain. This study aimed to identify the etiology and outcome of secondary amputation after lower extremity free-flap reconstruction. METHODS: A retrospective cohort study was performed including patients who underwent lower extremity free-flap reconstruction from January 2002 to December 2020. Patients who underwent secondary amputation were identified. A survey based on the PROMIS® Pain Interference Scale and activities of daily living (ADLs) was then conducted to assess patient-reported outcomes. Fifteen (52%) patients who underwent amputation responded to the survey, with a median follow-up time of 4.4 years. RESULTS: Of 410 patients who underwent lower extremity free-flap reconstruction, 40 (9.8%) patients underwent subsequent amputation. Of these, 10 patients had failed free-flap reconstruction and 30 patients had secondary amputation after an initially successful soft tissue coverage. The most common etiology for secondary amputation was infection (68%, n = 27). Eighty percent (n = 12) of survey respondents were able to use a prosthetic limb and ambulate. CONCLUSIONS: The most common etiology of secondary amputation was infection. Most patients who ultimately underwent amputation were able to ambulate with a prosthetic, but the majority of patients reported chronic pain. This study could be used to guide potential free-flap candidates regarding the risks and outcomes of lower extremity free-flap reconstruction.

Investigation of TL and OSL detectors in ultra-high dose rate electron beams.

Objective.This work aims at investigating the response of various thermally stimulated luminescence detectors (TLDs) and optically stimulated luminescence detectors (OSLDs) for dosimetry of ultra-high dose rate electron beams. The study was driven by the challenges of dosimetry at ultra-high dose rates and the importance of dosimetry for FLASH radiotherapy and radiobiology experiments.Approach.Three types of TLDs (LiF:Mg,Ti; LiF:Mg,Cu,P; CaF2:Tm) and one type of OSLD (Al2O3:C) were irradiated in a 15 MeV electron beam with instantaneous dose rates in the (1-324) kGy s-1range. Reference dosimetry was carried out with an integrating current transformer, which was calibrated in absorbed dose to water against a reference ionization chamber. Additionally, dose rate independent BeO OSLDs were employed as a reference. Beam non-uniformity was addressed using a matrix of TLDs/OSLDs.Main results.The investigated TLDs were shown to be dose rate independent within the experimental uncertainties, which take into account the uncertainty of the dosimetry protocol and the irradiation uncertainty. The relative deviation between the TLDs and the reference dose was lower than 4 % for all dose rates. A decreasing response with the dose rate was observed for Al2O3:C OSLDs, but still within 10 % from the reference dose.Significance.The precision of the investigated luminescence detectors make them suitable for dosimetry of ultra-high dose rate electron beams. Specifically, the dose rate independence of the TLDs can support the investigation of the beam uniformity as a function of the dose rate, which is one of the challenges of the employed beam. Al2O3:C OSLDs provided high precision measurements, but the decreasing response with the dose rate needs to be confirmed by additional experiments.

Occupational balance as a component in weight loss interventions.

BACKGROUND: Obesity can limit occupational participation because of physical and mental barriers. Weight loss programmes emphasizing dietary and physical activity may lower body weight; however, mental barriers and sustainable weight loss seemed to be challenged. Weight loss influences daily patterns and structure of occupations and finding a balance in daily life during the weight loss process might improve sustainable weight loss. AIM: To explore if and how health professionals conducting weight loss programmes in Danish municipalities address elements related to occupational balance in the daily life of citizens with obesity. MATERIAL AND METHODS: Twenty individual interviews with health professionals from Danish municipalities were conducted and analysed. RESULTS: (1) Helping participants find the time and energy to lose weight, (2) Emphasizing small steps for sustainable changes and (3) Utilizing the citizen's life experience for direction. CONCLUSION: Elements of occupational balance might be addressed by the participants, however values and meaningfulness regarding occupations seem to be missing. Integrating occupational balance in weight loss programmes could enable health professionals to understand and address sustainable weight loss. SIGNIFICANCE: Occupational therapists may be ideally suited to support citizens with obesity to sustain weight loss by supporting a balanced life focussing on meaningfulness and values in occupations.

Validation of the type 1 diabetes distress scale (T1-DDS) in a large Danish cohort: Content validation and psychometric properties.

Aim: To validate the Type 1 Diabetes Distress Scale (T1-DDS) in a large sample of adults with Type 1 diabetes (T1D) from diabetes clinics in Denmark. Methods: Altogether 40 adults with T1D were interviewed to explore the content of T1-DDS in a Danish setting and to validate the translation of the T1-DDS into Danish. Subsequently, a survey including T1-DDS, the Problem Areas In Diabetes scale (PAID-20), fear of hypoglycemia, social support, and diabetes duration was answered by 2201 people with T1D. Other person characteristics were collected from the National Patient Register. HbA1c was obtained from the Clinical Laboratory Information System. Data distribution, internal consistency, convergent and construct validity, factor structure, three weeks retest, and cut-points were explored. Results: Interview data supported the relevance of all T1-DDS items for the assessment of diabetes distress among adults with T1D. The T1-DDS showed good content and acceptable construct validity, and the ability to detect high diabetes distress levels. A high correlation between T1-DDS and PAID-20 (rho = 0.91) was found. The retest scores showed a good reliability (all rho ≥0.68) with the highest variability in the Friends/Family Distress and Physician Distress subscales and the lowest variability in the Powerlessness and Eating Distress subscales of the T1-DDS. Qualitative findings pointed out relevant concerns of people with T1D, which were not included in the T1-DDS. Conclusion: The study supports the use of the Danish T1-DDS, but also highlights that existing diabetes distress questionnaires including T1-DDS do not cover all potential diabetes stressors and worries.

Using a digital platform to establish odontometric variation based on race, gender and Angle classification.

Orthodontists often encounter significant clinical challenges in the finishing stages of treatment due to a disproportion in interarch tooth size relationships. Despite the increasing presence of digital technology and concomitant focus on customized treatment approaches, there is a gap in the knowledge of how generating tooth size data using digital versus traditional methods may impact our treatment regime. OBJECTIVE: This study aimed to compare the prevalence of tooth size discrepancies using digital models and a digitally based cast analysis in our cohort based on (i) Angle's Classification; (ii) gender and (iii) race. MATERIALS AND METHODS: The mesiodistal widths of teeth in 101 digital models were assessed using computerized odontometric software. A Chi-square test was used to determine the prevalence of tooth size disproportions among the study groups. The differences between all three groups of the cohort were analysed using a three-way analysis of variance (ANOVA). RESULTS: An overall Bolton tooth size discrepancy (TSD) prevalence of 36.6% was observed in our study cohort; 26.7% had an anterior Bolton TSD. No differences existed in the prevalence of tooth size discrepancies between male and female subjects as well as between the different malocclusion groups (P > .05). Caucasian subjects had a statistically significant smaller prevalence of TSD compared to Black and Hispanic patients (P < .05). CONCLUSION: The prevalence results in this study illuminate how relatively common TSD is and underscores the importance of proper diagnosis. Our findings also suggest that racial background may be an influential factor in the presence of TSD.

Characterization of LiF:Mg,Ti thermoluminescence detectors in low-LET proton beams at ultra-high dose rates.

Objective.This work aims at characterizing LiF:Mg,Ti thermoluminescence detectors (TLDs) for dosimetry of a 250 MeV proton beam delivered at ultra-high dose rates (UHDR). Possible dose rate effects in LiF:Mg,Ti, as well as its usability for dosimetry of narrow proton beams are investigated.Approach.LiF:Mg,Ti (TLD-100TMMicrocubes, 1 mm × 1 mm × 1 mm) was packaged in matrices of 5 × 5 detectors. The center of each matrix was irradiated with single-spot low-LET (energy >244 MeV) proton beam in the (1-4500) Gy s-1average dose rates range. A beam reconstruction procedure was applied to the detectors irradiated at the highest dose rate (Gaussian beam sigma <2 mm) to correct for volumetric averaging effects. Reference dosimetry was carried out with a diamond detector and radiochromic films. The delivered number of protons was measured by a Faraday cup, which was employed to normalize the detector responses.Main results.The lateral beam spread obtained from the beam reconstruction agreed with the one derived from the radiochromic film measurements. No dose rates effects were observed in LiF:Mg,Ti for the investigated dose rates within 3% (k= 1). On average, the dose response of the TLDs agreed with the reference detectors within their uncertainties. The largest deviation (-5%) was measured at 4500 Gy s-1.Significance.The dose rate independence of LiF:Mg,Ti TLDs makes them suitable for dosimetry of UHDR proton beams. Additionally, the combination of a matrix of TLDs and the beam reconstruction can be applied to determine the beam profile of narrow proton beams.

Nanoscopy and an extended lateral approach can improve the management of latero-central segments in tibial plateau fractures: a cadaveric study.

INTRODUCTION: The objective of this investigation was to compare different techniques to improve visualization and reduction in tibial plateau fractures involving the central lateral segments. METHODS: Matched pairs of pre-fractured cadaveric tibial plateau fractures that include the central lateral segments were treated by either an anterolateral approach (supine) or PL approach (prone). Reduction was stepwise extended by additional fracturoscopy (FS), nanoscopy (NS) and lastly by epicondyle osteotomy (ECO). Reduction was analyzed by 3D scan and visualization of the lateral plateau was quantified. RESULTS: Ten specimens (3 pairs 41B3.1, 2 pairs 41C3.3) were analyzed. Fracture steps involving the antero-latero-central (ALC) segment were insufficiently reduced after fluoroscopy using both approaches (AL 2.2 ± 1.2 mm vs PL 2.2 ± 1.0 mm, p 0.95). Additional NS and ECO achieved optimized fracture reduction in the ALC segment (NS AL 1.6 ± 1.3 mm vs PL 0.8 ± 0.9 mm, p 0.32). NS provided visualization of the entire lateral plateau (PL 102.9% ± 7.4, AL 108.8 ± 19.2%), while fracturoscopy only allowed visualization of the ALL segment and partially of PLL and ALC segments (PL 22.0 ± 23.4%, AL 29.7 ± 18.3%). CONCLUSION: Optimized reduction of tibial head fractures with involvement of latero-central segments requires additional video-assisted reduction or extended approaches. Nanoscopy helps visualizing of the entire lateral plateau, when compared to fracturoscopy and may become a valuable reduction aid.

Morphological alterations of the abdominal wall after open incisional hernia repair with endoscopic anterior and open posterior component separation.

PURPOSE: Effects of component separation (CS) on abdominal wall morphology have only been investigated in smaller case series or cadavers. This study aimed to compare abdominal wall alterations following endoscopic anterior CS (EACS) or open transverse abdominis release (TAR). METHODS: Computed tomography scans were evaluated in patients who had undergone open incisional hernia repair with EACS or TAR. Abdominal wall circumference, lateral abdominal wall muscle thickness, and displacement were compared with (1) preoperative images after bilateral CS and (2) the undivided side postoperatively after unilateral CS. RESULTS: In total, 105 patients were included. Fifty-five (52%) and 15 (14%) underwent bilateral and unilateral EACS, respectively. Five (5%) and 14 (13%) underwent bilateral and unilateral TAR, respectively. Sixteen (15%) underwent unilateral EACS and contralateral TAR. The external oblique and transverse abdominis muscles were significantly laterally displaced with a mean of 2.74 cm (95% CI 2.29-3.19 cm, P < 0.001) and 0.82 cm (0.07-1.57 cm, P = 0.032) after EACS and TAR, respectively. The combined thickness of the lateral muscles was significantly decreased after EACS (mean decrease 10.5% (5.8-15.6%, P < 0.001)) and insignificantly decreased after TAR (mean decrease 2.6% (- 4.8 to 9.5%, P = 0.50)). The abdominal wall circumference was unchanged after bilateral (mean reduction 0.90 cm (- 0.77 to 2.58 cm), P = 0.29) and unilateral CS (mean increase 0.03 cm (- 1.01 to 1.08 cm), P = 0.95). CONCLUSION: Postoperative changes in the lateral abdominal wall musculature were different following EACS and open TAR. Either technique seems not to compromise the overall integrity of the lateral abdominal wall.

Ultra-high dose rate dosimetry for pre-clinical experiments with mm-small proton fields.

PURPOSE: To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams. METHODS: At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of âˆ¼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference. RESULTS: The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, Al2O3:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively. CONCLUSIONS: Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s.

The relationships between early lactation energy status indicators and endocrine fertility traits in dairy cows.

The relationships between dairy cow milk-based energy status (ES) indicators and fertility traits were studied during periods 8 to 21, 22 to 35, 36 to 49, and 50 to 63 d in milk. Commencement of luteal activity (C-LA) and interval from calving to the first heat (CFH), based on frequent measurements of progesterone by the management tool Herd Navigator (DeLaval), were used as fertility traits. Energy status indicator traits were milk ß-hydroxybutyrate (BHB) concentration provided by Herd Navigator and milk fat:protein ratio, concentration of C18:1 cis-9, the ratio of fatty acids (FA) C18:1 cis-9 and C10:0 in test-day milk samples, and predicted plasma concentration of nonesterified fatty acids (NEFA) on test days. Plasma NEFA predictions were based either directly on milk mid-infrared spectra (MIR) or on milk fatty acids based on MIR spectra (NEFAmir and NEFAfa, respectively). The average (standard deviation) C-LA was 39.3 (±16.6) days, and the average CFH was 50.7 (±17.2) days. The correlations between fertility traits and ES indicators tended to be higher for multiparous (r < 0.28) than for primiparous (r < 0.16) cows. All correlations were lower in the last period than in the other periods. In period 1, correlations of C-LA with NEFAfa and BHB, respectively, were 0.15 and 0.14 for primiparous and 0.26 and 0.22 for multiparous cows. The associations between fertility traits and ES indicators indicated that negative ES during the first weeks postpartum may delay the onset of luteal activity. Milk FPR was not as good an indicator for cow ES as other indicators. According to these findings, predictions of plasma NEFA and milk FA based on milk MIR spectra of routine test-day samples and the frequent measurement of milk BHB by Herd Navigator gave equally good predictions of cow ES during the first weeks of lactation. Our results indicate that routinely measured milk traits can be used for ES evaluation in early lactation.

Prevalence of comorbidities, and affective disorders in epilepsy: A latent class analysis approach.

OBJECTIVE: Epilepsies are severe chronic neurological diseases that impair several domains in life and are often accompanied by various somatic and psychiatric comorbidities. Associations between epilepsy and its comorbidities remain poorly understood. As epidemiological research mainly relies on cross-sectional designs and descriptive results, homogeneities regarding comorbidities in individuals suffering from epilepsy remain uncovered. Therefore, we aimed to identify clusters of individuals based on selected seizure-related variables and somatic comorbidities, and their respective risk of experiencing affective disorders, using a Latent Class Analysis (LCA). METHODS: Latent class analysis, is a model-driven statistical approach, which aims at latent, unobservable clusters on selected disease features. LCA has therefore the potential for uncovering previously unobservable groups or classes with similar comorbidity patterns. It allows for comparisons between those classes regarding risk or promotive factors - such as affective disorders. Our data derives from the Austrian cohort of the European Study on Burden and Care of Epilepsy (ESBACE; http://www.esbace.eu/). In ESBACE, multiple factors were collected to get a detailed picture on prevalence, epilepsy-related variables and comorbidities in a population-based cohort from the region of Salzburg, Austria. We used LCA to identify epilepsy-somatic-comorbidity-clusters and further, compared them to the observed the risk of suffering from affective disorders. RESULTS: The prevalence of epilepsy in the study region was 9.14/1000 inhabitants. LCA unveiled a three-cluster solution, of which one cluster, mainly consisting of individuals with mixed seizure types, higher age, and discrete somatic comorbidities (stroke, cardiovascular - and respiratory/pulmonary diseases) had a higher risk of experiencing affective disorders. SIGNIFICANCE: To our knowledge, this is the first large scale study that uses LCA to identify epilepsy-related comorbidity phenotypes, and therefore it might open a new way for epidemiological research.

NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients.

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Visceral obesity is a predictor of surgical site occurrence and hernia recurrence after open abdominal wall reconstruction.

PURPOSE: High body mass index (BMI) increases the risk of postoperative complications and hernia recurrence after abdominal wall reconstruction (AWR). However, BMI does not provide specific information on the mass and distribution of adipose tissue. We hypothesized that visceral fat volume (VFV) was a better predictor than BMI for recurrence after AWR. METHODS: We included all patients undergoing AWR at our institution from November 2010 to December 2016. Data were collected from a prospective database and all patients were summoned for follow-up. VFV was calculated from preoperative CT. The primary and secondary outcomes were hernia recurrence and 30-day postoperative surgical site occurrences (SSO), respectively. RESULTS: We included a total of 154 patients. At follow-up, 42 (27.3%) patients had developed recurrence. The recurrence rate was significantly higher in patients with a VFV higher than the mean compared to a VFV lower than the mean, P = 0.004. After multivariable Cox-regression, VFV remained significantly predictive of recurrence (HR 1.09 per 0.5 L increase of VFV, P = 0.018). In contrary, BMI was not associated with hernia recurrence. There was no significant difference in the rate of SSO between patients with a VFV above and below the mean. A multivariable logistic regression model showed that VFV was significantly associated with development of SSO (OR 1.12 per 0.5 L increase, P = 0.009). CONCLUSION: VFV was significantly associated with recurrence and SSOs after AWR. This study suggests VFV as a risk assessment tool for patients undergoing AWR.