High Entropy Alloys (HEA), where five or more elements are mixed together in near equiatomic ratios offer promising properties as hydrogen storage materials due to their ability to crystallize in ...simple cubic structures in the presence of large lattice strain originating from the different sizes of the atoms. In this work, the hydrogen absorption and desorption as well as the cycling properties of the TiZrNbHfTa HEA have been studied by in situ Synchrotron X-Ray diffraction, Pressure-Composition-Isotherm, Thermal Desorption Spectroscopy and Differential Scanning Calorimetry. The alloy crystallizes in a cubic bcc phase and undergoes a two-stage hydrogen absorption reaction to a fcc dihydride phase with an intermediate tetragonal monohydride, very similar to the V-H system. The hydrogen absorption/desorption in TiZrNbHfTa is completely reversible and the activation energy of desorption could be calculated. Furthermore, we have observed an interesting macrostructure following parallel planes after the formation of the dihydride phase, which is retained after desorption.
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•Hydrogen absorption/desorption properties of the bcc TiZrNbHfTa high entropy alloy are reported.•TiZrNbHfTa absorbs hydrogen forming a fcc dihydride with an intermediate tetragonal monohydride.•The hydrogen absorption/desorption is completely reversible.•An interesting macrostructure following parallel planes is observed for the dihydride phase.
STUDY QUESTION
What are the results of transplanting cryopreserved ovarian tissue?
SUMMARY ANSWER
The transplanted ovarian tissue can last up to 10 years, with no relapses following the 53 ...transplantations, and the chance of a successful pregnancy is currently around one in three for those with a pregnancy-wish.
WHAT IS KNOWN ALREADY
Cryopreservation of ovarian tissue is now gaining ground as a valid method for fertility preservation. More than 36 children worldwide have now been born following this procedure.
STUDY DESIGN, SIZE, DURATION
This is a retrospective cohort study of 41 women who had thawed ovarian tissue transplanted 53 times over a period of 10 years, including 1 patient who was lost to follow-up.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The 41 Danish women, who had in total 53 transplantations, were followed for ovarian function and fertility outcome. Safety was assessed by monitoring relapse in cancer survivors.
MAIN RESULTS, AND THE ROLE OF CHANCE
Among 32 women with a pregnancy-wish, 10 (31%) had a child/children (14 children in total); this included 1 woman with a third trimester on-going pregnancy. In addition, two legal abortions and one second trimester miscarriage occurred. A total of 24 clinical pregnancies were established in the 32 women with a pregnancy-wish. The tissue remained functional for close to 10 years in some cases and lasted only a short period in others. Three relapses occurred but were unlikely to be due to the transplanted tissue.
LIMITATIONS, REASONS FOR CAUTION
Self-report through questionnaires with only in-one hospital formalised follow-up of transplanted patients could result in unreported miscarriages. The longevity of the tissue may vary by few months compared with those reported because some patients simply could not remember the date when the tissue became non-functional.
WIDER IMPLICATIONS OF THE FINDINGS
Cryopreservation of ovarian tissue is likely to become integrated into the treatment of young women, with cancer, who run a risk of losing their fertility. The full functional lifespan of grafts is still being evaluated, because many of the transplanted women have continued to maintain ovarian activity. Some of our first cases have had tissue functioning for ∼10 years.
STUDY FUNDING/COMPETING INTEREST(S)
The Child Cancer Foundation in Denmark (2012–26) and the EU interregional project ReproHigh are thanked for having funded this study. They had no role in the study design, collection and analysis of data, data interpretation or writing of the report. The authors have no conflict of interest to disclose.
BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to ...update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
Background
Patients with systemic mastocytosis (SM) may suffer from mast cell (MC) mediator‐related symptoms insufficiently controlled by conventional therapy. Omalizumab is an established treatment ...in other MC‐driven diseases, but experiences in SM are limited.
Objective
To assess the efficacy and safety of omalizumab in SM.
Methods
In our patient cohort, we evaluated all SM patients treated with omalizumab. A physician global assessment of type and severity of symptoms was performed at baseline, at 3 and 6 months and at latest follow‐up. Quality of life was assessed by visual analogue scale. S‐tryptase and KIT D816V allele burden were monitored.
Results
A total of 14 adult SM patients (10 ISM, 2 BMM, 1 SSM, and 1 ASM‐AHN) received omalizumab with a median duration of 17 months (range: 1‐73 months). One patient was excluded due to concomitant cytoreductive therapy. In the remaining 13 patients, we observed a significant reduction in symptoms, with complete symptom control in five (38.5%), major response in three (23.1%), and a partial response in three (23.1%) patients, whereas two patients (15.4%) withdrew due to subjective side‐effects at first dose. The treatment was most effective for recurrent anaphylaxis and skin symptoms, less for gastrointestinal, musculoskeletal, and neuropsychiatric symptoms. Patient‐reported quality of life showed significant improvement. No significant changes in s‐tryptase/KIT D816V allele burden were observed. No severe adverse events were recorded.
Conclusions
Omalizumab appears to be a promising treatment option in SM, effectively preventing anaphylaxis and improving chronic MC mediator‐related symptoms, insufficiently controlled by conventional therapy. Controlled studies are needed to substantiate findings.
The transmission success of free-living larval stages of endohelminths is generally modulated by a variety of abiotic and biotic environmental factors. Whereas the role of abiotic factors (including ...anthropogenic pollutants) has been in focus in numerous studies and summarized in reviews, the role of biotic factors has received much less attention. Here, we review the existing body of literature from the fields of parasitology and ecology and recognize 6 different types of biotic factors with the potential to alter larval transmission processes. We found that experimental studies generally indicate strong effects of biotic factors, and the latter emerge as potentially important, underestimated determinants in the transmission ecology of free-living endohelminth stages. This implies that biodiversity, in general, should have significant effects on parasite transmission and population dynamics. These effects are likely to interact with natural abiotic factors and anthropogenic pollutants. Investigating the interplay of abiotic and biotic factors will not only be crucial for a thorough understanding of parasite transmission processes, but will also be a prerequisite to anticipate the effects of climate and other global changes on helminth parasites and their host communities.
Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, ...impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score-the IntelliSep Index (ISI)-that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics-the aspect ratio and visco-elastic inertial response-that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass ...grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial.
The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651.
Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 95% CI 1·24–2·01); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 95% CI 0·74–1·59; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 95% CI 1·66–5·39; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 95% CI 1·25–2·40; p=0·0009).
In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation.
Biosensors.
We investigated the role of the chondrocyte primary cilium in mechanotransduction events related to cartilage extracellular matrix synthesis. We generated conditionally immortalized wild‐type (WT) ...and IFT88orpk (ORPK) mutant chondrocytes that lack primary cilia and assessed intracellular Ca2+ signaling, extracellular matrix synthesis, and ATP release in response to physiologically relevant compressive strains in a 3‐dimensional chondrocyte culture system. All conditions were compared to unloaded controls. We found that cilia were required for compression‐induced Ca2+ signaling mediated by ATP release, and an associated up‐regulation of aggrecan mRNA and sulfated glycosaminosglycan secretion. However, chondrocyte cilia were not the initial mechanoreceptors, since both WT and ORPK cells showed mechanically induced ATP release. Rather, we found that primary cilia were required for downstream ATP reception, since ORPK cells did not elicit a Ca2+ response to exogenous ATP even though WT and ORPK cells express similar levels of purine receptors. We suggest that purinergic Ca2+ signaling may be regulated by polycystin‐1, since ORPK cells only expressed the C‐terminal tail. This is the first study to demonstrate that primary cilia are essential organelles for cartilage mechanotransduction, as well as identifying a novel role for primary cilia not previously reported in any other cell type, namely cilia‐mediated control of ATP reception.—Wann, A. K. T., Zuo, N., Haycraft, C. J., Jensen, C. G., Poole, C. A., McGlashan, S. R., Knight, M. M. Primary cilia mediate mechanotransduction through control of ATP‐induced Ca2+ signaling in compressed chondrocytes. FASEB J. 26, 1663‐1671 (2012). www.fasebj.org
Background
Repair of an umbilical hernia is most often considered the less important condition when concomitant with other abdominal surgery. Despite this, the evidence for a concomitant umbilical ...hernia repair is sparse. The aim of this nationwide cohort study is to compare the short- and long-term outcomes of primary umbilical hernia repair and umbilical hernia repair concomitant with other abdominal surgery.
Method
Data from the Danish Hernia Database and the National Patients Registry from January 2007 to December 2018 was merged, resulting in identification of patients receiving umbilical hernia concomitant to another abdominal surgery (laparoscopic inguinal hernia repair, laparoscopic cholecystectomy, and laparoscopic appendectomy). This group was propensity score matched with patients undergoing umbilical hernia repair as a primary procedure. Outcome data included 90-day readmission, 90-day reoperation, and operation for recurrence.
Results
A total of 3365 primary umbilical hernia repairs and 2418 umbilical hernia repairs concomitant to other abdominal surgery were included. Readmission (10.5%, 255/2418) and reoperation (3.8%, 93/2418) rates within 90 days were decreased for umbilical hernia repairs concomitant to other abdominal surgery, compared with primary umbilical hernia repairs (22.7%, 765/3365) and (10.5%, 255/3365),
P
< 0.001 and
P
< 0.001, respectively. The rate of operation for recurrence was significantly increased for primary repairs (4.2%, 141/3365), compared with repairs concomitant to other abdominal surgery (3.2%, 77/2418),
P
= 0.014.
Conclusion
Outcome in umbilical hernia repair performed concomitant to laparoscopic inguinal hernia repair, elective or emergency laparoscopic cholecystectomy, or laparoscopic appendectomy is comparable to umbilical hernia repair without concomitant surgery.
Abstract
STUDY QUESTION
How are temporal trends in lifestyle factors, including exposure to maternal smoking in utero, associated to semen quality in young men from the general population?
SUMMARY ...ANSWER
Exposure to maternal smoking was associated with lower sperm counts but no overall increase in sperm counts was observed during the study period despite a decrease in this exposure.
WHAT IS KNOWN ALREADY
Meta-analyses suggest a continuous decline in semen quality but few studies have investigated temporal trends in unselected populations recruited and analysed with the same protocol over a long period and none have studied simultaneous trends in lifestyle factors.
STUDY DESIGN, SIZE, DURATION
Cross-sectional population-based study including ~300 participants per year (total number = 6386) between 1996 and 2016.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The study is based on men from the Greater Copenhagen area, Denmark, with a median age of 19 years, and unselected with regard to fertility status and semen quality. The men delivered a semen sample, had a blood sample drawn and a physical examination performed and answered a comprehensive questionnaire, including information on lifestyle and the mother's pregnancy. Temporal trends in semen quality and lifestyle were illustrated graphically, and trends in semen parameters and the impact of prenatal and current lifestyle factors were explored in multiple regression analyses.
MAIN RESULTS AND THE ROLE OF CHANCE
Throughout the study period, 35% of the men had low semen quality. Overall, there were no persistent temporal trends in semen quality, testicular volume or levels of follicle-stimulating hormone over the 21 years studied. The men's alcohol intake was lowest between 2011 and 2016, whereas BMI, use of medication and smoking showed no clear temporal trends. Parental age increased, and exposure in utero to maternal smoking declined from 40% among men investigated in 1996-2000 to 18% among men investigated in 2011-2016. Exposure to maternal smoking was associated with lower sperm counts but no overall increase in sperm counts was observed despite the decrease in this exposure.
LIMITATIONS, REASONS FOR CAUTION
Information of current and prenatal lifestyle was obtained by self-report, and the men delivered only one semen sample each.
WIDER IMPLICATIONS OF THE FINDINGS
The significant decline in in utero exposure to maternal smoking, which was not reflected in an overall improvement of semen quality at the population level, suggest that other unknown adverse factors may maintain the low semen quality among Danish men.
STUDY FUNDING/COMPETING INTEREST(S)
The study has received financial support from the ReproUnion; 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); the Danish Ministry of Health; the Danish Environmental Protection Agency; A.P. Møller and wife Chastine McKinney Møllers foundation; and Svend Andersens Foundation. None of the funders had any role in the study design, collection, analysis or interpretation of data, writing of the paper or publication decisions.
TRIAL REGISTRATION NUMBER
N/A.
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