Photonic Source of Heralded Greenberger-Horne-Zeilinger States.

Generating large multiphoton entangled states is of main interest due to enabling universal photonic quantum computing and all-optical quantum repeater nodes. These applications exploit measurement-based quantum computation using cluster states. Remarkably, it was shown that photonic cluster states of arbitrary size can be generated by using feasible heralded linear optics fusion gates that act on heralded three-photon Greenberger-Horne-Zeilinger (GHZ) states as the initial resource state. Thus, the capability of generating heralded GHZ states is of great importance for scaling up photonic quantum computing. Here, we experimentally demonstrate this required building block by reporting a polarisation-encoded heralded GHZ state of three photons, for which we build a high-rate six-photon source (547±2 Hz) from a solid-state quantum emitter and a stable polarization-based interferometer. The detection of three ancillary photons heralds the generation of three-photon GHZ states among the remaining particles with fidelities up to F=0.7278±0.0106. Our results initiate a path for scalable entangling operations using heralded linear-optics implementations.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Lactation curves of Montbéliarde-sired and Viking Red-sired crossbred cows and their Holstein herdmates in commercial dairies.

Lactation curves were estimated for Montbéliarde (MO) × Holstein (HO) and Viking Red (VR) × HO 2-breed crossbred cows and for MO × VR/HO and VR × MO/HO 3-breed crossbred cows and their HO herdmates from test-day observations in 7 high-performance herds that participated in a designed study. Cows calved from 2010 to 2017. Test-day observations from milk recording were used to fit the lactation curves of cows in their first 3 lactations. Lactations of cows were required to have at least 250 DIM and to have at least 6 test days ≤265 DIM. Lactation curves from random regression (RR) were compared for 305-d production (kg), peak production (kg), peak day of production, and production from 4 to 103 DIM (kg), from 104 to 205 DIM (kg), and from 206 to 305 DIM (kg) for milk, fat, and protein. Also, the persistency of production was compared. First-lactation versus second- and third-lactation cows were analyzed separately for both the 2-breed and 3-breed crossbred cows and their respective HO herdmates. Legendre polynomial RR had the best goodness of fit for the lactation curves compared with Ali-Schaeffer and Wilmink RR from the test-day observations of milk, fat, and protein production. For fluid milk production of first-lactation cows, the MO × HO 2-breed crossbreds were not different from their HO herdmates for any of the lactation-curve characteristics, except persistency. However, the VR × HO 2-breed crossbreds had less fluid milk production compared with their HO herdmates. For first lactation, the MO × HO 2-breed crossbreds had more persistency of milk, fat, and protein production compared with their HO herdmates. The first-lactation MO × VR/HO 3-breed crossbreds had more persistency of fluid milk production compared with their HO herdmates. For second and third lactations, both the MO × HO and the VR × HO 2-breed crossbreds had higher fat production compared with their HO herdmates. Furthermore, the MO × HO 2-breed crossbreds had more protein production (kg) in all 3 periods of lactation compared with their HO herdmates. Crossbred cows may have advantages over HO cows for persistency of production in high-performance herds.

Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Measuring ß-galactosidase activity in opaque dairy solutions under optimum conditions for galactooligosaccharide synthesis by isothermal titration calorimetry.

The dairy industry uses enzymes to make cheese, alter product flavor, and eliminate lactose. The activities of these enzymes have been measured in clear buffered solutions, but because of the limitations of spectrophotometric methods, enzyme activities have not been measured in opaque or colored dairy products where they are used. Isothermal titration calorimetry (ITC) can be used to determine reaction kinetics in opaque and colored solutions by measuring the heat rate (thermal power) from enzyme-catalyzed reactions as a function of time. This study used ITC to measure ß-galactosidase activity in opaque solutions of milk, sweet whey, sweet whey permeate, acid whey, and acid whey permeate with 2 ß-galactosidase (Enzyme Commission number 3.2.1.23) isozymes derived from Aspergillus oryzae and Kluyveromyces lactis. The components of the dairy fluids alter the enzyme kinetics and reaction thermodynamics, and the reactions catalyzed by the 2 homologues differ as shown by differing thermodynamic profiles. The study demonstrates that ITC can be used to measure enzyme activity in opaque and colored dairy fluids and identify reactions by their thermodynamic properties.

Birth traits of Holstein calves compared with Holstein, Jersey, Montbéliarde, Normande, and Viking Red-sired crossbred calves.

Holstein (HO) calves, 3-breed crossbred calves of Montbéliarde, Viking Red, and HO (MVH), and 3-breed crossbred calves of Normande, Jersey, and Viking Red (NJV) were compared for gestation length (GL), calf weight at birth (CW), calving difficulty (CD), and stillbirth (SB) in 2 research herds at the University of Minnesota. Calves were born from January 2009 to December 2019. For the St. Paul and Morris herds, HO calves (n = 1,121) were compared with MVH calves (n = 1,393) from primiparous and multiparous cows. For the single herd analysis at Morris, HO calves (n = 476), MVH calves (n = 922), and NJV calves (n = 405) were compared from primiparous and multiparous cows. Primiparous and multiparous births were analyzed separately because multiparous cows had multiple births, and CD and SB are likely different traits for primiparous and multiparous cows. Statistical analysis of GL, CW, CD, and SB included fixed effects of sex of calf, herd, breed group of calf, and year-season of calving. For the St. Paul and Morris herds, HO calves from primiparous (278 d) and multiparous (279 d) HO cows had shorter GL compared with MVH calves from primiparous (280 d) and multiparous (282 d) crossbred cows. The HO calves (39.4 and 43.2 kg, respectively) from primiparous and multiparous HO cows had lower CW compared with MVH calves (40.3 and 44.3 kg, respectively) from primiparous and multiparous crossbred cows. Calving difficulty and SB were not different for HO and MVH calves from primiparous and multiparous cows. For the single herd analysis at Morris, HO calves (278 and 279 d, respectively) from primiparous and multiparous HO cows had shorter GL compared with MVH calves (281 and 282 d, respectively) and NJV calves (282 and 282 d, respectively) from primiparous and multiparous crossbred cows. The CW of HO calves (38.6 and 42.0 kg, respectively) from primiparous and multiparous HO cows was lower compared with MVH calves (39.7 and 42.9 kg, respectively), but higher compared with NJV calves (35.1 and 38.0 kg, respectively) from primiparous and multiparous crossbred cows. Calving difficulty and SB did not differ for HO, MVH, and NJV calves from primiparous and multiparous cows. The longer GL for crossbred calves and higher CW for MVH calves did not increase CD and SB for primiparous and multiparous cows. Dairy producers may implement 3-breed rotational crossbreeding systems that include the HO, Jersey, Normande, Montbéliarde, and Viking Red breeds, and some breeds may increase GL and CW without an increase in CD and SB.

Comparison of 3-breed rotational crossbreds of Montbéliarde, Viking Red, and Holstein with Holstein cows fed 2 alternative diets for dry matter intake, production, and residual feed intake.

The objective of this study was to compare 3-breed rotational crossbred (CB) cows of the Montbéliarde, Viking Red, and Holstein (HO) breeds with HO cows fed 2 alternative diets for dry matter intake (DMI), fat plus protein production (CFP), body weight (BW), body condition score (BCS), feed efficiency, and residual feed intake (RFI) from 46 to 150 days in milk (DIM) during first lactation. The CB cows (n = 17) and HO cows (n = 19) calved from September 2019 to March 2020. Cows were fed either a traditional total mixed ration diet (TRAD) or a higher fiber, lower starch total mixed ration diet (HFLS). The HFLS had 21% more corn silage, 47% more alfalfa hay, 44% less corn grain, and 43% less corn gluten feed than the TRAD. The 2 diets were analyzed for dry matter content, crude protein, forage digestibility, starch, and net energy for lactation. The BW and BCS were recorded once weekly. Daily milk, fat, and protein production were estimated from twice monthly milk recording with random regression. Measures of efficiency were CFP per kilogram of DMI and DMI per kilogram of BW. The RFI from 46 to 150 DIM was the residual error from regression of DMI on milk energy, metabolic BW, and the energy required for change in BW. Statistical analysis of all variables included the fixed effects of diet, breed group, and the interaction of diet and breed group. The CB cows fed HFLS had less DMI (-12%) and lower DMI/BW (-14%) compared with the HO cows fed TRAD. For CFP, CB and HO cows were not different when fed TRAD or HFLS. Furthermore, the CB cows fed HFLS had higher BW (+50 kg) compared with HO cows fed HFLS. The CB cows fed TRAD had higher BCS than HO cows fed TRAD and HO cows fed HFLS (+0.46 and +0.62, respectively). The HO cows fed TRAD had more DMI (+14%) and lower CFP per kilogram of DMI (-12%) compared with the HO cows fed HFLS. In addition, mean RFI from 46 to 150 DIM was lower and more desirable for CB cows fed HFLS (-120.0 kg) compared with HO cows fed TRAD (85.3 kg). Dairy producers may feed either TRAD or HFLS to CB cows without loss of CFP.

AI-Based Protein Interaction Screening and Identification (AISID).

In this study, we presented an AISID method extending AlphaFold-Multimer's success in structure prediction towards identifying specific protein interactions with an optimized AISIDscore. The method was tested to identify the binding proteins in 18 human TNFSF (Tumor Necrosis Factor superfamily) members for each of 27 human TNFRSF (TNF receptor superfamily) members. For each TNFRSF member, we ranked the AISIDscore among the 18 TNFSF members. The correct pairing resulted in the highest AISIDscore for 13 out of 24 TNFRSF members which have known interactions with TNFSF members. Out of the 33 correct pairing between TNFSF and TNFRSF members, 28 pairs could be found in the top five (including 25 pairs in the top three) seats in the AISIDscore ranking. Surprisingly, the specific interactions between TNFSF10 (TNF-related apoptosis-inducing ligand, TRAIL) and its decoy receptors DcR1 and DcR2 gave the highest AISIDscore in the list, while the structures of DcR1 and DcR2 are unknown. The data strongly suggests that AlphaFold-Multimer might be a useful computational screening tool to find novel specific protein bindings. This AISID method may have broad applications in protein biochemistry, extending the application of AlphaFold far beyond structure predictions.

COVID-19 symptoms: a case-control study, Portugal, March-April 2020.

COVID-19, although a respiratory illness, has been clinically associated with non-respiratory symptoms. We conducted a negative case-control study to identify the symptoms associated with SARS-CoV-2-positive results in Portugal. Twelve symptoms and signs included in the clinical notification of COVID-19 were selected as predictors, and the dependent variable was the RT-PCR test result. The χ2 tests were used to compare notified cases on sex, age group, health region and presence of comorbidities. The best-fit prediction model was selected using a backward stepwise method with an unconditional logistic regression. General and gastrointestinal symptoms were strongly associated with a positive test (P < 0.001). In this sense, the inclusion of general symptoms such as myalgia, headache and fatigue, as well as diarrhoea, together with actual clinical criteria for suspected cases, already updated and included in COVID-19 case definition, can lead to increased identification of cases and represent an effective strength for transmission control.

Epidemiology and transmission characteristics of early COVID-19 cases, 20 January-19 March 2020, in Bavaria, Germany.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) led to a significant disease burden and disruptions in health systems. We describe the epidemiology and transmission characteristics of early coronavirus disease 2019 (COVID-19) cases in Bavaria, Germany. Cases were reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections, reported from 20 January-19 March 2020. The incubation period was estimated using travel history and date of symptom onset. To estimate the serial interval, we identified pairs of index and secondary cases. By 19 March, 3546 cases were reported. A large proportion was exposed abroad (38%), causing further local transmission. Median incubation period of 256 cases with exposure abroad was 3.8 days (95%CI: 3.5-4.2). For 95% of infected individuals, symptom onset occurred within 10.3 days (95%CI: 9.1-11.8) after exposure. The median serial interval, using 53 pairs, was 3.5 days (95%CI: 3.0-4.2; mean: 3.9, s.d.: 2.2). Travellers returning to Germany had an important influence on the spread of SARS-CoV-2 infections in Bavaria in early 2020. Especially in times of low incidence, public health agencies should identify holiday destinations, and areas with ongoing local transmission, to monitor potential importation of SARS-CoV-2 infections. Travellers returning from areas with ongoing community transmission should be advised to quarantine to prevent re-introductions of COVID-19.

Herd life, lifetime production, and profitability of Viking Red-sired and Montbéliarde-sired crossbred cows compared with their Holstein herdmates.

The first 2 generations from a 3-breed rotation of the Viking Red (VR), Montbéliarde (MO), and Holstein (HO) breeds were compared with their HO herdmates in high-performance commercial herds in Minnesota. The designed study enrolled pure HO females in 2008 to initiate a comparison of 3-breed rotational crossbreds with their HO herdmates. Sires of cows were proven artificial insemination bulls selected for high genetic merit in each of the 3 breeds. The first-generation cows calved for a first time from 2010 to 2014 and had 376 VR × HO and 358 MO × HO crossbreds to compare with their 640 HO herdmates. The second-generation cows calved for a first time from 2012 to 2014 and had 109 VR × MO/HO and 117 MO × VR/HO crossbreds to compare with their 250 HO herdmates. Collection of data ceased on December 31, 2017, and all cows studied had the opportunity for 45 mo in the herd after first calving. Production of milk, fat, and protein (kg) during lifetimes of cows was estimated from test-day observations with best prediction. The lifetime profit function included revenue and cost. Revenue was from production, calves, and slaughter of cull cows. Costs included feed cost during lactation, lactating overhead cost, dry cow cost (including feed cost during dry periods), replacement cost, health treatment cost, insemination cost, fertility hormone cost, pregnancy diagnosis cost, hoof trimming cost, and carcass disposal cost. For individual cows with herd life longer than 45 mo after first calving, survival of cows was projected beyond 45 mo after first calving to estimate herd life, production, and profitability. The 2-breed crossbreds had +158 d longer herd life and the 3-breed crossbreds had +147 d longer herd life compared with their respective HO herdmates. Also, 12.4% of the 2-breed crossbreds died up to 45 mo after first calving compared with 16.3% of their HO herdmates. Furthermore, approximately 29% of both the 2-breed and 3-breed crossbreds lived beyond 45 mo after first calving compared with approximately 18% of their respective HO herdmates. On a lifetime basis, the 2-breed and 3-breed crossbreds provided +$122 and +$134, respectively, more cull cow revenue compared with their HO herdmates. For lifetime replacement cost, the 2-breed crossbreds did not differ from their HO herdmates; however, the 3-breed crossbreds had -$28 less lifetime replacement cost compared with their HO herdmates because of their younger age at first calving. The combined 2-breed crossbreds had +$0.473 (+13%) more daily profit (ignoring potential differences for feed efficiency) and the combined 3-breed crossbreds had +$0.342 (+9%) more daily profit compared with their respective HO herdmates. This resulted in +$173 more profit/cow annually for the combined 2-breed crossbreds and +$125 more profit/cow annually for the combined 3-breed crossbreds compared with their respective HO herdmates.

Pre-clinical evaluation of the effect of co-medication with antibiotics and oral steroids in Göttingen Minipigs on the biological activity of the probiotic medicinal product TSO (Trichuris suis ova).

The probiotic medicinal product TSO (Trichuris suis ova) is administered to patients with active ulcerative colitis in an ongoing clinical phase IIb trial where the typical co-medications are steroids (prednisolone or budesonide) and antibiotics (e.g., phenoxymethylpenicillin). The present pre-clinical study evaluates the effects of these co-medications on the biological activity of TSO in Göttingen Minipigs. This translationally relevant pre-clinical model allows administration of TSO with and without oral steroids or antibiotics in a manner similar to the administration to patients, followed by quantification of the biological activity of TSO. The biological activity of TSO was not affected by oral steroids but was reduced by oral antibiotics. Fecal calprotectin, the common marker of intestinal inflammation in patients with UC, did not differ between groups.

Health treatment cost, stillbirth, survival, and conformation of Viking Red-, Montbéliarde-, and Holstein-sired crossbred cows compared with pure Holstein cows during their first 3 lactations.

Three generations of crossbreds from a 3-breed rotation of the Viking Red (VR), Montbéliarde (MO), and Holstein (HO) breeds were compared with their HO herdmates in 7 commercial dairy herds in Minnesota. The designed study enrolled 3,550 HO females in 2008 to initiate crossbreeding and a control of pure HO herdmates within each herd. Service sires were high-ranking, proven AI bulls selected for high genetic merit within each of the VR, MO, and HO breeds. Cows in this study calved from 2010 to 2017 and collection of data ended on December 31, 2017. The first generation of cows consisted of 644 VR × HO and 616 MO × HO crossbreds and their 1,405 HO herdmates. The second generation had 615 VR × MO/HO and 568 MO × VR/HO crossbreds and their 1,462 HO herdmates. The third generation had 466 combined HO × VR/MO/HO and HO × MO/VR/HO crossbreds and their 736 HO herdmates. Total health cost was the sum of veterinary treatment cost, pharmaceutical cost, and farm labor cost to treat 16 different health disorders. Conformation traits and body condition score were subjectively scored once during early lactation for each of the first 3 lactations of cows. Total health cost of the 2-breed crossbreds was significantly lower during first (-23%), second (-29%), and third (-21%) lactation compared with their HO herdmates. For the 3-breed crossbreds, total health cost did not differ during first lactation but was -26% lower during both second and third lactation compared with their HO herdmates. The stillbirth rate for calves born to 2-breed crossbred dams (4%) was significantly lower compared with calves born to their HO herdmates (8%) at first calving. Survival from first to third calving (+9%) and first to fourth calving (+11%) was significantly higher for the 2-breed crossbreds compared with their HO herdmates. Also, the 3-breed crossbreds had significantly higher survival to third (+11%) and fourth (+19%) calving compared with their HO herdmates. Across each generation of crossbreeding, the crossbreds had uniformly shorter stature, less angularity, and less body depth compared with their respective HO herdmates. The crossbred cows also had significantly less udder clearance from the hock but significantly more rear teat width and longer teat length compared with their respective HO herdmates. Furthermore, the crossbred cows had higher body condition score compared with their HO herdmates during each of their first 3 lactations.

Fertility and 305-day production of Viking Red-, Montbéliarde-, and Holstein-sired crossbred cows compared with Holstein cows during their first 3 lactations in Minnesota dairy herds.

Three generations of crossbred cows from a 3-breed rotation of the Viking Red (VR), Montbéliarde (MO), and Holstein (HO) breeds were compared with HO herdmates in 7 high-performance, commercial dairy herds in Minnesota. The designed study was initiated in 2008 with the enrollment of 3,550 HO females. Sires of cows were proven artificial insemination bulls and were high-ranking for genetic merit within each of the VR, MO, and HO breeds. The first generation of cows calved a first time from 2010 to 2017 and consisted of 644 VR × HO and 616 MO × HO 2-breed crossbreds and their 1,405 HO herdmates. The second generation calved a first time from 2012 to 2017 and consisted of 615 VR × MO/HO and 568 MO × VR/HO crossbreds and their 1,462 HO herdmates. The third generation calved a first time from 2014 to 2017 and was composed of 466 HO × VR/MO/HO and HO × MO/VR/HO crossbreds combined and their 736 HO herdmates. Collection of data ceased on December 31, 2017, and for the duration of study, many of the 2-breed and 3-breed crossbreds and their HO herdmates had the opportunity to complete at least 3 lactations, whereas the HO-sired crossbreds and their HO herdmates had the opportunity to complete 1 lactation. The 305-d actual (not mature equivalent) production of milk, fat, and protein was estimated from test-day observations with best prediction and cows with <305 DIM were projected to 305 d. The 2-breed and 3-breed crossbred cows had superiority over their HO herdmates for all of the fertility traits measured. The 2-breed crossbreds had -9, -17, and -15 d fewer days open than their HO herdmates during first, second, and third lactation, respectively. Also, the 3-breed crossbreds had -15, -19, and -20 d fewer days open than their HO herdmates during first, second, and third lactation, respectively. Cows in these herds had young ages at first calving of 22 to 23 mo across the breed groups, and the 3-breed crossbreds had significantly younger ages at first, second, and third calving than their HO herdmates. The 2-breed crossbreds had +2% higher fat plus protein production (kg) during first lactation, but did not differ during second and third lactation, from their HO herdmates. The 3-breed crossbreds had -3% to -4% lower fat plus protein production (kg) than their HO herdmates in each of their first 3 lactations. During first lactation, the HO-sired crossbreds did not differ for fat plus protein production (kg) from their HO herdmates.

Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated - an open-label pilot study.

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules. Methods: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months. Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported. Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.

Three-breed rotational crossbreds of Montbéliarde, Viking Red, and Holstein compared with Holstein cows for feed efficiency, income over feed cost, and residual feed intake.

Rotational 3-breed crossbred cows of Montbéliarde, Viking Red, and Holstein (CB) were compared with Holstein (HO) cows for alternative measures of feed efficiency as well as income over feed cost (IOFC) and residual feed intake (RFI) during the first 150 d of first, second, and third lactations. Primiparous and multiparous CB (n = 63 and n = 43, respectively) and HO (n = 60 and n = 37, respectively) cows were fed the same total mixed ration twice daily with refusals weighed once daily. Feed was analyzed for dry matter content, net energy for lactation, and crude protein content. Body weight (BW) was recorded twice weekly. Daily production of milk, fat, and protein were estimated from monthly test days with best prediction. Measures of efficiency from 4 to 150 d in milk (DIM) were feed conversion efficiency (FCE), defined as fat plus protein production (kg) per kilogram of dry matter intake (DMI); ECM/DMI, defined as kilograms of energy-corrected milk (ECM) per kilogram of DMI; net energy for lactation efficiency (NELE), defined as ECM (kg) per megacalorie of net energy for lactation intake; crude protein efficiency (CPE), defined as true protein production (kg) per kilogram of crude protein intake; and DMI/BW, defined as DMI (kg) per kilogram of BW. The IOFC was defined as revenue from fat plus protein production minus feed cost. The RFI from 4 to 150 DIM for each lactation was the residual error remaining from regression of DMI on milk energy output (Mcal), metabolic BW, and energy required for change in BW (Mcal). Statistical analysis of measures of feed efficiency and RFI for primiparous cows included the fixed effects of year of calving and breed group. For multiparous cows, statistical analysis included breed as a fixed effect and cow as a repeated effect nested within breed group. Primiparous CB cows had higher means for FCE (+5.5%), ECM/DMI (+4.0%), NELE (+4.0%), and CPE (+5.2%) and a lower mean DMI/BW (-5.3%) than primiparous HO cows. Primiparous CB cows ($875) also had higher mean IOFC than primiparous HO cows ($825). In addition, mean RFI from 4 to 150 DIM was significantly lower (more desirable) for primiparous CB cows than HO cows. Likewise, multiparous CB cows had higher means for FCE (+8.2%), ECM/DMI (+5.9%), NELE (+5.8%), and CPE (+8.1%) and a lower mean for DMI/BW (-4.8%) than multiparous HO cows. Multiparous CB cows ($1,296) also had a higher mean for IOFC than multiparous HO cows ($1,208) and a lower mean for RFI from 4 to 150 DIM than HO cows.

Three-breed rotational crossbreds of Montbéliarde, Viking Red, and Holstein compared with Holstein cows for dry matter intake, body traits, and production.

Rotational crossbred cows of the Montbéliarde, Viking Red, and Holstein (HO) breeds (CB) were compared with HO cows for dry matter intake (DMI), body weight (BW), cow height, body condition score (BCS), and production during the first 150 d of first, second, and third lactations. Primiparous and multiparous CB (n = 63 and 43, respectively) and HO (n = 60 and 37, respectively) cows calved from September 2014 to June 2017. Cows were fed the same total mixed ration twice daily, with refusals weighed once daily. The BW was recorded twice weekly, and height at the withers and the hips was recorded monthly. The BCS was evaluated weekly. The fat plus protein production from 4 to 150 d in milk was calculated from monthly test days using best prediction. Primiparous and multiparous cows were analyzed separately. Statistical analysis for primiparous cows included the fixed effects of year of calving and breed group, and the analysis for multiparous cows included the fixed effect of breed group and the repeated effect of cow nested within breed group. Primiparous CB cows (2,807 kg) had lower mean DMI than HO cows (2,948 kg) from 4 to 150 d in milk of first lactation. Mean BW was not different for the CB (562 kg) and HO (556 kg) cows, but primiparous CB cows had mean wither height that was 4.0 cm shorter and mean hip height that was 2.0 cm shorter than that of HO cows. Primiparous CB cows (3.46) had higher mean BCS compared with HO cows (3.20). Mean fat plus protein production did not differ for the primiparous CB and HO cows (331 vs. 329 kg, respectively). Multiparous CB cows (3,360 kg) also had lower mean DMI than HO cows (3,592 kg) and did not differ (636 kg) from HO cows (644 kg) for mean BW. The CB cows had mean wither height that was 3.5 cm shorter than that of HO cows, but mean hip height did not differ for multiparous CB (145.2 cm) and HO (146.4 cm) cows. Mean BCS was higher for multiparous CB cows (3.25) than for HO cows (3.06), and mean fat plus protein production was not different for multiparous CB (445 kg) and HO (441 kg) cows. The lower DMI of the CB cows than HO cows resulted in less feed cost without loss of revenue from fat plus protein production.

Social inequality and fractures-secular trends in the Danish population: a case-control study.

We examined links between markers of social inequality and fracture risk in the Danish population, demonstrating that high income and being married are associated with a significantly lower risk. INTRODUCTION: We explored whether the risk of hip, humerus, and wrist fracture was associated with markers of inequality using data from Danish health registries. METHODS: All patients 50 years or older with a primary hip (ICD10 S720, S721, S722, and S729) humerus (ICD10 S422, S423, S424, S425, S426, and S427), or wrist (ICD10: S52) fracture were identified from 1/1/1995 to 31/12/2011. Fracture patients were matched 1:1 by age, sex, and year of fracture, to a non-fracture control. Markers of inequality were as follows: income (fifths); marital status (married, divorced, widowed, or unmarried); area of residence (remote, rural, intermediate, or urban). Conditional logistic regression was used to investigate associations between these exposures, and risk of fracture, adjusting for covariates (smoking, alcohol, and Charlson co-morbidity). Interactions were fitted between exposure and covariates where appropriate. RESULTS: A total of 189,838 fracture patients (37,500 hip, 45,602 humerus, and 106,736 wrist) and 189,838 controls were included. Mean age was 73.9 years (hip), 67.5 years (humerus), and 65.3 years (wrist). High income (5th quintile) was significantly associated with a lower odds ratio of all three fractures, compared to average income (3rd quintile). Married subjects had a significantly decreased odds ratio across all three fractures. However, no overall secular difference was observed regarding the influence of the markers of inequality. CONCLUSION: In conclusion, we have demonstrated important, stable associations between social inequality, assessed using income, marital status, and area of residence, and fracture at the population level. These findings can inform approaches to healthcare, and suggest that much thought should be given to novel interventions aimed especially at those living alone, and ideally societal measures to reduce social inequality.

Causes of iron overload in blood donors - a clinical study.

BACKGROUND AND OBJECTIVES: Despite the obligate iron loss from blood donation, some donors present with hyperferritinaemia that can result from a wide range of acute and chronic conditions including hereditary haemochromatosis (HH). The objective of our study was to investigate the causes of hyperferritinaemia in the blood donor population and explore the value of extensive HH mutational analyses. MATERIALS AND METHODS: Forty-nine consecutive donors (f = 6, m = 43) were included prospectively from the Capital Regional Blood Center. Inclusion criteria were a single ferritin value >1000 µg/l or repeated hyperferritinaemia with at least one value >500 µg/l. All donors were questioned about their medical history and underwent a physical examination, biochemical investigations and next-generation sequencing of HH-related genes, including the HFE gene, the haemojuvelin gene (HFE2/HJV), the hepcidin gene (HAMP), the ferroportin 1 gene (SLC40A1) and the transferrin receptor 2 gene (TFR2). RESULTS: Forty of 49 donors were mutation positive with a combined 69 mutations, 54 of which were located in the HFE gene. There were 11 mutations in the TFR2 gene, two mutations in the HFE2 gene and two mutations in the HAMP gene. Only four donors had apparent alternative causes of hyperferritinaemia. CONCLUSION: HH-related mutations were the most frequent cause of hyperferritinaemia in a Danish blood donor population, and it appears that several different HH-genotypes can contribute to hyperferritinaemia. HH screening in blood donors with high ferritin levels could be warranted. HH-related iron overload should not in itself result in donor ineligibility.

Mesorhizobium sanjuanii sp. nov., isolated from nodules of Lotus tenuis in the saline-alkaline lowlands of Flooding Pampa, Argentina.

Two rhizobial strains, BSA136T and BSA150, related to the genus Mesorhizobium were isolated from root nodules of Lotus tenuis grown in saline-alkaline lowlands soil from Argentina. These strains showed different repetitive element palindromic PCR fingerprinting patterns but shared more than 99 % sequence similarity for both 16S rRNA and recA genes. Despite the symbiotic nodC gene sequences of our strains being related to the canonical Lotus biovar species comprising Mesorhizobium loti and Mesorhizobium japonicum, the 16S rRNA phylogenetic marker suggests that their taxonomical identities are closely related to Mesorhizobium helmanticense, Mesorhizobium metallidurans, Mesorhizobium thianshanense, Mesorhizobium gobiense and Mesorhizobium tarimense. Multilocus sequence analysis performed with seven housekeeping genes confirmed that BSA136T belongs to a separate clade within the genus Mesorhizobium. The results of comparisons for in silico DNA-DNA hybridization and average nucleotide identity indexes between the genomes of BSA136T and closest-related Mesorhizobium species were below the threshold for species delineation. Phenotypic features differentiated BSA136T from its closest-related species. On the basis of our results, BSA136T and BSA150 can be considered to represent a novel species of the genus Mesorhizobium, for which the name Mesorhizobium sanjuanii sp. nov. is hereby proposed. The type strain of this species is BSA136T (=CECT 9305T=LMG 30060T), for which the draft genome sequence is available.