Effects of reservoir mechanical properties on induced seismicity during subsurface hydrogen storage.

The intermittent storage of hydrogen in subsurface porous media such as depleted gas fields could be pivotal to a successful energy transition. Numerical simulations investigate the intermittent storage of hydrogen in a porous, depleted subsurface reservoir. Various parametric studies are performed to assess the effect of mechanical properties of the reservoir (i.e. Young's modulus, Poisson's ratio, Biot coefficient and permeability) on the induced fault slip of a single through-going fault that transverses the entire reservoir. Simulations are run using a three-dimensional, finite element, fully coupled hydromechanical code with explicit representations of layers and faults. The effect of the domain mesh refinement and fault mesh refinement on the fault slip versus operation time solution is investigated. The fault is observed to slip in two distinct events, one during the second injection period and one in the third injection period. The fault is not observed to slip during the storage or withdrawal periods. It is found that in order to minimize seismic risk, a reservoir rock with high Young's modulus (>40 GPa), high Poisson's ratio (>0.30) and high Biot coefficient (>0.65) would be preferable for hydrogen storage. Reservoir rocks of low Young's modulus (10-30 GPa), intermediate Poisson's ratio (0.00-0.30) and low-to-intermediate Biot coefficient (0.25-0.65), at high injection rates, were found to have higher potential of inducing large seismic events.This article is part of the theme issue 'Induced seismicity in coupled subsurface systems'.

Intensification patterns and the probability of HbA1c goal attainment in Type 2 diabetes mellitus: real-world evidence for the concept of 'intensification inertia'.

AIMS: To assess the effects of 'clinical' and 'intensification inertia' by evaluating the impact of different intensification interventions on the probability of HbA1c goal attainment using real-world data. METHODS: Electronic health records (Cleveland Clinic, 2005-2016) were used to identify 7389 people with Type 2 diabetes mellitus and HbA1c ≥53 mmol/mol (≥7.0%), despite a stable regimen of two oral antihyperglycaemic drugs for ≥6 months. The participants were stratified by index HbA1c and analysed over a 6-month period for pharmacological intensification, and then for 12 additional months for HbA1c goal attainment (<53 mmol/mol). RESULTS: The probability of HbA1c goal attainment (Kaplan-Meier analysis) in the group with index HbA1c 53-63 mmol/mol (7.0-7.9%) was highest with the addition of oral antidiabetic drugs [57.3% (95% CI 52.1, 62.0)] or glucagon-like peptide-1 receptor agonists [56.7% (95% CI 40.4, 68.6)], in the 64-74 mmol/mol (8.0-8.9%) group with the addition of oral antidiabetic drugs [31.9% (95% CI 25.1, 38.1)] or insulin [30.6% (95% CI 18.3, 41.0)], and in the ≥75 mmol/mol (≥9.0%) group with the addition of glucagon-like peptide-1 receptor agonists [53.0% (95% CI 31.8, 67.6)] or insulin [43.5% (95% CI 36.4, 49.8)]. CONCLUSIONS: Numerical, but not statistically significant, differences in HbA1c goal attainment probability by type of intensification were most marked in people with the highest index HbA1c [≥75 mmol/mol (≥9.0%)]; in this group, injectable therapy showed trends toward greater glycaemic control benefits. Additional research into the phenomenon of intensification inertia is warranted.

Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood.

There are an estimated 2.1 million youth less than 15 years of age living with HIV globally (the majority perinatally HIV-infected [PHIV]) and millions more perinatally HIV-exposed uninfected (PHEU) youth who are expected to survive through adolescence and into adulthood. Transitioning from adolescence to young adulthood requires adaptation to more demanding social interactions, academic pressures, and individual responsibilities which place distinct demands on neurocognitive functions. This study examined longitudinal trajectories of neurocognitive test performance in the domains of processing speed (PS), working memory (WM), and executive functioning (EF) among PHIV and demographically similar PHEU from adolescence through young adulthood. Data for this paper come from four time points, spanning approximately 10 years, within the Child and Adolescent Self-Awareness and Health Study (CASAH). Youth age ranged from 15 to 29 years. Longitudinal linear mixed effect models were computed for each test. Few differences in performance were found on tests of EF and WM between PHIV and PHEU youth as they aged, though PHEU youth showed significantly better PS as they aged than PHIV youth. Future research is needed to understand these vulnerable youth's neurocognitive trajectories as a function of HIV infection and -exposure, biological functions and psychosocial stressors.

Psychological predictors of gestational outcomes in second trimester pregnant women: associations with daily uplifts.

PURPOSE: We investigated whether pregnancy/birth anxiety is associated with shorter gestation while maternal chronic stress and depressive symptoms are associated with lower birth weight; we also examined whether experiencing daily uplifts prenatally may contribute to a more favorable birth outcome. METHODS: Thirty-four healthy second trimester pregnant women responded to questions regarding their experience of pregnancy/birth anxiety, chronic stress, depressive symptoms, and daily uplifts. Information on birth outcome was obtained from medical records. RESULTS: Maternal pregnancy/birth anxiety, depression, and stress were unrelated to birth outcomes. Daily uplifts were associated with gestational age at birth (B = 2.0, p = 0.01), neonatal weight (B = 46.9, p = 0.00), and size (B = 10.6, p = 0.01). Our results suggest that pregnancy/birth anxiety is not associated with shorter gestation as well as depression and stress seem to not predict lower birth weight. CONCLUSION: We expand the literature by showing that experiencing daily uplifts during mid-gestation may further fetal development.

Preclinical validation of a targeted next generation sequencing-based comprehensive chromosome screening methodology in human blastocysts.

STUDY QUESTION: Can a novel targeted next generation sequencing (tNGS) platform accurately detect whole chromosome aneuploidy in a trophectoderm biopsy and provide additional information to improve testing? SUMMARY ANSWER: Karyotypes obtained by tNGS were concordant with other validated platforms and single nucleotide polymorphism genotyping information obtained can be used for improved detection and quality control. WHAT IS KNOWN ALREADY: qPCR-based whole chromosome aneuploidy screening is highly accurate in comparison to other common methods and has been shown to improve IVF success in two randomized clinical trials. With aneuploidy screening becoming standard of care in many IVF centres, there is a need to develop platforms with high throughput, low cost capabilities. STUDY DESIGN SIZE, DURATION: Twelve well-characterized cell lines were obtained from a commercial cell line repository and 31 discarded human blastocysts were obtained from 17 IVF patients who underwent comprehensive chromosome screening (CCS). PARTICIPANTS/MATERIAL, SETTING, METHODS: All samples were processed using a unique amplification strategy which directly incorporated sequencing library adapters and barcodes. Sequencing was performed on an Ion Torrent Proton. A custom bioinformatics pipeline was used to determine the karyotype for each sample. The consistency of tNGS diagnoses with either conventional karyotyping of cell lines or quantitative real-time PCR based CCS of blastocyst biopsies was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Overall consistency per sample of tNGS based CCS in 5-cell samples from a variety of cell lines was 99.2%. In the blinded analysis of rebiopsies of aneuploid blastocysts, an overall targeted tNGS CCS consistency of 98.7% was observed per sample. These data demonstrate the ability of tNGS based CCS to provide an accurate and high throughput evaluation of aneuploidy in the human blastocyst. LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: This study is limited to whole chromosome aneuploidy, as mosaicism and segmental aneuploidy have not been investigated. WIDER IMPLICATIONS OF THE FINDINGS: These data show an accurate, high throughput method, and with the greater depth of each amplicon sequenced in comparison to commercial kits, there is greater application available for single nucleotide polymorphism based analysis for quality control. STUDY FUNDING/COMPETING INTERESTS: This study was funded through intramural research funds provided by the Foundation for Embryonic Competence. There are no competing interests.

Longitudinal evaluation of diffusion tensor imaging and cognition in systemic lupus erythematosus.

Objective This pilot study aimed to examine longitudinal changes in brain structure and function in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging (DTI) and neuropsychological testing. Methods Fifteen female SLE patients with no history of major neuropsychiatric (NP) manifestations had brain magnetic resonance imaging (MRI) with DTI at baseline and approximately 1.5 years later. At the same time points, a standardized battery of cognitive tests yielding a global cognitive impairment index (CII) was administered. At baseline, the SLE patients had mean age of 34.0 years (SD = 11.4), mean education of 14.9 years (SD = 2.1), and mean disease duration of 121.5 months (SD = 106.5). The MRI images were acquired with a 3T GE MRI scanner. A DTI sequence with 33 diffusion directions and b-value of 800 s/mm2 was used. Image acquisition time was about 10 minutes. Results No significant change in cognitive dysfunction (from the CII) was detected. Clinically evaluated MRI scans remained essentially unchanged, with 62% considered normal at both times, and the remainder showing white matter (WM) hyperintensities that remained stable or resolved. DTI showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in bilateral cerebral WM and gray matter (GM) with no major change in NP status, medical symptoms, or medications over time. Lower FA was found in the following regions: left and right cerebral WM, and in GM areas including the parahippocampal gyrus, thalamus, precentral gyrus, postcentral gyrus, angular gyrus, parietal lobe, and cerebellum. Greater MD was found in the following regions: left and right cerebral WM, frontal cortex, left cerebral cortex, and the putamen. Conclusions This is the first longitudinal study of DTI and cognition in SLE, and results disclosed changes in both WM and GM without cognitive decline over an 18-month period. DTI abnormalities in our participants were not associated with emergent NP activity, medical decline, or medication changes, and the microstructural changes developed in the absence of macrostructural abnormalities on standard MRI. Microstructural changes may relate to ongoing inflammation, and the stability of cognitive function may be explained by medical treatment, the variability of NP progression in SLE, or the impact of cognitive reserve.

[What measures of perineal protection at birth are consensual in France? Results of a Delphi survey]. / Quelles mesures de protection périnéale à l'accouchement sont consensuelles en France ? Résultats d'une enquête Delphi.

OBJECTIVE: To evaluate expert's opinion in order to obtain a consensus on the different measures of perineal protection at the time of vaginal delivery. METHODS: A survey using the Delphi method was carried out with a panel of French obstetricians, urogynecologists and midwives. The questionnaire included 22 questions grouped into four groups: expulsive efforts, indications of episiotomy, episiotomy repair and other forms of perineal protection. The experts had to answer on a 9-point scale, both on the validity and the clarity of each proposal. After analysis of the replies of the first round, a second round was sent to the same experts for certain proposals. Each turn was the subject of two raises. To be validated, each proposal had to obtain a median equal to or greater than 7/9 and an agreement between the experts greater than 65% in the first round, and more than 75% in the second round. RESULTS: The study was conducted between March and October 2016. Of the 300 experts initially selected, 93 (31%) responded to the first round, including 63 obstetricians (67.7%), 12 urogynecologists (12.9%) and 18 midwives (19.4%). In the second round, 72 experts replied, representing 77.4% of the experts who also answered the first round. At the end of the two rounds, 11 proposals were validated, and 11 rejected. The following recommendations have been validated. Uterine expression should be proscribed. The two modes of pushing (blocked in Valsalva and by blowing) can be indifferently proposed, in case of fetal progression and in the absence of fetal distress. The midline episiotomy should be proscribed. The medio-lateral (or lateral) episiotomy should be left to the discretion of the accoucheur. The maintenance of the fetal head with one hand must be systematic to the expulsion to protect the perineum. Repair of the episiotomy should be made (except in some cases) with a rapid absorbable suture. The prescription of NSAIDs and/or painkillers of level 2 should be preferred to reduce the pain of post-natal perineal scars. CONCLUSION: Several measures of perineal protection at the time of vaginal delivery are consensual in France. Other measures should be studied further. LEVEL OF EVIDENCE: 4.

Gender-specific effects of oral hypoglycaemic agents on cancer risk in type 2 diabetes mellitus.

AIMS: To analyse the association between cancer incidence and oral diabetes therapy (biguanide, sulphonylurea, thiazolidinedione and meglitinide) in men and women with type 2 diabetes mellitus. METHODS: A retrospective analysis of the electronic health record-based Cleveland Clinic Diabetes Registry (25 613 patients) was cross-indexed with the histology-based tumour registry (48 051 cancer occurrences) over an 8-year period (1998-2006). Multiple imputations were used to account for missing data. Cox regression with propensity scores was used to model time for the development of incident cancer in each of the imputed datasets and the results were pooled. RESULTS: During 51 994 person follow-up years, 892 incident cancer cases were identified; prostate (14.5%) and breast (11.7%) malignancies were most frequent. In women, thiazolidinedione use was associated with a 32% decreased cancer risk compared with sulphonylurea use [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.48-0.97, in the adjusted analysis]. Comparison of insulin secretagogues (sulphonylurea and meglitinide) versus insulin sensitizers (biguanide and thiazolidinedione) demonstrated a 21% decreased cancer risk in insulin sensitizers [HR 0.79 (95% CI 0.64-0.98) in the adjusted analysis]. Oral diabetes therapy showed no significant difference in men. Adjustments were made for age, body mass index (BMI), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, coronary heart disease (CHD), diabetes oral monotherapy, race, gender, haemoglobin A1c, statin use, income, insulin use, glomerular filtration rate (GFR), new diabetes status, prior cancer, prior cerebrovascular accident (stroke or transient ischaemic event), systolic/diastolic blood pressure, tobacco use (ever/never) and the propensity score for receiving a biguanide. CONCLUSIONS: Oral insulin sensitizers, particularly thiazolidinedione, are associated with decreased malignancy risk in women with type 2 diabetes mellitus.

Preoperative blood glucose concentrations and postoperative outcomes after elective non-cardiac surgery: an observational study.

BACKGROUND: The association between preoperative blood glucose (BG) concentration and outcomes after non-cardiac surgery and the impact of the diabetes diagnosis status remain unclear. We tested two hypotheses: that preoperative BG is related to surgical outcomes; and that this relationship depends on the diabetes diagnosis status of the patient. METHODS: We retrospectively analysed data on 61 536 consecutive elective non-cardiac surgery patients treated at our tertiary care facility. Logistic regression models were used to test the hypotheses before and after adjustment for baseline patient characteristics. Our primary outcome was a composite of in-hospital serious complications and mortality. A second primary outcome was 1 yr mortality. RESULTS: The crude incidence of the composite in-hospital outcome was significantly related to preoperative BG (P<0.001), but not after covariable adjustment (P=0.40). This relationship did not significantly differ between patients with and without diagnosed diabetes (P=0.09). One year mortality was significantly related to preoperative BG, both univariably (P<0.001) and after covariable-adjustment (P<0.001). Patients with diagnosed diabetes and preoperative euglycaemia generally had worse 1 yr mortality than those without diabetes at the same BG {e.g. odds ratio (OR) [95% confidence interval (CI)] of 1.27 (1.06, 1.53) at 6 mmol litre(-1) (108 mg dl(-1)), P=0.003}. Conversely, hyperglycaemic patients with diagnosed diabetes displayed a significantly lower 1 yr mortality than hyperglycaemic patients without diabetes [OR (95% CI) of 0.58 (0.44, 0.77) at 12 mmol litre(-1) (216 mg dl(-1)), P<0.001]. CONCLUSIONS: For elective non-cardiac surgery, preoperative hyperglycaemia should be given greater consideration in patients without diabetes than in those with diagnosed diabetes.

The risk of overall mortality in patients with Type 2 diabetes receiving different combinations of sulfonylureas and metformin: a retrospective analysis.

AIMS: Sulfonylureas have been shown to increase mortality when used in combination with metformin. This may not be a class effect of sulfonylureas, but rather secondary to differences in properties inherent to the individual sulfonylureas (hypoglycaemic risk, sulfonylurea receptor selectivity and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the risk of overall mortality in patients with Type 2 diabetes treated with different combinations of sulfonylureas and metformin. METHODS: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record system to identify 7320 patients with Type 2 diabetes (3768 initiators of glyburide (glibenclamide) and metformin, 2277 initiators of glipizide and metformin and 1275 initiators of glimepiride and metformin), ≥ 18 years of age and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the electronic health record and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. RESULTS: No statistically significant difference in overall mortality risk was observed among the different combinations of sulfonylureas and metformin: glimepiride and metformin vs. glipizide and metformin (HR 1.03; 95% CI 0.89-1.20), glimepiride and metformin vs. glyburide (glibenclamide) and metformin (HR 1.08; 95% CI 0.90-1.30), or with glipizide and metformin vs. glyburide (glibenclamide) and metformin (HR 1.05; 95% CI 0.95-1.15). CONCLUSIONS: Our results did not identify an increased mortality risk among the different combinations of sulfonylureas and metformin, suggesting that overall mortality is not substantially influenced by the choice of sulfonylurea.

Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysis.

AIMS: It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes. METHODS: A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥ 18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. RESULTS: An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39-1.94), glyburide (HR 1.59; 95% CI 1.35-1.88), and glimepiride (HR 1.68; 95% CI 1.37-2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) versus metformin. CONCLUSIONS: Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD.

Associations among depression, demographic variables, and language impairments in chronic post-stroke aphasia.

INTRODUCTION: Depression may influence treatment participation and outcomes of people with post-stroke aphasia, yet its prevalence and associated characteristics in aphasia are poorly understood. Using retrospective data from an overarching experimental study, we examined depressive symptoms and their relationship to demographic and language characteristics in people with chronic aphasia. As a secondary objective, we compared prevalence of depressive symptoms among the overarching study's included and excluded participants. METHODS: We examined retrospective data from 121 individuals with chronic aphasia including depression scale scores, demographic information (sex, age, time post onset of stroke, education, race/ethnicity, and Veteran status), and scores on assessments of general and modality-specific language impairments. RESULTS: Approximately 50% of participants reported symptoms indicative of depressive disorders: 23% indicative of major depression and 27% indicative of mild depression. Sex (males) and comparatively younger age emerged as statistically significant variables associated with depressive symptoms; naming ability was minimally associated with depressive symptoms. Time post onset of stroke, education level, race/ethnicity, Veteran status, and aphasia severity were not significantly associated with depressive symptoms. Depression-scale scores were significantly higher for individuals excluded from the overarching study compared to those who were included. CONCLUSIONS: The rate of depressive disorders in this sample was higher than rates of depression reported in the general stroke literature. Participant sex, age, and naming ability emerged as factors associated with depressive symptoms, though these links appear complex, especially given variable reports from prior research. Importantly, depressive symptoms do not appear to diminish over time for individuals with chronic aphasia. Given these results and the relatively limited documentation of depression in aphasia literature, depression remains a pressing concern for aphasia research and routine clinical care.

Toward indicators of the performance of US Infrastructures under climate change risks.

Built infrastructures are increasingly disrupted by climate-related extreme events. Being able to monitor what climate change implies for US infrastructures is of considerable importance to all levels of decision-makers. A capacity to develop cross-cutting, widely applicable indicators for more than a dozen different kinds of infrastructure, however, is severely limited at present. The development of such indicators must be considered an ongoing activity that will require expansion and refinement. A number of recent consensus reports suggest four priorities for indicators that portray the impacts of climate change, climate-related extreme events, and other driving forces on infrastructure. These are changes in the reliability of infrastructure services and the implications for costs; changes in the resilience of infrastructures to climate and other stresses; impacts due to the interdependencies of infrastructures; and ongoing adaptation in infrastructures.

Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies.

BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%-100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor). RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%-100%) for normalized (r = 0.63, P < .001) and standardized (r = 0.66, P < .001) values. With binary cutoffs (ie, ≥50%; ≥80% tumor), predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Median relative CBV achieved the highest area under the curve (normalized = 0.87, standardized = 0.86) for predicting ≥50% tumor, while fractional tumor burden achieved the highest area under the curve (normalized = 0.77, standardized = 0.80) for predicting ≥80% tumor. CONCLUSIONS: Standardization of relative CBV achieves similar performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.

Chemical pruning of plants.

The lower alkyl esters of the C(8) to C(12) fatty acids and the C(8) to C(10) fatty alcohols selectively kill or inhibit the terminal meristem without damaging the axillary meristems, foliage, or stem tissue of a wide variety of plants. The axillary meristems develop at nearly the same time as those of plants whose terminal meristems have been removed manually. The concentration of the fatty acid esters and alcohols required to kill the terminal meristem range from 0.025 to 0.05M for herbaceous plants, 0.05 to 0.16M for semi-woody plants, and 0.16 to 0.27M for woody plants.

Seasonal abundance of anopheline mosquitoes and their association with rainfall and malaria along the Matapí River, Amapá, [corrected] Brazil.

Three communities separated by 1.5-7.0 km, along the Matapí River, Amapá State, Brazil, were sampled monthly from April 2003 to November 2005 to determine relationships between seasonal abundance of host-seeking anophelines, rainfall and malaria cases. Out of the 759 821 adult female anophelines collected, Anopheles darlingi Root (Diptera: Culicidae) was the most abundant (56.2%) followed by An. marajoara Galvão & Damasceno (24.6%), An. nuneztovari Gabaldón (12.4%), An. intermedius (Chagas) (4.4%) and An. triannulatus (Neiva and Pinto) (2.3%). Vector abundance, as measured by human landing catches, fluctuated during the course of the study and varied in species-specific ways with seasonal patterns of rainfall. Anopheles darlingi and An. triannulatus were more abundant during the wet-dry transition period in June to August, whereas An. marajoara began to increase in abundance in February in two villages, and during the wet-dry transition in the other village. Anopheles nuneztovari and An. intermedius increased in abundance shortly after the rains began in January to February. A generalized linear mixed model (GLMM) analysis of 32 consecutive months of collections showed significant differences in abundance for each species by village and date (P < 0.0001). Correlations between lagged rainfall and abundances also differed among species. A strong positive correlation of An. darlingi abundance with rainfall lagged by 4 and 5 months (Pearson's r = 0.472-0.676) was consistent among villages and suggests that rainfall may predict vector abundance. Significant correlations were detected between numbers of malaria cases and abundances of suspected vector species. The present study shows how long-term field research may connect entomological and climatological correlates with malaria incidence.

Accurate Patient-Specific Machine Learning Models of Glioblastoma Invasion Using Transfer Learning.

BACKGROUND AND PURPOSE: MR imaging-based modeling of tumor cell density can substantially improve targeted treatment of glioblastoma. Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a transfer learning method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient's own histologic data. MATERIALS AND METHODS: We recruited patients with primary glioblastoma undergoing image-guided biopsies and preoperative imaging, including contrast-enhanced MR imaging, dynamic susceptibility contrast MR imaging, and diffusion tensor imaging. We calculated relative cerebral blood volume from DSC-MR imaging and mean diffusivity and fractional anisotropy from DTI. Following image coregistration, we assessed tumor cell density for each biopsy and identified corresponding localized MR imaging measurements. We then explored a range of univariate and multivariate predictive models of tumor cell density based on MR imaging measurements in a generalized one-model-fits-all approach. We then implemented both univariate and multivariate individualized transfer learning predictive models, which harness the available population-level data but allow individual variability in their predictions. Finally, we compared Pearson correlation coefficients and mean absolute error between the individualized transfer learning and generalized one-model-fits-all models. RESULTS: Tumor cell density significantly correlated with relative CBV (r = 0.33, P < .001), and T1-weighted postcontrast (r = 0.36, P < .001) on univariate analysis after correcting for multiple comparisons. With single-variable modeling (using relative CBV), transfer learning increased predictive performance (r = 0.53, mean absolute error = 15.19%) compared with one-model-fits-all (r = 0.27, mean absolute error = 17.79%). With multivariate modeling, transfer learning further improved performance (r = 0.88, mean absolute error = 5.66%) compared with one-model-fits-all (r = 0.39, mean absolute error = 16.55%). CONCLUSIONS: Transfer learning significantly improves predictive modeling performance for quantifying tumor cell density in glioblastoma.

Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema.

The current concepts of the pathogenesis of emphysema hold that progressive, chronic destruction of the alveolar structures occurs because there was in imbalance between the proteases and antiproteases in the lower respiratory tract. In this context, proteases, particularly neutrophil elastase, work unimpeded to destroy the alveolar structures. This concept has evolved from consideration of patients with alpha 1-antitrypsin deficiency, who have decreased levels of serum alpha 1-antitrypsin and who have progressive panacinar emphysema. To directly assess the antiprotease side of this equation, the lower respiratory tract of non-smoking individuals with normal serum antiproteases and individuals with PiZ homozygous alpha 1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract. These studies demonstrated that: (a) alpha 1-antitrypsin is the major antielastase of the normal human lower respiratory tract; (b) alpha 2-macroglobulin, a large serum antielastase, and the bronchial mucous inhibitor, an antielastase of the central airways, do not contribute to the antielastase protection of the human alveolar structures; (c) individuals with PiZ alpha 1-antitrypsin deficiency have little or no alpha 1-antitrypsin in their lower respiratory tract and have no alternative antiprotease protection against neutrophil elastase; and (d) the lack of antiprotease protection of the lower respiratory tract of PiZ individuals is a chronic process, suggesting their vulnerability to neutrophil elastase is always present.

Effect of training and experience on qualitative and quantitative CT perfusion data.

BACKGROUND AND PURPOSE: To evaluate interobserver reliability of obtaining CT perfusion (CTP) data for qualitative identification of perfusion abnormality and quantitative assessment through regions-of-interest (ROIs) placement. MATERIALS AND METHODS: Six observers participated in the study (neuroradiology attending physician, neurology attending physician, neuroradiology fellow, radiology resident physician, senior and junior CT technologists). After a brief training session, each observer evaluated 20 CTP datasets for qualitative identification of a right- or left-sided perfusion abnormality or symmetric perfusion. Observers also placed a single ROI of standard size to obtain quantitative data on the most severely hypoperfused region. An additional 10 ROIs were placed on the cortex to quantitatively evaluate global cortical perfusion. Mean quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values were analyzed. RESULTS: The kappa values for qualitative assessment of a perfusion abnormality ranged from 0.55 to 1.0. Coefficients of variation for quantitative assessment of ischemia/infarct region were 27.10% for CBF, 13.33% for CBV, and 4.66% for MTT. Coefficients of variation for quantitative assessment of global cortical perfusion were 11.88% for CBF, 13.66% for CBV, and 3.55% for MTT. The junior CT technologist and neuroradiology fellow showed significant differences compared with other observers for the ischemia/infarct region and global cortical perfusion, respectively. CONCLUSION: Overall, quantitative differences seen in this study would not necessarily affect quality of interpretation of ischemia/infarct region or global cortical perfusion. Therefore, obtaining qualitative and quantitative CTP data can reliably be performed in the clinical setting among observers with various levels of skill and experience when using a uniform and standard technique.

Defining optic nerve tortuosity.

BACKGROUND AND PURPOSE: Optic nerve tortuosity is one of several nonmalignant abnormalities documented on MR imaging in patients with neurofibromatosis type 1 and may be related to the development of optic pathway gliomas. This study seeks an operational definition for optic nerve tortuosity. MATERIALS AND METHODS: A focus group of 3 pediatric neuroradiologists reviewed 20 MR images of the brain and orbits of patients suspected to have optic nerve tortuosity in the absence of optic pathway glioma and found 6 radiographic factors that occurred frequently. Subsequently, 28 MR images were assessed for the presence of optic nerve tortuosity, using a global assessment question that reflects a neuroradiologist's confidence in the presence of optic nerve tortuosity, and for the presence of the 6 radiographic factors, to identify a combination of these factors that best predicted a diagnosis of optic nerve tortuosity. RESULTS: We found perfect inter-rater agreement between 3 readers on the presence/absence of tortuosity in 75% of cases. Lack of congruity of the optic nerves, in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves, when found together are sensitive (89%) and specific (93%) for a diagnosis of tortuosity on the global scale. The absence of these 2 factors, along with absence of deviation of the optic nerve within the axial plane, provides a reliable test to exclude tortuosity. CONCLUSION: Lack of congruity of the optic nerves in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves together provide an operational radiographic definition of optic nerve tortuosity.