Quality Of Antenatal Care In Rural Southern Tanzania: A Reality Check.

Counselling on the danger signs of unpredictable obstetric complications and the appropriate management of such complications are crucial in reducing maternal mortality. The objectives of this study were to identify gaps in the provision of ANC services and knowledge of danger signs as well as the quality of care women receive in case of complications. The study took place in the Rufiji District of Tanzania in 2008 and was conducted in seven health facilities. The study used (1) observations from 63 antenatal care (ANC) sessions evaluated with an ANC checklist, (2) self-assessments of 11 Health workers, (3) interviews with 28 pregnant women and (4) follow-up of 12 women hospitalized for pregnancy-related conditions.Blood pressure measurements and abdominal examinations were common during ANC visits while urine testing for albumin or sugar or haemoglobin levels was rare which was often explained as due to a lack of supplies. The reasons for measuring blood pressure or abdominal examinations were usually not explained to the women. Only 15/28 (54%) women were able to mention at least one obstetric danger sign requiring medical attention. The outcomes of ten complicated cases were five stillbirths and three maternal complications. There was a considerable delay in first contact with a health professional or the start of timely interventions including checking vital signs, using a partograph, and detailed record keeping. Linking danger signs to clinical and laboratory examination results during ANC with the appropriate follow up and avoiding delays in emergency obstetric care are crucial to the delivery of coordinated, effective care interventions

Association of HbA1c Values with Mortality and Cardiovascular Events in Diabetic Dialysis Patients. The INVOR Study and Review of the Literature

BACKGROUND: Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control. METHODS: We followed 78 patients with DM initiating dialysis treatment of the region of Vorarlberg in a prospective cohort study applying a time-dependent Cox regression analysis using all measured laboratory values for up to more than seven years. This resulted in 880 HbA(1c) measurements (with one measurement every 3.16 patient months on average) during the entire observation period. Non-linear P-splines were used to allow flexible modeling of the association with mortality and cardiovascular disease (CVD) events. RESULTS: We observed a decreased mortality risk with increasing HbA(1c) values (HR = 0.72 per 1% increase, p = 0.024). Adjustment for age and sex and additional adjustment for other CVD risk factors only slightly attenuated the association (HR = 0.71, p = 0.044). A non-linear P-spline showed that the association did not follow a fully linear pattern with a highly significant non-linear component (p = 0.001) with an increased risk of all-cause mortality for HbA(1c) values up to 6-7%. Causes of death were associated with HbA(1c) values. The risk for CVD events, however, increased with increasing HbA(1c) values (HR = 1.24 per 1% increase, p = 0.048) but vanished after extended adjustments. CONCLUSIONS: This study considered the entire information collected on HbA(1c) over a period of more than seven years. Besides the methodological advantages our data indicate a significant inverse association between HbA(1c) levels and all-cause mortality. However, for CVD events no significant association could be found

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Multiferroicity in an organic charge-transfer salt: Electric-dipole-driven magnetism

Multiferroics, showing simultaneous ordering of electrical and magnetic degrees of freedom, are remarkable materials as seen from both the academic and technological points of view. A prominent mechanism of multiferroicity is the spin-driven ferroelectricity, often found in frustrated antiferromagnets with helical spin order. There, similar to conventional ferroelectrics, the electrical dipoles arise from an off-centre displacement of ions. However, recently a different mechanism, namely purely electronic ferroelectricity, where charge order breaks inversion symmetry, has attracted considerable interest. Here we provide evidence for this exotic type of ferroelectricity, accompanied by antiferromagnetic spin order, in a two-dimensional organic charge-transfer salt, thus representing a new class of multiferroics. Quite unexpectedly for electronic ferroelectrics, dipolar and spin order arise nearly simultaneously. This can be ascribed to the loss of spin frustration induced by the ferroelectric ordering. Hence, here the spin order is driven by the ferroelectricity, in marked contrast to the spin-driven ferroelectricity in helical magnets.Comment: 8 pages, 9 figures (including 4 pages and 6 figures in supplementary information). Version 2 with minor errors corrected (legend of Fig. 3c and definition of vectors e and Q

Shunting operations at flat yards : retrieving freight railcars from storage tracks

In this paper, we study the railcar retrieval problem (RRT) where specified numbers of certain types of railcars have to be withdrawn from the storage tracks of a flat yard. This task arises in the daily operations of workshop yards for railcar maintenance. The objective is to minimize the total cost of shunting via methods such as minimizing the usage of shunting engines. We describe the RRT formally, present a mixed-integer program formulation, and prove the general case to be NP-hard. For some special cases, exact algorithms with polynomial runtimes are proposed. We also analyze several intuitive heuristic solution approaches motivated by observed real-world planning routines. We evaluate their average performances in simulations with different scenarios and provide their worst-case performance guarantee. We show that although the analyzed heuristics result in much better solutions than the naive planning approach, they are still on average 30%-50% from the optimal objective value and may result in up to 14 times higher costs in the worst case. Therefore, we conclude that optimization should be implemented in practice in order to save valuable resources. Furthermore, we analyze the impacts of yard layout and the widespread organizational routine of presorting on the railcar retrieval cost

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

A Formalism for the Systematic Treatment of Rapidity Logarithms in Quantum Field Theory

Many observables in QCD rely upon the resummation of perturbation theory to retain predictive power. Resummation follows after one factorizes the cross section into the rele- vant modes. The class of observables which are sensitive to soft recoil effects are particularly challenging to factorize and resum since they involve rapidity logarithms. In this paper we will present a formalism which allows one to factorize and resum the perturbative series for such observables in a systematic fashion through the notion of a "rapidity renormalization group". That is, a Collin-Soper like equation is realized as a renormalization group equation, but has a more universal applicability to observables beyond the traditional transverse momentum dependent parton distribution functions (TMDPDFs) and the Sudakov form factor. This formalism has the feature that it allows one to track the (non-standard) scheme dependence which is inherent in any scenario where one performs a resummation of rapidity divergences. We present a pedagogical introduction to the formalism by applying it to the well-known massive Sudakov form factor. The formalism is then used to study observables of current interest. A factorization theorem for the transverse momentum distribution of Higgs production is presented along with the result for the resummed cross section at NLL. Our formalism allows one to define gauge invariant TMDPDFs which are independent of both the hard scattering amplitude and the soft function, i.e. they are uni- versal. We present details of the factorization and resummation of the jet broadening cross section including a renormalization in pT space. We furthermore show how to regulate and renormalize exclusive processes which are plagued by endpoint singularities in such a way as to allow for a consistent resummation.Comment: Typos in Appendix C corrected, as well as a typo in eq. 5.6

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog