Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

Milk component ratios and their associations with energy balance indicators and serum calcium concentration in early-lactation spring-calving pasture-based dairy cows.

Indirect assessment of metabolic status using milk samples provides a non-invasive and objective tool for cow-level health monitoring. Milk fat-to-protein ratio (FPR) has been commonly evaluated as an indirect measure for negative energy balance (EB) in confined dairy cows. However, milk component ratios have not been explored for their association with pasture-based cows' metabolic status. The objectives of this observational study were to 1) describe milk component ratios from 0 to 45 d postpartum, 2) evaluate the associations between milk component ratios [FPR, fat-to-lactose (FLR), protein-to-lactose (PLR)] and indicators of EB (serum ß-hydroxybutyrate (BHB) concentration at 5-45 d postpartum and body condition score (BCS) change during the transition period), and 3) evaluate the associations between milk component ratios and serum Ca concentration 0-4 d postpartum in spring-calving dairy cows from pasture-based commercial farms. Milk component ratios were determined on samples collected before AM or PM milkings from 548 cows at 0-45 d postpartum (n = 970). Serum BHB and Ca determinations were performed in blood samples collected at the time of milk sample collection at 5-45 d postpartum (n = 918) and 0-4 d postpartum (n = 50), respectively; and BCS change was calculated using BCS assigned between 29 d prepartum and 45 d postpartum (n = 851). Cows' calving date, parity (1st, 2nd-3rd or ≥ 4th) and breed (Holstein-Friesian or dairy crossbred) information was obtained from the farm records. Data was analyzed by multiple linear regression. Average milk FPR, FLR and PLR were 0.70, 0.53 and 0.72, respectively. Milk FPR linearly increased while milk FLR linearly decreased postpartum both at a rate of 0.004 units per day; milk PLR decreased 0.05 units per day for the first 30 d postpartum and moderately increased afterward. Milk FPR and FLR were 0.71 and 0.52 units lower before AM than PM milking, respectively; while milk PLR was similar before AM and PM milking. Milk FPR and FLR were 0.07 to 0.10 units higher for 2nd-3rd compared with 1st and ≥ 4th parity cows. Milk PLR was 0.03 units greater for ≥ 4th compared with 2nd-3rd and 1st parity cows. Further, crossbred cows had 0.07, 0.08 and 0.03 higher milk FPR, FLR and PLR than Holstein-Friesian cows, respectively. Moderate to high P-values along with moderate to small estimated slopes and wide 95% confidence intervals were observed for the associations between milk component ratios and indicators of EB. A positive linear association was observed between milk FPR and serum Ca concentration within 4 d postpartum; milk FPR increased 0.31 units per each mmol/L increase in serum Ca concentration. Cows with low serum Ca concentration within 4 d postpartum had 0.27 units lower milk FPR compared with cows at or above the threshold (2.12 mmol/L), and tended to have 0.15 units lower milk FPR compared with cows at or above the threshold (2.00 mmol/L). In conclusion, further research is needed to reach conclusions on the association between milk component ratios determined before milking and EB indicators. The potential of milk FPR for monitoring blood Ca status warrants further investigation in early-lactation pasture-based dairy cows.

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

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

[The history of lithium]. / De geschiedenis van lithium.

Background Lithium is the first choice for maintenance treatment of bipolar disorder. How was discovered that lithium is such an effective treatment for mood episodes? Aim To gain understanding in how lithium obtained its value in the pharmacotherapeutic treatment of bipolar disorder. Method Literature research into the use of lithium in the history of psychiatry. Results In 1949 John Cade discovered the usability of lithium in the treatment of mania. Subsequently, it was discovered that lithium prevents mood episodes in bipolar disorder, can be used in the treatment of unipolar depression as an addition to an antidepressant, and lowers the risk of suicidality. Conclusion Since the nineteenth century lithium is used in psychiatry. Mid twentieth century the therapeutic value of lithium was discovered in the treatment of bipolar disorder and many international guidelines consider lithium as ‘a golden standard’. However, with the arrival of other psychopharmaca lithium is prescribed less in the last decades. It is important to teach psychiatrists and nurse specialists how to use lithium because of its important value in the treatment of bipolar disorder.

Should germline genome editing be allowed? The effect of treatment characteristics on public acceptability.

STUDY QUESTION: To what extent do characteristics of germline genome editing (GGE) determine whether the general public supports permitting the clinical use of GGE? SUMMARY ANSWER: The risk that GGE would cause congenital abnormalities had the largest effect on support for allowing GGE, followed by effectiveness of GGE, while costs, the type of application (disease or enhancement) and the effect on child well-being had moderate effects. WHAT IS KNOWN ALREADY: Scientific progress on GGE has increased the urgency of resolving whether and when clinical application of GGE may be ethically acceptable. Various expert bodies have suggested that the treatment characteristics will be key in determining whether GGE is acceptable. For example, GGE with substantial risks (e.g. 15% chance of a major congenital abnormality) may be acceptable to prevent a severe disease but not to enhance non-medical characteristics or traits of an otherwise healthy embryo (e.g. eye colour or perhaps in the future more complex traits, such as intelligence). While experts have called for public engagement, it is unclear whether and how much the public acceptability of GGE is affected by the treatment characteristics proposed by experts. STUDY DESIGN, SIZE, DURATION: The vignette-based survey was disseminated in 2018 among 1857 members of the Dutch general public. An online research panel was used to recruit a sample representing the adult Dutch general public. PARTICIPANTS/MATERIALS, SETTING, METHODS: A literature review identified the key treatment characteristics of GGE: the effect on the well-being of the future child, use for disease or enhancement, risks for the future child, effectiveness (here defined as the chance of a live birth, assuming that if the GGE was not successful, the embryo would not be transferred), cost and availability of alternative treatments/procedures to prevent the genetic disease or provide enhancement (i.e. preimplantation genetic testing (PGT)), respectively. For each treatment characteristic, 2-3 levels were defined to realistically represent GGE and its current alternatives, donor gametes and ICSI with PGT. Twelve vignettes were created by fractional factorial design. A multinominal logit model assessed how much each treatment characteristic affected participants' choices. MAIN RESULTS AND THE ROLE OF CHANCE: The 1136 respondents (response rate 61%) were representative of the Dutch adult population in several demographics. Respondents were between 18 and 89 years of age. When no alternative treatment/procedure is available, the risk that GGE would cause (other) congenital abnormalities had the largest effect on whether the Dutch public supported allowing GGE (coefficient = -3.07), followed by effectiveness (coefficient = 2.03). Costs (covered by national insurance, coefficient = -1.14), the type of application (disease or enhancement; coefficient = -1.07), and the effect on child well-being (coefficient = 0.97) had similar effects on whether GGE should be allowed. If an alternative treatment/procedure (e.g. PGT) was available, participants were not categorically opposed to GGE, however, they were strongly opposed to using GGE for enhancement (coefficient = -3.37). The general acceptability of GGE was higher than participants' willingness to personally use it (P < 0.001). When participants considered whether they would personally use GGE, the type of application (disease or enhancement) was more important, whereas effectiveness and costs (covered by national insurance) were less important than when they considered whether GGE should be allowed. Participants who were male, younger and had lower incomes were more likely to allow GGE when no alternative treatment/procedure is available. LIMITATIONS, REASONS FOR CAUTION: Some (e.g. ethnic, religious) minorities were not well represented. To limit complexity, not all characteristics of GGE could be included (e.g. out-of-pocket costs), therefore, the views gathered from the vignettes reflect only the choices presented to the respondents. The non-included characteristics could be connected to and alter the importance of the studied characteristics. This would affect how closely the reported coefficients reflect 'real-life' importance. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to quantify the substantial impact of GGE's effectiveness, costs (covered by national insurance), and effect on child well-being on whether the public considered GGE acceptable. In general, the participants were strikingly risk-averse, in that they weighed the risks of GGE more heavily than its benefits. Furthermore, although only a single study in one country, the results suggests that-if sufficiently safe and effective-the public may approve of using GGE (presumably combined with PGT) instead of solely PGT to prevent passing on a disease. The reported public views can serve as input for future consideration of the ethics and governance of GGE. STUDY FUNDING/COMPETING INTEREST(S): Young Academy of the Royal Dutch Academy of Sciences (UPS/RB/745), Alliance Grant of the Amsterdam Reproduction and Development Research Institute (2017-170116) and National Institutes of Health Intramural Research Programme. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

[Reverse abdominoplasty in the presence of bi-subcostal scar: Technical note]. / Abdominoplastie inversée en présence d'une cicatrice bi-sous-costale : note technique.

INTRODUCTION: The presence of horizontal supraumbilical scars increases the risk of vascular complications after a large abdominoplasty. We present here a technique of abdominal dermolipectomy with umbilical transposition called « reverse ¼, in the presence of a bi-subcostal scar. TECHNICAL NOTE: The reverse abdominoplasty technique consists in uninserting the umbilicus, detaching the supra-umbilical and sub-umbilical soft tissues by assessing the existing bi-subcostal scar in order to pull the skin upwards, and to remove the supra-umbilical excess skin, before bringing the umbilicus back to its proper position. DISCUSSION: This technique is a good alternative to perform an abdominal dermolipectomy in a patient with a history of bi-subcostal scarring without increasing the risk of abdominal skin necrosis, and without complicating or lengthening the conventional surgical procedure, provided that the upper redraping is achievable with sufficient upper excess skin and laxity.

Considerations for the design of nutrition-sensitive production programmes in rural South Africa.

BACKGROUND: Very little has been researched about the efficacy, effectiveness, feasibility, sustainability and impact of food-based approaches on the diets and nutritional status of populations at risk of hunger and food insecurity. This study contributes knowledge about the impact of food-based approaches on the diets of populations at risk of hunger and food insecurity in four of the poorest rural communities in South Africa. The study investigated the consumption and production patterns of rural households (278 in summer and 280 in winter) in four sites in the poorest municipalities in South Africa. METHODS: A multistage stratified random sampling technique was applied to identify the communities and sample households for the quantitative survey and qualitative assessments. Qualitative and quantitative data were collected between 2013 and 2015 through focus group discussions (FGDs), key informant interviews and the two-round panel survey to cover both the summer and winter seasons at each site. RESULTS: Home gardening led to a significant positive increase in the consumption of white roots and tubers, dark green leafy vegetables, orange-coloured fruit and other fruit in the 24 h prior to the survey. Participation in a community garden led to significant increases in the consumption of dark green leafy vegetables and other vegetables. School gardening did not demonstrate any statistical relationships with the consumption of foods from the crop-related food groups. Crop production improved dietary diversity. Selling produce and irrigation showed a stronger improvement in dietary diversity. Seasonality affected the availability of fresh fruit and vegetables for home consumption in winter. CONCLUSIONS: Producing beyond that solely for home consumption has greater benefits for dietary diversity and a consumption-smoothing effect during the post-harvest period. Politicians and the scientific community should recognise the role that household and small-scale crop production plays in supporting household consumption and the provision of essential micronutrients despite constraints and disincentives. Production and education programmes should focus on strengthening existing good consumption patterns and promoting the consumption of foods that can improve dietary diversity.

Graduate Student Literature Review: Evaluating the appropriate use of wearable accelerometers in research to monitor lying behaviors of dairy cows.

Until recently, animal behavior has been studied through close and extensive observation of individual animals and has relied on subjective assessments. Wearable technologies that allow the automation of dairy cow behavior recording currently dominate the precision dairy technology market. Wearable accelerometers provide new opportunities in animal ethology using quantitative measures of dairy cow behavior. Recent research developments indicate that quantitative measures of behavior may provide new objective on-farm measures to assist producers in predicting, diagnosing, and managing disease or injury on farms and allowing producers to monitor cow comfort and estrus behavior. These recent research developments and a large increase in the availability of wearable accelerometers have led to growing interest of both researchers and producers in this technology. This review aimed to summarize the studies that have validated lying behavior derived from accelerometers and to describe the factors that should be considered when using leg-attached accelerometers and neck-worn collars to describe lying behavior (e.g., lying time and lying bouts) in dairy cows for research purposes. Specifically, we describe accelerometer technology, including the instrument properties and methods for recording motion; the raw data output from accelerometers; and methods developed for the transformation of raw data into meaningful and interpretable information. We highlight differences in validation study outcomes for researchers to consider when developing their own experimental methodology for the use of accelerometers to record lying behaviors in dairy cows. Finally, we discuss several factors that may influence the data recorded by accelerometers and highlight gaps in the literature. We conclude that researchers using accelerometers to record lying behaviors in dairy cattle should (1) select an accelerometer device that, based on device attachment and sampling rate, is appropriate to record the behavior of interest; (2) account for cow-, farm-, and management-related factors that could affect the lying behaviors recorded; (3) determine the appropriate editing criteria for the accurate interpretation of their data; (4) support their chosen method of recording, editing, and interpreting the data by referencing an appropriately designed and accurate validation study published in the literature; and (5) report, in detail, their methodology to ensure others can decipher how the data were captured and understand potential limitations of their methodology. We recommend that standardized protocols be developed for collecting, analyzing, and reporting lying behavior data recorded using wearable accelerometers for dairy cattle.

Associations between lying behavior and activity and hypocalcemia in grazing dairy cows during the transition period.

Hypocalcemia is a common metabolic disorder of transition dairy cows that is considered a gateway disease, increasing the risk of other health disorders and reducing cow performance. Clinical milk fever is associated with long periods of recumbency, and it is plausible that cows experiencing non-paretic hypocalcemia may spend more time lying; hence, lying behavior and activity measures may be useful in identifying at-risk cows. The objective of this study was to describe associations among blood calcium (Ca) status at calving and lying behavior and activity measures during the transition period in grazing dairy cows. Blood was sampled on the day of calving (d 0), and d 1, 2, 3, and 4 postcalving, and analyzed for total plasma Ca concentration. Twenty-four multiparous Holstein-Friesian and Holstein-Friesian × Jersey grazing dairy cows were classified, retrospectively, as clinically hypocalcemic (CLIN; blood Ca ≤ 1.4 mmol/L at 1 or more consecutive samplings within 48 h postcalving, but without parturient paresis). These cows were pair-matched (using milk production potential from their estimated breeding value for milk protein, mean body weight at wk -5 and -6 precalving, and, where possible, parity) with 24 cows classified as subclinically hypocalcemic (SUB; blood Ca > 1.4 and < 2.0 mmol/L at 2 consecutive samplings within 48 h postcalving), and 24 cows classified as normocalcemic (NORM; blood Ca ≥ 2.0 mmol/L at 3 consecutive samplings within 72 h postcalving). Lying behavior and activity were monitored using triaxial accelerometers from -21 to +35 d relative to calving. Data were summarized to calculate daily lying time (h/d), daily number of lying bouts (LB; no./d), mean LB duration (min/bout), and the number of steps taken (steps/d). On d 0, the CLIN group were less active and spent approximately 2.6 h longer lying than the SUB and NORM groups, particularly between 0200 and 1400 h. On d 0, the NORM group had fewer LB (16.3/d) than the SUB and CLIN groups (18.2 and 19.2/d, respectively). These differences in behavior were no longer detected 2 d postcalving, and no further differences were observed. The day before calving, the CLIN group spent 1.4 h longer lying down than did the SUB and NORM groups. Further, the relative change in steps from a precalving baseline period (d -14 to -7) until d 0 was positively, linearly associated with blood Ca concentration within 24 h postcalving. Future work should consider daily and temporal changes in behavior in individual cows to determine the potential for these measures to allow early detection of hypocalcemia.

Lack of diagnostic utility of the ECG-derived ventricular gradient in patients with suspected acute pulmonary embolism.

INTRODUCTION: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm. METHODS: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated. RESULTS: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases. CONCLUSIONS: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. CONDENSED ABSTRACT: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied.

Selenium requirements in grazing dairy cows: a review.

In New Zealand, the recommended intake of Se for dairy cattle (0.03 mg/kg dry matter (DM)) is lower than in the United Kingdom and Australia (0.1 and 0.04 mg/kg DM, respectively), and much lower than in the United States of America (0.3 mg/kg DM). Advisors in New Zealand often suggest that New Zealand intake recommendations are far too low and that recommendations from the United States of America should be used. This has created confusion as farmers are given very different advice depending on which recommendations their advisor uses. In this review, we assess whether the published evidence supports the existing dietary requirements and associated Se status thresholds, or if change is required. We focus particularly on the evidence-base in cattle fed a primarily pasture-based diet, as it is critical that dietary recommendations are derived from data created using cows fed similar diets. Accordingly, we also consider whether the increased use of fodder crops, especially during the dry period, is likely to have altered the Se requirements of dairy cows in New Zealand. We report that the science behind the dietary requirements for Se is robust, being supported by factorial models validated using New Zealand data, and on-farm experimental studies. Published nutritional data suggest that the increased use of fodder crops is unlikely to have altered the dietary balance of pro- and antioxidant factors in New Zealand dairy cows in a way that would meaningfully affect Se requirements. However, the lack of specific data on the vitamin E and fatty acid content of the crops being fed in New Zealand means that more information is needed to confirm this conclusion. In general, the existing New Zealand recommendations for Se-status thresholds are supported, although studies are still lacking to properly characterise the upper threshold of the marginal range. Nevertheless many studies in New Zealand, of herds with marginal or low adequate Se status (using New Zealand recommendations), have failed to show an effect of Se supplementation on milk production, intramammary infection or reproductive performance, so it is highly unlikely that the upper threshold of the range is much higher than the current recommendation. Proponents of the hypothesis that Se intakes in New Zealand dairy cattle should be increased by at least 10 times the current recommendations are therefore not using the evidence base correctly.

The palatal mucosal graft: The adequate posterior lamellar reconstruction in extensive full-thickness eyelid reconstruction.

INTRODUCTION: Full-thickness eyelid defects exceeding 25% of the eyelid width should benefit from a skillful, immediate and simultaneous reconstruction of two layers; anterior and posterior lamella. In this article, we recall, through an original series of cases, the possibility of using a palatal fibromucosal graft during the reconstruction of the posterior lamella as well as the modalities of its optimal use. PATIENTS AND METHODS: Retrospective study, including 8 patients with an extensive full-thickness eyelid defect affecting more than half of the upper and/or lower eyelid, after tumor excisions. 4 cases were involved in lower eyelid reconstruction, 2 in upper one and 2 in both. Posterior lamella was reconstructed using a palatal mucosal graft. Anterior lamella was reconstructed using different flaps: Esser-Mustardé flap, medially and laterally based orbicularis oculi myocutaneous flap, Tripier and orbitonasolabial flaps. Mean follow-up was 12.75 months. RESULTS: The survival rate of grafts and flaps was excellent with only one flap border necrosis. The donor site healed in an average time of 3 weeks. Functional recovery, complete eye closure and opening, was obtained in all cases. Lining, texture and color was considered satisfactory in all cases. CONCLUSION: The palatal mucosal graft provides a good and lasting structural support to the eyelid, which is essential for the inferior eyelid, especially when combined with a flap. Slight overcorrection is recommended.

Lying behavior and activity during the transition period of clinically healthy grazing dairy cows.

Lying behavior and activity may provide useful information for the prediction of an imminent calving and the health of transition dairy cows; however, it is important first to understand what constitutes typical lying behavior and activity because this has not been defined for grazing dairy cows during the transition period. Our objective was to describe changes in lying behavior and activity in grazing dairy cows during the transition period using varying phenotypes typical of commercial dairy herds under grazing systems. Behavior data from IceTag or IceQube (IceRobotics, Edinburgh, Scotland) triaxial accelerometers were collected for 310 cow parities from multiparous, mixed-age (mean ± standard deviation; 4.5 ± 1.65 yr), and mixed-breed [Holstein-Friesian (HF), n = 216; and HF × Jersey, n = 94] grazing dairy cows from 4 parent experiments. The IceTags or IceQubes captured lying and activity data during the transition period (-21 to 34 d relative to calving) to allow the calculation of daily lying time (h/d), daily lying bouts (LB; no./d), mean LB duration (min/bout), and the number of steps taken (steps/d). Lying behavior and activity were analyzed using a repeated measures ANOVA during 3 periods: PRE (-21 to -3 d), POST (3 to 21 d), and the day of calving (d 0). Lying time was lower on d 0 (7.25 h/d) compared with PRE and POST lying times (10.3 and 8.58 h/d, respectively), with more frequent LB on d 0 (12.9 no./d) compared with the PRE and POST daily LB (8.15 vs. 7.74 no./d). Cows took more steps POST (4,424 steps/d) compared with d 0 and PRE (4,105 and 2,289 steps/d, respectively). Regression analysis determined that daily lying time decreased substantially from -3 to 0 d (slope = -1.03 ± 0.07 h/d) and from -2 and -1 d for daily LB (slope = 5.09 ± 0.54 no./d), which may be due to the calving event itself but also reflect restlessness. Daily lying time, daily LB, LB duration, and number of steps taken were substantially altered at the time of the calving event in grazing dairy cows. Cows were more active, spent less time lying, and took more steps postcalving compared with precalving, and it appears that this behavior may largely be due to activity associated with twice daily milking. Mean lying behavior and activity measures were more highly variable across individuals than across groups. Information available via activity monitors may contribute to the improvement of individual management of transition dairy cows, and this research provides a benchmark for typical changes in behavior during the transition period in grazing systems.

Broad support for regulating the clinical implementation of future reproductive techniques.

STUDY QUESTION: Do gynaecologists, infertile patients and the general public, consider that regulation of the clinical implementation of stem cell-based fertility treatments is required? SUMMARY ANSWER: There is broad support from gynaecologists, patients and the general public for regulating the clinical implementation of future stem cell-based fertility treatments. WHAT IS KNOWN ALREADY: There is debate on the need to regulate the clinical implementation of novel techniques. Regulation may hinder their swift adoption and delay benefits for patients, but may prevent the implementation of ineffective or harmful techniques. Stem cell-based fertility treatments, which involve creating oocytes or spermatozoa by manipulating stem cells, are likely to be implemented in clinical practice in the near future and will probably impact future generations as well as the current one. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey was conducted among gynaecologists working in fertility clinics (n = 179), patients with severe infertility (n = 348) and a representative sample of the general public (n = 1250). The questionnaire was disseminated in the Netherlands in the winter of 2015-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The newly developed questionnaire was reviewed by experts and tested among the general public. The questionnaire assessed whether participants wanted each of nine potential negative consequences of the clinical implementation of stem cell-based fertility treatments to be regulated. In addition, the importance of all negative and positive potential consequences, the appropriate regulatory body and its need to consult with advisors from various backgrounds was questioned. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 958 respondents completed the questionnaire (response rate: 54%). A large majority of each participant group (>85%) wanted regulation, for at least one potential negative consequence of the clinical implementation of stem cell-based fertility treatments. The majority of all participant groups wanted regulation for serious health risks for intended parents, serious health risks for children and the disposal of human embryos. Regulation for out-of-pocket costs and the burden of treatment received little support. The majority of gynaecologists and the general public, but not the patients, requested regulation for the risk of minor congenital abnormalities, the success rates and the naturalness of treatments. Nevertheless, the majority of patients did consider the former two potential negative consequences important. The majority of all groups preferred a national bioethics committee as the regulatory body. This committee should consult with advisors from various backgrounds and should consider the broader context of potential consequences of the stem cell-based fertility treatments. LIMITATIONS, REASONS FOR CAUTION: This empirical study focuses on only three stakeholder groups. This study reports on the perspective of the majority and this is not per definition the morally right perspective. The transferability of our findings to other cultures and other techniques remains unclear. WIDER IMPLICATIONS OF THE FINDINGS: A national bioethics committee, consulting with advisors from various backgrounds, should regulate the clinical implementation of future stem cell-based fertility treatments. Whether this broad support for regulation applies to novel techniques from other fields of medicine should be examined. STUDY FUNDING/COMPETING INTEREST(S): The Young Academy of the Royal Netherlands Academy of Arts and Sciences. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

[Breast reconstruction by latissimus dorsi myocutaneous flap and implant: The dorsal bra technique]. / Reconstruction mammaire par lambeau musculo-cutané de grand dorsal avec prothèse : la technique du soutien-gorge dorsal.

Despite the development of microsurgical techniques, latissimus dorsi myocutaneous pedicle flap remains mainly used in breast reconstruction surgery. It is reliable and could be performed on almost all the patients, even if they smoke. It is also a good indication in case of irradiation. The technical alternative, which combines latissimus dorsi myocutaneous flap and an implant, allows the reconstruction of the expected volume and enables controlateral implant augmentation if the patient desires. The dorsal skin paddle increases the cutaneous pocket. The muscle in-depth enhances the irradiated skin and protects the implant. Positioning the skin paddle on the breast area is essential: it should be based on the mastectomy scar or on an added contraincision barring it. Thus it allows the muscle to embrace the implant as a bra. The precise reference points helping the placement of the flap could be reproduced and ensure pleasant and stable results over time.

The acceptability of stem cell-based fertility treatments for different indications.

STUDY QUESTION: What is the acceptability of using stem cell-based fertility treatments (SCFT) for different indications according to gynaecologists and the general public? SUMMARY ANSWER: The majority of gynaecologists and the general public accept SCFT for the indications female or male infertility in young heterosexual couples, and female infertility in single women and same-sex couples. WHAT IS KNOWN ALREADY: SCFT could result in genetic parenthood for intended parents with indications that cannot be treated using currently available methods, such as being in a same-sex relationship or female post-menopausal age. It is unclear whether the acceptability of SCFT differs between indications for treatment and whether gynaecologists and the general public differ in their assessments. STUDY DESIGN SIZE, DURATION: In November 2015, a cross-sectional survey was disseminated among 179 gynaecologists and a panel of 1250 respondents comprising a representative sample of the Dutch general public. PARTICIPANTS/MATERIALS, SETTING, METHODS: The potential indications for future SCFT to achieve genetic parenthood were identified by literature review. A questionnaire was developed, reviewed by experts from different disciplines and tested among the general public. The questionnaire asked whether treating eight groups of intended parents with SCFT was acceptable or not. Regression analysis examined whether demographic characteristics influenced choices and whether the general public and gynaecologists differed in opinion. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 82 (46%) gynaecologists and 772 (62%) members of the general public completed the survey. The acceptability of using SCFT varied according to both gynaecologists and the general public between the eight groups of intended parents (P < 0.001). The majority of the Dutch general public accepts SCFT for six out of eight possible indications, namely female infertility in young heterosexual couples (94%), male infertility in young heterosexual couples (94%), unexplained infertility in young heterosexual couples (83%), female infertility in single women (69%), lesbian couples (68%) and gay couples (62%). The majority of gynaecologists also found treating these groups acceptable, except for the indication of unexplained infertility, which was only accepted by a minority of gynaecologists (43%). A minority of both the general public and gynaecologists accepted SCFT for fertile women who want a child that is genetically only her own (27 and 6%, respectively) and for female infertility in heterosexual couples in which the woman is over 50 years of age (17% and 26%, respectively). Attaching low importance to religion, having progressive political preferences, not having a university degree, having experienced infertility, being a woman, being older and not being of European ethnicity were positively associated with considering using SCFT acceptable for one or multiple indications. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The generalizability of our findings to future decades or other countries might be limited as opinions about novel technologies change over time and might vary across cultures. Support among gynaecologists and the general public is interesting but not proof of ethical acceptability. WIDER IMPLICATIONS OF THE FINDINGS: Once proven safe and effective, fear of limited acceptability by the general public is unwarranted, and thus should not stop gynaecologists from offering SCFT to single infertile women and same-sex couples in addition to young infertile heterosexual couples. STUDY FUNDING AND COMPETING INTEREST(S): Funded by the Young Academy of the Royal Netherlands Academy of Arts and Sciences and the Universities of Amsterdam and Leuven. No conflict of interest to declare.

The importance of genetic parenthood for infertile men and women.

STUDY QUESTION: Do men and women beginning to attend a fertility clinic prefer genetic over non-genetic parenthood? SUMMARY ANSWER: Nearly, all infertile men and women prefer genetic parenthood. WHAT IS KNOWN ALREADY: Clinicians assume that all infertile couples prefer genetic parenthood over non-genetic parenthood and, therefore, consider treatments with donor gametes an option of last resort. Previous studies of the desire for parenthood identified 30 motivations for genetic parenthood, and 51 motivations for which having a genetically related child is not strictly necessary but might be deemed required. The exact strength of the preference of infertile men and women for genetic parenthood remains unclear, as does the importance of the various motivations. STUDY DESIGN, SIZE, DURATION: A questionnaire was developed based on a literature review. It was assessed by professionals and pilot tested among patients. The coded paper-pencil questionnaire was disseminated among both partners of 201 heterosexual infertile couples after their first consultation at one of two Belgian fertility clinics between October 2015 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey addressed: (i) the preference for genetic parenthood for themselves and for their partner, (ii) the importance of 30 motivations for genetic parenthood and (iii) the importance of 51 other motivations for parenthood and whether these motivations require being the genetic parent of their child to be fulfilled. To simplify presentation of the results, all 81 motivations were grouped into reliable categories of motivations using psychometric analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The survey was completed by 104 women and 91 men (response rate: 49%). Almost all respondents (98%) favored genetic over non-genetic parenthood for both their partner and themselves. One-third of the respondents stated they only wanted to parent their own genetically related child. Achieving genetic parenthood for their partner was considered significantly more important than achieving genetic parenthood for themselves. Within couples, men had a stronger preference for genetic parenthood (P = 0.004), but this was not significant after correction for educational level, which was significantly associated with the preference of both men and women. The 30 motivations for becoming a genetic parent clustered into 11 categories of which 'to experience a natural process' was deemed most important. The 51 motivations for becoming a parent for which having a genetically related child is not strictly necessary clustered into 14 categories of which 'to contribute to a child's well-being' and 'to experience the love of a child' were most important. Respondents deemed they would need to be the genetic parent of their child to fulfill nearly all their motivations for parenthood. LIMITATIONS REASONS FOR CAUTION: We included couples that visited the fertility clinic for the first time, and the preference for genetic parenthood might change throughout a fertility treatment trajectory. Moreover, what prospective parents expect to be important for their future well-being might not really define parents' well-being. WIDER IMPLICATIONS OF THE FINDINGS: The presumed preference of couples for genetic parenthood was confirmed. Resistance against using donor gametes is more likely among lower educated individuals. Researching whether non-genetic parents actually feel they cannot fulfill the 51 motivations for parenthood, could be a basis for developing patient information. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Parkes Foundation, the University of Amsterdam and the Leuven University Hospital. No conflict of interest.

Couples with non-obstructive azoospermia are interested in future treatments with artificial gametes.

STUDY QUESTION: Would couples diagnosed with non-obstructive azoospermia (NOA) consider two future treatments with artificial gametes (AGs) as alternatives for testicular sperm extraction followed by ICSI (TESE-ICSI)? SUMMARY ANSWER: Most couples with NOA (89%) would opt for treatment with AGs before attempting TESE-ICSI and/or after failed TESE-ICSI. WHAT IS KNOWN ALREADY: Couples with NOA who undergo TESE-ICSI have a 25% chance of conceiving a child. Two future treatments that are being developed are 'ICSI with artificial sperm formed from somatic cells' (ICSI with AGs) and 'natural conception after autotransplantation of in vitro proliferated spermatogonial stem cells' (natural conception with AGs). It is unknown what treatment preferences patients have. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey conducted in 2012-2013, addressing all 921 couples diagnosed with NOA and treated with TESE-ICSI in Dutch fertility clinics between 2007 and 2012. The coded questionnaires were sent by mail and followed up with two reminders. PARTICIPANTS/MATERIALS, SETTING, METHODS: We developed the questionnaire based on a literature review and previous qualitative interviews, and included treatment preference and the valuation of nine treatment characteristics. We assessed reliability of the questionnaires and calculated mean importance scores (MISs: 0-10) of each treatment characteristic. We assessed which patient and treatment characteristics were associated with a couple's hypothetical treatment preference using binominal regression. MAIN RESULTS AND THE ROLE OF CHANCE: The vast majority (89%) of the 494 responding couples (response rate: 54%) would potentially opt for AGs as a first and/or a last resort treatment option. More specifically, as a first treatment couples were likely (67%) to prefer natural conception with AGs over TESE-ICSI and less likely to prefer ICSI with AGs over TESE-ICSI (34%). After failed TESE-ICSI, the majority of couples (75%) would want to attempt ICSI with AGs as a last resort option. The most important characteristics of treatment were safety for children (MIS: 8.2), pregnancy rates (MIS: 7.7) and curing infertility (MIS: 6.8). Costs, burden, naturalness and technological sophistication were of about equal importance (MIS: 3.1-4.0). The majority of patients rated conception at home and moral acceptability as not important (MIS: 1.7 and 0.8, respectively), but the importance attributed to these variables did still affect patients' likeliness to opt for AGs. LIMITATIONS AND REASONS FOR CAUTION: Couples with NOA not opting for TESE-ICSI were not included and might have other perspectives. Couples' hypothetical choices for AGs might differ from their actual choices once data on the costs, safety and pregnancy rates become available from these new treatment options. WIDER IMPLICATIONS OF THE FINDINGS: The interest of couples with NOA in potential future treatments with AGs encourages further pre-clinical research. Priority setting for research and future decision-making on clinical application of AGs should take all characteristics important to patients into account. STUDY FUNDING/COMPETING INTERESTS: The authors report no financial or other conflict of interest relevant to the subject of this article.

Enlargement of the flexor pulleys by an omega plasty: A study comparing the release of one or both sides of the A2 and/or A4 pulley.

PURPOSE: The omega plasty on one side of the A2 and/or A4 pulley improves the gliding of repaired flexor tendons in zone II. The purpose of this study was whether or not the enlargement of the digital channel was better after the release of one or both sides of each pulley. METHODS: In fresh cadavers, the technique was to first disinsert the ulnar attachments of the A2 and A4 pulleys and then the radial insertions. An ultrasound was used to measure the large axis, the circumference, and the cross-sectional surface of each of A2 and A4 pulleys before release, after ulnar release and after radial release. RESULTS: The release of the A2 pulley reduces the risk of conflict in the sutured flexor tendons in the digital channel. The release of the A4 pulley seems less effective than that of A2. The release of the two pulleys reduces the risk of conflict in one sutured zone of the flexor tendons in the digital channel. CONCLUSION: In all, if there is a conflict between the flexor tendons sutured opposite A2, we recommend an omega plasty on the two sides of the pulley. If the conflict appears opposite A4, we recommend the plasty of the two sides of A4 and A2.

The DIEP flap breast reconstruction: Starting from scratch in a university hospital.

PURPOSE: The deep inferior epigastric perforator (DIEP) flap provides excellent results when performed by a trained surgical team. However, the beginning of the procedure is often complicated. To date, few authors have published their initial experiences. This study presents our team's experience using a DIEP flap in breast reconstruction. METHODS: From June 2008 until December 2013, the same leading operator performed 132 consecutive DIEP flaps. Breast reconstructions were immediate (n=18) or delayed (n=114), unilateral (n=110) or bilateral (n=11). The learning curve was assessed using the operating time, ischemic time, postoperative hospital stay, and complications. For statistical comparisons, unilateral reconstructions were divided into five chronologic groups of 22 consecutive DIEP flaps and two chronologic groups of 55 flaps. RESULTS: The average time of surgery was 291 min (range, 185-645) for unilateral breast reconstruction and 513 min (range, 400-790) for bilateral breast reconstruction. The global complication rate was 24.5%. In the unilateral series, the time of surgery decreased progressively from 415 min to 233 min (P=4.8×10(-8)). The mean postoperative hospital stay was reduced from 7.14 days to 6.32 days (P=0.042). The complications and flap failure rates had regular time distributions. Initially, the revision rate reached 50% for the first ten unilateral cases but decreased rapidly and remained steady at 6% for the following cases (P=0.0012). CONCLUSIONS: Our initial experience of DIEP flap breast reconstruction showed a significant improvement of surgical performances exceeding 50 cases, with a critical ten first case period.