A balancing act: sex selection after pre-implantation genetic testing for aneuploidy for first versus second baby.

STUDY QUESTION: How often do patients undergoing frozen embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) choose to select for sex and do sex selection rates differ before and after successful delivery of a first baby? SUMMARY ANSWER: When a choice was available between male and female embryos, patients selected the sex more frequently when trying to conceive the second child (62%) as compared to the first child (32.4%) and most commonly selected for the opposite sex of the first child. WHAT IS KNOWN ALREADY: Sex selection is widely available in US fertility clinics. However, the rate of sex selection for patients undergoing FET after PGT-A is unknown. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of 585 patients that took place between January 2013 and February 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study took place at a single, urban academic fertility center in the USA. Patients were included if they had a live birth after single euploid FET and returned for at least one subsequent euploid FET. The primary outcomes were the rates of sex selection for first versus second baby. Secondary outcomes were rate of selection for same versus opposite sex as first live birth and overall rate of selection for males versus females. MAIN RESULTS AND THE ROLE OF CHANCE: Five hundred and eighty-five patients underwent a total of 1560 single euploid FETs resulting in either one or two live births. A choice between male and female euploid embryos was available for 919 FETs (first child: 67.5% (519/769) versus second child: 50.6% (400/791), P < 0.01). When a choice was available, patients selected the sex more frequently when trying to conceive the second child (first child: 32.4% (168/519) versus second child: 62.0% (248/400), P < 0.01). When sex was selected after first live birth, the opposite sex of the first child was selected 81.8% (203/248 FETs) of the time. Of transfers that involved sex selection, rates of male and female selection were similar for the first child, but selection for females was greater for the second child (first child: 51.2% (86/168) male versus 48.9% (82/168) female, second child: 41.1% (102/248) male versus 58.9% (146/248) female, P < 0.04). LIMITATIONS, REASONS FOR CAUTION: The study was performed at one urban academic medical center in the Northeastern US, which may limit generalizability to other settings where PGT-A may be performed less frequently, or sex selection may be limited or not permitted. In addition, we could not reliably account for whether patients or their partners had prior children and if so, of what sex. WIDER IMPLICATIONS OF THE FINDINGS: Patients undergoing PGT-A with both male and female euploid embryos were more likely to select for sex when attempting a second child and usually selected for the opposite sex of their first child. These findings highlight the potential for family balancing for patients who undergo PGT-A in settings where sex selection is permitted. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Biological interactions mediate context and species-specific sensitivities to salinity.

Toxicants have both sub-lethal and lethal effects on aquatic biota, influencing organism fitness and community composition. However, toxicant effects within ecosystems may be altered by interactions with abiotic and biotic ecosystem components, including biological interactions. Collectively, this generates the potential for toxicant sensitivity to be highly context dependent, with significantly different outcomes in ecosystems than laboratory toxicity tests predict. We experimentally manipulated stream macroinvertebrate communities in 32 mesocosms to examine how communities from a low-salinity site were influenced by interactions with those from a high-salinity site along a gradient of salinity. Relative to those from the low-salinity site, organisms from the high-salinity site were expected to have greater tolerance and fitness at higher salinities. This created the potential for both salinity and tolerant-sensitive organism interactions to influence communities. We found that community composition was influenced by both direct toxicity and tolerant-sensitive organism interactions. Taxon and context-dependent responses included: (i) direct toxicity effects, irrespective of biotic interactions; (ii) effects that were owing to the addition of tolerant taxa, irrespective of salinity; (iii) toxicity dependent on sensitive-tolerant taxa interactions; and (iv) toxic effects that were increased by interactions. Our results reinforce that ecological processes require consideration when examining toxicant effects within ecosystems.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.

A comparison of the incidence of undiagnosed congenital heart disease in hospital born and home born children.

OBJECTIVE: To evaluate the incidence of otherwise undiagnosed congenital heart disease (CHD) in a population of children born in a hospital with routine pulse oximetry (RPO) screening compared to children born at home. METHODS: We reviewed 15 years of births at 2 hospitals for incidence of undiagnosed CHD with RPO. The Health Department reviewed the same data for out of hospital births. RESULTS: A total of 50,545 hospital births were screened and 1,274 children were born outside the hospital. There were 28 hospital-born babies diagnosed with cyanotic CHD prior to nursery discharge. Only one of these babies would not have been diagnosed without RPO. Three children were missed and there were 3 false positives. Sensitivity and positive predictive value of RPO was 25%, specificity and negative predictive value of RPO exceed 99%. The incidence of CHD requiring RPO diagnosis was roughly one birth per 50,000. Two children born at home with undiagnosed CHD were missed. One of these children presented with neonatal demise. CONCLUSION: RPO screening is still valuable in diagnosing CHD only diagnosable with RPO. However, the incidence of CHD requiring RPO to diagnose is similar to other congenital diseases which are not mandated national screening tests. In our limited experience a patient is roughly 25 times more likely to have undiagnosed CHD if they are born outside of a hospital.

Temporal Dynamics of Botrytis cinerea and Sclerotinia sclerotiorum in Seed Alfalfa Fields of Southern Alberta, Canada.

Blossom blight of seed alfalfa (Medicago sativa L.), caused by the fungal pathogens Botrytis cinerea and Sclerotinia sclerotiorum, is a potentially devastating disease on the Canadian Prairies in moist growing seasons. Monitoring the airborne spore concentrations of these pathogens could facilitate disease forecasting in the region. Nineteen seed alfalfa fields in southern Alberta, Canada were assessed throughout the growing seasons of 2014 and 2015. Trace levels of blossom blight symptoms were found in both years; however, plated floret and pod samples indicated that, overall, B. cinerea increased over the growing season whereas S. sclerotiorum decreased. In both seasons, Burkard 7-day volumetric spore samplers collected daily aerosol samples, and weather stations recorded environmental variables in three fields. Conidia and ascospores collected were quantified each day with a real-time polymerase chain reaction assay. Spore quantification indicated that both B. cinerea and S. sclerotiorum numbers remained low in July and increased in August. Both species had multiple days with high spore discharge, with seasonal maxima of 21,137 conidia and 2,265 ascospores. Exploratory model development indicated that spore discharge of both fungi is associated with environmental stressors such as large changes in relative humidity or high temperatures on preceding days.

A multiplex PCR assay for the detection and quantification of Sclerotinia sclerotiorum and Botrytis cinerea.

UNLABELLED: Traditional culture methods for identifying the plant fungal pathogens Sclerotinia sclerotiorum (Lib.) de Bary and Botrytis cinerea Pers.:Fr. are slow and laborious. The goal of this study was to develop a multiplex real-time PCR (qPCR) assay to detect and quantify DNA from S. sclerotiorum and B. cinerea. A primer set (SsIGS_5) for S. sclerotiorum was designed that targeted the intergenic spacer (IGS) regions of the ribosomal DNA. Addition of a probe to the assay increased its specificity: when the primer/probe set was tested against 21 fungal species (35 strains), amplification was detected from all S. sclerotiorum strains and no other species. For qPCR, the SsIGS_5 primer and probe set exhibited a linear range from 7·0 ng to 0·07 pg target DNA (R(2)  = 0·99). SsIGS_5 was then multiplexed with a previously published primer/probe set for B. cinerea to develop a high-throughput method for the detection and quantification of DNA from both pathogens. When multiplexed, the sensitivity and specificity of both assays were not different from individual qPCR reactions. The multiplex assay is currently being used to detect and quantify S. sclerotiorum and B. cinerea DNA from aerosol samples collected in commercial seed alfalfa fields. SIGNIFICANCE AND IMPACT OF THE STUDY: A primer and probe set for the quantification of Sclerotinia sclerotiorum DNA in a PCR assay was developed. The probe-based nature of this assay signifies an improvement over previous assays for this species by allowing multiplex reactions while maintaining high sensitivity. The primer/probe set was used in a multiplex real-time PCR assay for the quantification of S. sclerotiorum and Botrytis cinerea DNA, enabling rapid analysis of environmental samples. In crops susceptible to both pathogens, this multiplex assay can be used to quickly quantify the presence of each pathogen.

[Preclinical evaluation of coated knee implants for allergic patients]. / Präklinische Ergebnisse beschichteter Knieimplantate für Allergiker.

BACKGROUND: 10-15% of the population show allergic reactions against skin contact to metals as nickel, cobalt or chromium and have thus a risk of not tolerating implants containing those materials. The relationship between periimplantary hypersensivity reaction and given cutaneous contact allergy is currently unknown. A new developed multilayer coating system is supposed to prevent long-term allergic reactions that may result from uncoated implants. METHODS: Stability and function (concerning bonding durability, wear and ion release to the serum) of the multilayer coating system has been examined in a test series. RESULTS: The specific architecture of the multilayer coating system evidences a very good bonding durability. The results of the test in the simulator show a reduction of wear of approximately 60% compared to the uncoated implants. Ion concentrations within the serum of the wear tests were by magnitudes lower than those measured in reference tests on uncoated components. CONCLUSION: The results of the preclinical evaluation prove that the durability and function of the multilayer coating system are as intended.

The reliability of a single pulse oximetry reading as a screening test for congenital heart disease in otherwise asymptomatic newborn infants.

Routine pulse oximetry has been studied to detect children with otherwise undiagnosed congenital heart disease prior to nursery discharge. The reported sensitivities in asymptomatic patients have been less than expected and vary widely, bringing into question the reliability of the test. The purpose of this study was to assess whether routine pulse oximetry contributes to identifying patients with critical congenital heart disease and to determine the reliability of a single pulse oximeter reading in screening asymptomatic newborn infants. Between December 26, 2003, and December 31, 2005, three hospitals in west central Florida performed a pulse oximetry routinely on all newborns at the time of discharge. Patients diagnosed with critical congenital heart disease during the study period were identified to assess whether the pulse oximetry reading initiated their diagnosis. In one hospital, the pulse oximeter data were evaluated for reliability. Downloaded data were compared to a log compiled by the nursery personnel, first without (phase 1) and then with (phase 2) their knowledge and additional training. Results were characterized as reliable, probe placed but reading not verifiable, or no evidence of probe placement. Of the 7962 infants who received oximetry testing, there were 12 postnatal diagnoses of critical congenital heart disease. None was initially identified by routine pulse oximetry. Pulse oximetry reliability improved substantially between phase 1 and phase 2 (38 v. 60%, p < 0.0001). Optimal reliability (>95%) was obtained by a nurse with a degree of LPN or higher performing an assessment of at least 360 seconds. Routine pulse oximetry was neither reliable nor an important diagnostic tool in our cohort. Important human factors (probe placement time, oximetry training, and nursing degree) impact single determination pulse oximetry reliability. With routine surveillance and quality improvement, the reliability of this test can be increased. Future studies to determine the effectiveness of pulse oximetry screening for the diagnosis of congenital heart disease in the asymptomatic newborn population must address these factors. Until such a study demonstrates acceptable sensitivity and clinical value, universal screening should not be instituted.

A critical appraisal of overdiagnosis: estimates of its magnitude and implications for lung cancer screening.

BACKGROUND: The magnitude of overdiagnosis is a critical and unresolved issue in lung cancer (LC) screening:(1) its contribution to the increase in survival constitutes specious evidence of benefit;(2) overdiagnosed individuals who undergo resection will experience a reduction in life expectancy, partially or completely offsetting the benefit received by others in whom earlier intervention proves curative. METHOD: Critical analysis of studies in opposition and support of the view that LC screening imposes a substantial burden of overdiagnosis. RESULTS: Approximately 25%, possibly more, of radiographically (chest x ray) diagnosed LC appears to be overdiagnosed. Based on the observed tumour volume doubling time of low dose CT identified small malignant pulmonary nodules, CT will markedly augment lead time, increasing exposure to competing lethal morbidities, thereby increasing overdiagnosis. CONCLUSION: To reduce all-cause mortality, CT screening will need to reduce LC mortality by an amount that exceeds the increase in mortality attributable to surgery and loss of pulmonary reserve in persons who are overdiagnosed or pathologically understaged (ie, with occult micrometastases). Presently, there is no evidence that CT screening will achieve any reduction in LC mortality.

Reliability of a single pulse oximetry reading as a screening test for congenital heart disease in otherwise asymptomatic newborn infants: the importance of human factors.

BACKGROUND: The use of routine pulse oximetry to detect neonates with undiagnosed congenital heart disease before nursery discharge has been studied. The reported sensitivities with asymptomatic patients have been less than expected and vary widely, bringing into question the reliability of the test. This study aimed to assess whether routine pulse oximetry contributes to identifying patients with critical congenital heart disease, and to determine the reliability of a single pulse oximeter reading for screening asymptomatic newborn infants. METHODS: Between December 26, 2003 and December 31, 2005, three hospitals in west central Florida performed pulse oximetry routinely on all newborns at the time of discharge. Patients who received a diagnosis of critical congenital heart disease during the study period were identified to assess whether the pulse oximetry reading initiated their diagnosis. In one hospital, the pulse oximeter data were evaluated for reliability. Downloaded data were compared to a log compiled by the nursery personnel, first without (Phase 1) and then with (Phase 2) their knowledge and additional training. The results were characterized as reliable, probe placed but reading not verifiable, or no evidence of probe placement. RESULTS: Among the 7,962 infants who received oximetry testing, there were 12 postnatal diagnoses of critical congenital heart disease. None was initially identified by routine pulse oximetry. Pulse oximetry reliability improved substantially between Phases 1 and 2 (38% vs 60%; p < 0.0001). Optimal reliability (>95%) was obtained by a nurse with a licensed practical nurse degree or higher performing an assessment of at least 360 s. CONCLUSION: Routine pulse oximetry was neither reliable nor an important diagnostic tool for our cohort. Important human factors (probe placement time, oximetry training, and nursing degree) have an impact on single-determination pulse oximetry reliability. With routine surveillance and quality improvement, the reliability of this test can be increased. Future studies to determine the effectiveness of pulse oximetry screening for the diagnosis of congenital heart disease in the asymptomatic newborn population must address these factors. Until such a study demonstrates acceptable sensitivity and clinical value, universal screening should not be instituted.

The Helmholtz Network for Bioinformatics: an integrative web portal for bioinformatics resources.

SUMMARY: The Helmholtz Network for Bioinformatics (HNB) is a joint venture of eleven German bioinformatics research groups that offers convenient access to numerous bioinformatics resources through a single web portal. The 'Guided Solution Finder' which is available through the HNB portal helps users to locate the appropriate resources to answer their queries by employing a detailed, tree-like questionnaire. Furthermore, automated complex tool cascades ('tasks'), involving resources located on different servers, have been implemented, allowing users to perform comprehensive data analyses without the requirement of further manual intervention for data transfer and re-formatting. Currently, automated cascades for the analysis of regulatory DNA segments as well as for the prediction of protein functional properties are provided. AVAILABILITY: The HNB portal is available at http://www.hnbioinfo.de

PRECIS: protein reports engineered from concise information in SWISS-PROT.

MOTIVATION: There have been several endeavours to address the problem of annotating sequence data computationally, but the task is non-trivial and few tools have emerged that gather useful information on a given sequence, or set of sequences, in a simple and convenient manner. As more genome projects bear fruit, the mass of uncharacterized sequence data accumulating in public repositories grows ever larger. There is thus a pressing need for tools to support the process of automatic analysis and annotation of newly determined sequences. With this in mind, we have developed PRECIS, which automatically creates protein reports from sets of SWISS-PROT entries, collating results into structured reports, detailing known biological and medical information, literature and database cross-references, and relevant keywords.

Is the unitarity of the quark-mixing CKM matrix violated in neutron beta-decay?

We report on a new measurement of neutron beta-decay asymmetry. From the result A(0) = -0.1189(7), we derive the ratio of the axial vector to the vector coupling constant lambda = g(A)/g(V) = -1.2739(19). When included in the world average for the neutron lifetime tau = 885.7(7) s, this gives the first element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix V(ud). With this value and the Particle Data Group values for V(us) and V(ub), we find a deviation from the unitarity condition for the first row of the CKM matrix of Delta = 0.0083(28), which is 3.0 times the stated error.

[Acute fatty liver in pregnancy: clinical and histopathological course. Case report]. / Akute Schwangerschaftsfettleber: Klinischer und histopathologischer Verlauf. Kasuistik

Acute fatty liver of pregnancy is a rare disease which may be letal if diagnosis is missed. The pathogenesis is not completely clear, but there is some evidence that some cases have been associated with a genetic deficiency of fatty acid beta-oxidation. Other predisposing factors include primiparity, multiple pregnancy, male fetal sex and pre-eclampsia. Clinical presentation and laboratory findings are often unspecific. Increasing serum aminotransferases are characteristic in the early stage of the disease. Liver biopsy establishes the diagnosis and typically shows microvesicular, centrilobular fatty changes of hepatocytes. Differential diagnosis includes the HELLP-Syndrome, cholestasis of pregnancy, pre-eclampsia and viral or drug induced hepatitis. Without adequate treatment liver failure with coagulopathy and encephalopathy may develop. Two cases of acute fatty liver in pregnancy in an early stage are presented. Clinical and histopathological findings as well as diagnostic and therapeutic procedures are discussed.

Vulnerability to stress among women in chronic pain from fibromyalgia and osteoarthritis.

In two investigations, we studied vulnerability to the negative effects of stress among women in chronic pain from 2 types of musculoskeletal illnesses, fibromyalgia syndrome (FMS) and osteoarthritis (OA). In Study 1, there were 101 female participants 50 to 78 years old: 50 had FMS, 29 had OA knee pain and were scheduled for knee surgery, and 22 had OA but were not planning surgery. Cross-sectional analyses showed that the three groups were comparable on demographic variables, personality attributes, negative affect, active coping, and perceived social support. As expected, FMS and OA surgery women reported similar levels of bodily pain, and both groups scored higher than OA nonsurgery women. However, women with FMS reported poorer emotional and physical health, lower positive affect, a poorer quality social milieu, and more frequent use of avoidant coping with pain than did both groups of women with OA. Moreover, the perception and use of social support were closely tied to perceived social stress only among the FMS group. In Study 2, we experimentally manipulated negative mood and stress in 41 women 37 to 74 years old: 20 women had FMS, and 21 women had OA. Participantsfrom each group were randomly assigned to either a negative mood induction or a neutral mood (control) condition, and then all participants discussed a stressful interpersonal eventfor 30 min. Stress-related increases in pain were exacerbated by negative mood induction among women with FMS but not women with OA, and pain during stress was associated with decreases in positive affect in women with FMS but not women with OA. These findings suggest that among women with chronic pain, those with FMS may be particularly vulnerable to the negative effects of social stress. They have fewer positive affective resources, use less effective pain-coping strategies, and have more constrained social networks than their counterparts with OA, particularly those who experience similar levels ofpain. They also seem to experience more prolonged stress-related increases in pain under certain circumstances, all of which may contribute to a lowering of positive affect and increased stress reactivity over time.