L-shell spectroscopy of neon and fluorine like copper ions from laser produced plasma

Ne, F, and O-like Rydberg resonance lines along with some of the inner shell satellite lines of Copper plasma, in the wavelength range of 7.9-9.5 Å, are experimentally observed using a thallium acid phthalate crystal spectrometer. The plasma is produced by the irradiation of a Cu target with a 15 J, 500 ps Nd: Glass laser with a focusable intensity up to 5 × 10 14 W/cm 2 . The observed lines result from the transitions among 2p-nd, 2p-ns, and 2s-nd (n = 4-6) levels. Transition wavelengths, transition probabilities, and oscillator strengths of these lines are calculated using the Multi-Configuration Dirac-Fock method. In this computation, the contribution of relativistic corrections such as two-body Breit corrections and QED corrections due to vacuum polarization and self-energy has also been considered. FLYCHK simulations are used to analyze the distribution of the various charge states of the Copper ions and to find the temperature and density of plasma. Moreover, the effect of self-absorption of the plasma (opacity), as well as of suprathermal electrons on charge state distribution of ions, is also studied. The synthetic spectrum provides a best-match with the experimental spectrum at a laser intensity of 1.3 × 10 14 W/cm 2 for T c = 150 eV, T h = 1000 eV, f = 0.008, and density 4.5 × 10 20 cm −3 .The temperature and density ranges are also calculated using a radiative hydrodynamic code. The calculated temperature and density range are in agreement with the experimentally determined values. The effect of the change in laser intensity on the L-shell spectrum of Cu is studied which indicates the switching between lower (Cu XX) and higher charge states (Cu XXI and Cu XXII) at higher laser intensities

Understanding the role of intersectoral convergence in the delivery of essential maternal and child nutrition interventions in Odisha, India: a qualitative study.

BACKGROUND: Convergence of sectoral programs is important for scaling up essential maternal and child health and nutrition interventions. In India, these interventions are implemented by two government programs - Integrated Child Development Services (ICDS) and National Rural Health Mission (NRHM). These programs are designed to work together, but there is limited understanding of the nature and extent of coordination in place and needed at the various administrative levels. Our study examined how intersectoral convergence in nutrition programming is operationalized between ICDS and NRHM from the state to village levels in Odisha, and the factors influencing convergence in policy implementation and service delivery. METHODS: Semi-structured interviews were conducted with state-level stakeholders (n = 12), district (n = 19) and block officials (n = 66), and frontline workers (FLWs, n = 48). Systematic coding and content analysis of transcripts were undertaken to elucidate themes and patterns related to the degree and mechanisms of convergence, types of actions/services, and facilitators and barriers. RESULTS: Close collaboration at state level was observed in developing guidelines, planning, and reviewing programs, facilitated by a shared motivation and recognized leadership for coordination. However, the health department was perceived to drive the agenda, and different priorities and little data sharing presented challenges. At the district level, there were joint planning and review meetings, trainings, and data sharing, but poor participation in the intersectoral meetings and limited supervision. While the block level is the hub for planning and supervision, cooperation is limited by the lack of guidelines for coordination, heavy workload, inadequate resources, and poor communication. Strong collaboration among FLWs was facilitated by close interpersonal communication and mutual understanding of roles and responsibilities. CONCLUSIONS: Congruent or shared priorities and regularity of actions between sectors across all levels will likely improve the quality of coordination, and clear roles and leadership and accountability are imperative. As convergence is a means to achieving effective coverage and delivery of services for improved maternal and child health and nutrition, focus should be on delivering all the essential services to the mother-child dyads through mechanisms that facilitate a continuum of care approach, rather than sectorally-driven, service-specific delivery processes

Lipoprotein(a) is associated with a larger systemic burden of arterial calcification

AIMS: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. However, population-based evidence on the link between Lp(a) and subclinical arteriosclerosis is lacking. We assessed associations of Lp(a) concentrations with arteriosclerosis in multiple arteries. METHODS AND RESULTS: From the population-based Rotterdam study, 2354 participants (mean age: 69.5 years, 52.3% women) underwent non-contrast computed tomography to assess arterial calcification as a hallmark of arteriosclerosis. We quantified the volume of coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC), and intracranial carotid artery calcification (ICAC). All participants underwent blood sampling, from which plasma Lp(a) concentrations were derived. The association of plasma Lp(a) levels was assessed with calcification volumes and with severe calcification (upper quartile of calcification volume) using sex-stratified multivariable linear and logistic regression models. Higher Lp(a) levels were associated with larger ln-transformed volumes of CAC [fully adjusted beta 95% confidence interval (CI) per 1 standard deviation (SD) in women: 0.09, 95% CI 0.04-0.14, men: 0.09, 95% CI 0.03-0.14], AAC (women: 0.06, 95% CI 0.01-0.11, men: 0.09, 95% CI 0.03-0.14), ECAC (women: 0.07, 95% CI 0.02-0.13, men: 0.08, 95% CI 0.03-0.14), and ICAC (women: 0.09, 95% CI 0.03-0.14, men: 0.05, 95% CI -0.02 to 0.11]. In the highest Lp(a) percentile, severe ICAC was most prevalent in women [fully adjusted odds ratio (OR) 2.41, 95% CI 1.25-4.63] and severe AAC in men (fully adjusted OR 3.29, 95% CI 1.67-6.49). CONCLUSION: Higher Lp(a) was consistently associated with a larger calcification burden in all major arteries. The findings of this study indicate that Lp(a) is a systemic risk factor for arteriosclerosis and thus potentially an effective target for treatment. Lp(a)-reducing therapies may reduce the burden from arteriosclerotic events throughout the arterial system. TRANSLATIONAL PERSPECTIVE: In 2354 participants from the Rotterdam study, we assessed the link between Lp(a) concentrations and arterial calcifications, as proxy for arteriosclerosis, in major arteries. We found that higher Lp(a) levels were consistently associated with larger volumes of calcification in the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. The findings of our study indicate that Lp(a) is a systemic risk factor for arteriosclerosis, suggesting that the systemic burden of arteriosclerosis throughout the arterial system could be reduced by targeting Lp(a).</p

Sex difference in the incidence of microvascular complications in patients with type 2 diabetes mellitus: a prospective cohort study

Aims: Type 2 diabetes mellitus is a major cause of death and disability due to its long-term macro- and microvascular diseases. Although women with type 2 diabetes have more macrovascular diseases, it is unclear whether there are sex differences in the occurrence of microvascular disease. The aim of our study was to investigate sex differences in the incidence of microvascular complications in type 2 diabetes. Methods: Analyses were performed in the DiaGene study, a prospective cohort study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886, mean follow-up time = 6.93 years). Cox proportional hazard models adjusted for risk factors for complications (age, smoking, hypertension, dyslipidemia, HbA1c and duration of type 2 diabetes) were used to analyze the incidence of microvascular complications in men and women. Results: The incidence of microalbuminuria was significantly higher in men (HR microalbuminuria 1.64 [CI 1.21–2.24], p = 0.002). Additionally, men are more likely to develop two or three microvascular complications compared to women (OR 2.42 [CI 1.69–3.45], p < 0.001). Conclusions: This study shows that men with type 2 diabetes are more likely to develop microvascular complications, especially microalbuminuria. Furthermore, men seem to have a higher chance of developing multiple microvascular complications. Our results highlight that men and women may not benefit to a similar extent from current treatment approaches to prevent diabetes-related microvascular diseases

The effect of guideline revisions on vascular complications of type 2 diabetes

Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study (n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend < 0.001). Conclusions: The introduction of the first diabetes guideline and subsequent revisions have reduced the risk of macrovascular and microvascular complications of type 2 diabetes, most strongly in diabetic retinopathy. This indicates that real-time diabetes care has improved over time

Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus

Aims/hypothesis: Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods: Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). Results: No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation: Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications

Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy

This study aimed to determine the prevalence of APC-associated familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) in a large cohort, taking into account factors as adenoma count and year of diagnosis. All application forms used to send patients in for APC and MUTYH variant analysis between 1992 and 2017 were collected (n = 2082). Using the data provided on the application form, the APC and biallelic MUTYH prevalence was determined and possible predictive factors were examined using multivariate multinomial logistic regression analysis in SPSS. The prevalence of disease causing variants in the APC gene significantly increases with adenoma count while MAP shows a peak prevalence in individuals with 50–99 adenomas. Logistic regression analysis shows significant odds ratios for adenoma count, age at diagnosis, and, interestingly, a decline in the chance of finding a variant in either gene over time. Moreover, in 22% (43/200) of patients with FAP-related extracolonic manifestations a variant was identified. The overall detection rates are above 10% for patients with >10 adenomas aged 20 adenomas aged T variant in the tumor or a first-degree relative with >10 adenomas. Therefore, APC and MUTYH testing in patients with >10 adenomas aged 20 adenomas aged <70 is advised. Almost all FAP and MAP patients not meeting these criteria showed other characteristics that can be used as an indication to prompt genetic testing

A Novel and Critical Role for Oct4 as a Regulator of the Maternal-Embryonic Transition

Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage. Specifically, Oct4 has a novel and critical role in regulating genes that encode transcriptional and post-transcriptional regulators as early as the 2-cell stage. Our data suggest that the key function of Oct4 may be to switch the developmental program from one that is predominantly regulated by post-transcriptional control to one that depends on the transcriptional network. Further, we propose to rank candidate genes quantitatively based on the inter-embryo variation in their differential expression in response to Oct4 knockdown. Of over 30 genes analyzed according to this proposed paradigm, Rest and Mta2, both of which have established pluripotency functions in ESCs, were found to be the most tightly regulated by Oct4 at the 2-cell stage.We show that the Oct4-regulated gene set at the 1- to 2-cell stages of early embryo development is large and distinct from its established network in ESCs. Further, our experimental approach can be applied to dissect the gene regulatory network of Oct4 and other pluripotency regulators to deconstruct the dynamic developmental program in the early embryo

Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic association study in Europeans.

AIM: Rare genetic variants in the CUBN gene encoding the main albumin-transporter in the proximal tubule of the kidneys have previously been associated with microalbuminuria and higher urine albumin levels, also in diabetes. Sequencing studies in isolated proteinuria suggest that these variants might not affect kidney function, despite proteinuria. However, the relation of these CUBN missense variants to the estimated glomerular filtration rate (eGFR) is largely unexplored. We hereby broadly examine the associations between four CUBN missense variants and eGFR creatinine in Europeans with Type 1 (T1D) and Type 2 Diabetes (T2D). Furthermore, we sought to deepen our understanding of these variants in a range of single- and aggregate- variant analyses of other kidney-related traits in individuals with and without diabetes mellitus. METHODS: We carried out a genetic association-based linear regression analysis between four CUBN missense variants ( rs141640975, rs144360241, rs45551835, rs1801239) and eGFR creatinine (ml/min/1.73 m 2, CKD-EPI creatinine(2012), natural log-transformed) in populations with T1D (n ~ 3,588) or T2D (n ~ 31,155) from multiple European studies and in individuals without diabetes from UK Biobank (UKBB, n ~ 370,061) with replication in deCODE (n = 127,090). Summary results of the diabetes-group were meta-analyzed using the fixed-effect inverse-variance method. RESULTS: Albeit we did not observe associations between eGFR creatinine and CUBN in the diabetes-group, we found significant positive associations between the minor alleles of all four variants and eGFR creatinine in the UKBB individuals without diabetes with rs141640975 being the strongest (Effect=0.02, P eGFR_creatinine=2.2 × 10 -9). We replicated the findings for rs141640975 in the Icelandic non-diabetes population (Effect=0.026, P eGFR_creatinine=7.7 × 10 -4). For rs141640975, the eGFR creatinine-association showed significant interaction with albuminuria levels (normo-, micro-, and macroalbuminuria; p = 0.03). An aggregated genetic risk score (GRS) was associated with higher urine albumin levels and eGFR creatinine. The rs141640975 variant was also associated with higher levels of eGFR creatinine-cystatin C (ml/min/1.73 m 2, CKD-EPI 2021, natural log-transformed) and lower circulating cystatin C levels. CONCLUSIONS: The positive associations between the four CUBN missense variants and eGFR in a large population without diabetes suggests a pleiotropic role of CUBN as a novel eGFR-locus in addition to it being a known albuminuria-locus. Additional associations with diverse renal function measures (lower cystatin C and higher eGFR creatinine-cystatin C levels) and a CUBN-focused GRS further suggests an important role of CUBN in the future personalization of chronic kidney disease management in people without diabetes

Deep phenotyping and genomic data from a nationally representative study on dementia in India

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.Peer reviewe