Infection is an important, preventable cause of maternal morbidity, and pregnancy-related sepsis accounts for 11% of maternal deaths. However, frequency of maternal infection is poorly described, ...and, to our knowledge, it remains the one major cause of maternal mortality without a systematic review of incidence. Our objective was to estimate the average global incidence of maternal peripartum infection.
We searched Medline, EMBASE, Global Health, and five other databases from January 2005 to June 2016 (PROSPERO: CRD42017074591). Specific outcomes comprised chorioamnionitis in labour, puerperal endometritis, wound infection following cesarean section or perineal trauma, and sepsis occurring from onset of labour until 42 days postpartum. We assessed studies irrespective of language or study design. We excluded conference abstracts, studies of high-risk women, and data collected before 1990. Three reviewers independently selected studies, extracted data, and appraised quality. Quality criteria for incidence/prevalence studies were adapted from the Joanna Briggs Institute. We used random-effects models to obtain weighted pooled estimates of incidence risk for each outcome and metaregression to identify study-level characteristics affecting incidence. From 31,528 potentially relevant articles, we included 111 studies of infection in women in labour or postpartum from 46 countries. Four studies were randomised controlled trials, two were before-after intervention studies, and the remainder were observational cohort or cross-sectional studies. The pooled incidence in high-quality studies was 3.9% (95% Confidence Interval CI 1.8%-6.8%) for chorioamnionitis, 1.6% (95% CI 0.9%-2.5%) for endometritis, 1.2% (95% CI 1.0%-1.5%) for wound infection, 0.05% (95% CI 0.03%-0.07%) for sepsis, and 1.1% (95% CI 0.3%-2.4%) for maternal peripartum infection. 19% of studies met all quality criteria. There were few data from developing countries and marked heterogeneity in study designs and infection definitions, limiting the interpretation of these estimates as measures of global infection incidence. A limitation of this review is the inclusion of studies that were facility-based or restricted to low-risk groups of women.
In this study, we observed pooled infection estimates of almost 4% in labour and between 1%-2% of each infection outcome postpartum. This indicates maternal peripartum infection is an important complication of childbirth and that preventive efforts should be increased in light of antimicrobial resistance. Incidence risk appears lower than modelled global estimates, although differences in definitions limit comparability. Better-quality research, using standard definitions, is required to improve comparability between study settings and to demonstrate the influence of risk factors and protective interventions.
A linear analysis is applied to a multi-thousand member “perturbed physics" GCM ensemble to identify the dominant physical processes responsible for variation in climate sensitivity across the ...ensemble. Model simulations are provided by the distributed computing project, climate prediction.net . A principal component analysis of model radiative response reveals two dominant independent feedback processes, each largely controlled by a single parameter change. The leading EOF was well correlated with the value of the entrainment coefficient--a parameter in the model's atmospheric convection scheme. Reducing this parameter increases high vertical level moisture causing an enhanced clear sky greenhouse effect both in the control simulation and in the response to greenhouse gas forcing. This effect is compensated by an increase in reflected solar radiation from low level cloud upon warming. A set of 'secondary' cloud formation parameters partly modulate the degree of shortwave compensation from low cloud formation. The second EOF was correlated with the scaling of ice fall speed in clouds which affects the extent of cloud cover in the control simulation. The most prominent feature in the EOF was an increase in longwave cloud forcing. The two leading EOFs account for 70% of the ensemble variance in λ--the global feedback parameter. Linear predictors of feedback strength from model climatology are applied to observational datasets to estimate real world values of the overall climate feedback parameter. The predictors are found using correlations across the ensemble. Differences between predictions are largely due to the differences in observational estimates for top of atmosphere shortwave fluxes. Our validation does not rule out all the strong tropical convective feedbacks leading to a large climate sensitivity.
Functional characterization of bacterial proteins lags far behind the identification of new protein families. This is especially true for bacterial species that are more difficult to grow and ...genetically manipulate than model systems such as
and
To facilitate functional characterization of mycobacterial proteins, we have established a Mycobacterial Systems Resource (MSR) using the model organism
This resource focuses specifically on 1,153 highly conserved core genes that are common to many mycobacterial species, including
, in order to provide the most relevant information and resources for the mycobacterial research community. The MSR includes both biological and bioinformatic resources. The biological resource includes (i) an expression plasmid library of 1,116 genes fused to a fluorescent protein for determining protein localization; (ii) a library of 569 precise deletions of nonessential genes; and (iii) a set of 843 CRISPR-interference (CRISPRi) plasmids specifically targeted to silence expression of essential core genes and genes for which a precise deletion was not obtained. The bioinformatic resource includes information about individual genes and a detailed assessment of protein localization. We anticipate that integration of these initial functional analyses and the availability of the biological resource will facilitate studies of these core proteins in many
species, including the less experimentally tractable pathogens
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Diseases caused by mycobacterial species result in millions of deaths per year globally, and present a substantial health and economic burden, especially in immunocompromised patients. Difficulties inherent in working with mycobacterial pathogens have hampered the development and application of high-throughput genetics that can inform genome annotations and subsequent functional assays. To facilitate mycobacterial research, we have created a biological and bioinformatic resource (https://msrdb.org/) using
as a model organism. The resource focuses specifically on 1,153 proteins that are highly conserved across the mycobacterial genus and, therefore, likely perform conserved mycobacterial core functions. Thus, functional insights from the MSR will apply to all mycobacterial species. We believe that the availability of this mycobacterial systems resource will accelerate research throughout the mycobacterial research community.
In this prospective phase 2 clinical trial conducted by Cancer and Leukemia Group B (CALGB, now the Alliance), we studied decitabine as maintenance therapy for younger adults with acute myeloid ...leukemia (AML) who remained in first complete remission (CR1) following intensive induction and consolidation. Given that decitabine is clinically active in AML and with hypomethylating activity distinct from cytotoxic chemotherapy, we hypothesized that 1 year of maintenance therapy would improve disease-free survival (DFS) for AML patients <60 years, who did not receive allogeneic stem cell transplantation in CR1. After blood count recovery from final consolidation, patients received decitabine at 20 mg/m
intravenously daily for 4-5 days, every 6 weeks for eight cycles. One hundred and thirty-four patients received decitabine and 85 (63%) had favorable risk AML. The median number of cycles received was 7 (range: 1-8) and the primary reason for discontinuation was relapse. DFS at 1 year and 3 years was 79% and 54%, respectively. These results are similar to the outcomes in the historical control comprising similar patients treated on recent CALGB trials. Thus, maintenance with decitabine provided no benefit overall. Standard use of decitabine maintenance in younger AML patients in CR1 is not warranted. This trial was registered at www.clinicaltrials.gov as NCT00416598.
Peripheral neuropathy is a major toxicity of vincristine, yet no strategies exist for identifying adult patients at high‐risk. We used a case–control design of 48 adults receiving protocol therapy ...for acute lymphoblastic leukemia (ALL) who developed vincristine‐induced neuropathy (NCI grade 2–4) during treatment, and 48 matched controls who did not develop grade 2–4 neuropathy. Peripheral neuropathy was prospectively graded by National Cancer Institute (NCI) criteria. CEP72 promoter genotype (rs924607) was determined using polymerase chain reaction (PCR)‐based single nucleotide polymorphism (SNP) genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31% vs. 10%, P = 0.0221) and the incidence of vincristine‐induced neuropathy (grades 2–4) was significantly higher in patients homozygous for the CEP72 T/T genotype. 75% of the 20 patients homozygous for the CEP72 T allele developed grade 2–4 neuropathy, compared to 44% of patients with CEP72 CC or CT genotype (P = 0.0221). The CEP72 polymorphism can identify adults at increased risk of vincristine‐induced peripheral neuropathy.
Cognitive deficits constitute core features of schizophrenia, but the trajectories of cognitive difficulties in chronic untreated schizophrenia remain unclear.
To assess the association of ...neuropsychological deficits with duration of untreated psychosis in individuals with chronic untreated schizophrenia.
Community-dwelling individuals with chronic untreated schizophrenia (untreated patient group) and individuals without mental illness (control group) were recruited from predominantly rural communities in Ningxia, China between June 20, 2016, and August 6, 2019, and administered the Structured Clinical Interview for DSM-IV, the Mini-Mental State Examination, an 8-test version of the MATRICS Consensus Cognition Battery adapted for use in individuals with low levels of education, and a measure of social cognition.
Comparison of cognitive test scores between the two groups and association of cognitive test scores with duration of untreated schizophrenia.
The patient group included 197 individuals with chronic untreated schizophrenia (101 men 51.3%; mean SD age, 52.1 11.8 years; median interquartile range years of schooling, 3 0-6 years; median interquartile range years of untreated psychosis, 22.9 14.9-32.8 years). The control group included 220 individuals (118 men 53.6%; mean SD age, 52.1 11.2 years; median interquartile range years of schooling, 4 0-6 years). The untreated patient group performed significantly worse than the control group on all cognitive measures (adjusted partial Spearman correlation coefficient Spearman ρ ranged from -0.35 for the revised Chinese version of the Reading the Mind in the Eyes Test to -0.60 for the Brief Visuospatial Memory Test-Revised; P < .001 for all comparisons). Longer durations of untreated psychosis were associated with lower performance in 3 MATRICS Consensus Cognition Battery measures assessing different aspects of executive functioning (Brief Visuospatial Memory Test-Revised ρ = -0.20; P = .04; Brief Assessment of Cognition in Schizophrenia, Symbol Coding subtest ρ = -0.35; P < .001; and Neuropsychological Assessment Battery, Mazes subtest ρ = -0.24; P = .01). The median duration of untreated psychosis (22.9 years) was associated with estimated score reductions in the 3 measures of 34% (95% CI, 10%-52%), 43% (95% CI, 28%-55%), and 57% (95% CI, 31%-73%), respectively.
The findings of this study suggest that long-term untreated schizophrenia was associated with decreases in selective cognitive abilities; both neurodegenerative pathology and neurodevelopmental dysfunction may be factors in cognition in persistent psychosis. Expanding research to include cohorts of patients from underserved rural communities in low- and middle-income countries may provide new insights about the etiological factors, disease course, and management of schizophrenia.
Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls ...below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group.
On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the ...feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18-50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56-78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56-76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph-) was 71% (95% CI 58-81%), and for all 74 Ph- patients the 4-year OS was 70% (95% CI 58-79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.
Asian soybean rust (ASR), caused by Phakopsora pachyrhizi and recently discovered for the first time in continental United States, has been of concern to the U.S. agricultural industry for more than ...30 years. Since little soybean rust resistance is known, and resistance is often difficult to detect or quantitate, we initiated a project to develop a better, more quantitative, method. The methodology determined the average numbers and diameters of uredinia in lesions that developed on leaves of inoculated plants 14 days after inoculation. It was used to compare virulence of P. pachyrhizi isolates from Asia and Australia and P. meibomiae from Puerto Rico and Brazil, collected as many as 30 years earlier, with isolates of P. pachyrhizi recently collected from Africa or South America. Susceptible reactions to P. pachyrhizi resulted in tan-colored lesions containing 1 to 14 uredinia varying greatly in size within individual lesions. In contrast, on these same genotypes at the same time of year, resistance to other P. pachyrhizi isolates was typified by 0 to 6 small uredinia in reddish-brown to dark-brown lesions. Using appropriate rust resistant and rust susceptible genotypes as standards, examination of uredinia 14 days after inoculation allowed quantitative comparisons of sporulation capacities, one measure of susceptibility or resistance to soybean rust. The study verified the presence and ability to detect all known major genes for resistance to soybean rust in the original sources of resistance. It demonstrated that soybean lines derived from the original PI sources, and presumed to possess the resistance genes, in actuality may lack the gene or express an intermediate reaction to the rust pathogen. We suggest that a determination of numbers and sizes of uredinia will detect both major gene and partial resistance to soybean rust.
Extremely arid conditions in tropical Africa occurred in several discrete episodes between 135 and 90 ka, as demonstrated by lake core and seismic records from multiple basins Scholz CA, Johnson TC, ...Cohen AS, King JW, Peck J, Overpeck JT, Talbot MR, Brown ET, Kalindekafe L, Amoako PYO, et al. (2007) Proc Natl Acad Sci USA 104:16416-16421. This resulted in extraordinarily low lake levels, even in Africa's deepest lakes. On the basis of well dated paleoecological records from Lake Malawi, which reflect both local and regional conditions, we show that this aridity had severe consequences for terrestrial and aquatic ecosystems. During the most arid phase, there was extremely low pollen production and limited charred-particle deposition, indicating insufficient vegetation to maintain substantial fires, and the Lake Malawi watershed experienced cool, semidesert conditions (<400 mm/yr precipitation). Fossil and sedimentological data show that Lake Malawi itself, currently 706 m deep, was reduced to an almost equal to125 m deep saline, alkaline, well mixed lake. This episode of aridity was far more extreme than any experienced in the Afrotropics during the Last Glacial Maximum (almost equal to35-15 ka). Aridity diminished after 95 ka, lake levels rose erratically, and salinity/alkalinity declined, reaching near-modern conditions after 60 ka. This record of lake levels and changing limnological conditions provides a framework for interpreting the evolution of the Lake Malawi fish and invertebrate species flocks. Moreover, this record, coupled with other regional records of early Late Pleistocene aridity, places new constraints on models of Afrotropical biogeographic refugia and early modern human population expansion into and out of tropical Africa.
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