The influence of the use of improved sanitation facilities and improved drinking-water sources on the diarrhea-associated deaths in children under 5 years

Diarrhea is one of the main causes of children's death. Due to the importance of health in children under 5 years, this study has been conducted to determine the influence of the use of improved sanitation facilities (UISF) and the use of improved drinking-water sources (UIDWS) on the diarrhea-associated deaths per 1000 live births in this age group. An ecologic study was conducted in 75 countries, and the data on UIDWS and UISF information have been collected by World Health Organization (WHO) under a program named “Global Analysis and Assessment of Sanitation and Drinking-Water” (GLAAS). To determine the correlation between UIDWS and UISF with the diarrhea-associated deaths in children, Pearson correlation was applied. Besides, a linear regression analysis was used to investigate the relationship between UIDWS and UISF with the diarrhea-associated deaths in children. According to the findings, there was a significant statistical relationship between UIDWS and UISF with the diarrhea-associated deaths in children (p < 0.001). The diarrhea-associated deaths in children under 5 years are influenced by factors such as UIDWS and UISF, and this rate can be reduced making UISF and UIDWS available for people and especially people of rural areas.     

The course of diabetes in children,adolescents and young adults: does the autoimmunity status matter?

Background

Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes.The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0–25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies.

Methods

Cross-sectional population-based study was performed covering 100% of pediatric (n?=?860) and 70% of 18–25 years old adult patients (n?=?349) with type 1 diabetes in Lithuania.

Results

No antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p?<?0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p?<?0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p?>?0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p?<?0.05).

Conclusion

Antibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.

     

Cardiovascular causes of sudden unexpected death in children and adolescents (0–17 years)

Background

Little is known about the causes of unexpected death in minors (0–17 years). In young adults an important cause is cardiovascular disease, with primary arrhythmogenic disorders, atherosclerotic events, cardiomyopathies and myocarditis as main contributors. The aim of this autopsy study was to determine the contribution of cardiovascular disease to unexpected death in minors.

Methods and results

In the Netherlands, systematic investigation of all cases of unexplained death in minors was compulsory in a nationwide governmental project during a 15-month period. Autopsies were performed according to a standardised protocol (autopsy rate 85%). A cardiovascular cause of death was found in 13/56 cases (23%). In the group <1 year, the main cardiovascular causes were various congenital defects (n?=?3) and myocarditis (n?=?2). In the 1–9 year group, no cardiovascular causes were found. In the 10–14 year group, hypertrophic cardiomyopathy (n?=?1) and ruptured ascending aortic aneurysm (n?=?1) were among the observed cardiovascular causes. In 14/56 (25%) cases autopsy revealed no structural abnormalities that could explain the sudden death, mostly in the group <1 year.

Conclusion

This national cohort with a high autopsy rate reveals a high incidence (23%) of cardiovascular diseases as the pathological substrate of sudden unexpected death in children. Another high percentage of minors (25%) showed no structural abnormalities, with the possibility of a genetic arrhythmia. These findings underline the importance of systematic autopsy in sudden death in minors, with implications for cardiogenetic screening of relatives.

     

Oligogenic combinations associated with breast cancer risk in women under 53 years of age

Common, but weakly penetrant, functional polymorphisms probably account for most of the genetic risk for breast cancer in the general population. Current polygenic risk models assume that component genes act independently. To test for potential gene-gene interactions, single nucleotide polymorphisms in ten genes with known or predicted roles in breast carcinogenesis were examined in a case-control study of 631 Caucasian women diagnosed with breast cancer under the age of 53 years and 1,504 controls under the age of 53 years. Association of breast cancer risk with individual genes and with two- and three-gene combinations was analyzed. Sixty-nine oligogenotypes from 37 distinct two- and three-gene combinations met stringent criteria for significance. Significant odds ratios (ORs) covered a 12-fold range: 0.5-5.9. Of the observed ORs, 17% differed significantly from the ORs predicted by a model of independent gene action, suggesting epistasis, i.e., that these genes interact to affect breast cancer risk in a manner not predictable from single gene effects. Exploration of the biological basis for these oligogenic interactions might reveal etiologic or therapeutic insights into breast cancer and other cancers.     

Exposure to lead and cadmium and associated factors in children 0–17 years of age living in an area contaminated by metals

This article analyzes some characteristics and conditions associated with Pb and Cd exposure using an exploratory approach, relating them to the levels of Pb and Cd in blood (blood lead levels [BLL] and blood cadmium levels [BCL]) in children 0–17 years of age living in an area contaminated by metals. BLL and BCL values were determined for each child and questionnaires were applied to their parents. Significant differences were found in mean BLL values according to race (p = .03), family history of intoxication by Pb (p = .004), if a family member was a metallurgy worker (p = .047), if a family member performed activities in the area of metallurgy (p = .03), and mother's employment status (p = .014). The following characteristics were associated with increased risk of BLL above 5.0 mg/dL in children: race, having a family record of intoxication by lead, and having a parent who worked at the plant. BLC values are not significantly associated with any of the studied characteristics. It may be concluded that BLL values are influenced by the social indicators of the population.     

Weather conditions and daily television use in the Netherlands, 1996–2005

This study examines the impact of daily atmospheric weather conditions on daily television use in the Netherlands for the period 1996–2005. The effects of the weather parameters are considered in the context of mood and mood management theory. It is proposed that inclement and uncomfortable weather conditions are associated with lower human mood, and that watching entertainment and avoiding informational programs may serve to repair such mood. We consequently hypothesize that people spend more time watching television if inclement and uncomfortable weather conditions (low temperatures, little sunshine, much precipitation, high wind velocity, less daylight) coincide with more airtime for entertainment programs, but that they view less if the same weather conditions coincide with more airtime devoted to information fare. We put this interaction thesis to a test using a time series analysis of daily television viewing data of the Dutch audience obtained from telemeters (T = 3,653), merged with meteorological weather station statistics and program broadcast figures, whilst controlling for a wide array of recurrent and one-time societal events. The results provide substantial support for the proposed interaction of program airtime and the weather parameters temperature and sunshine on aggregate television viewing time. Implications of the findings are discussed.     

The fate of 15NH4 + labeled deposition in a Scots pine forest in the Netherlands under high and lowered NH4 + deposition, 8 years after application

To study the long-term fate of deposited ammonium (NH₄ ⁺) in a Scots pine forest stand under high nitrogen (N) deposition in the Netherlands we re-sampled the plots of a ¹⁵N tracer experiment with high (i.e. ambient) and lowered N deposition in this stand 8 years after application of the tracer. The results were compared with results obtained 7 years earlier. In the 7 years between the samplings the ¹⁵N deltas of needles, twigs and upper organic soil layer had converged to similar values still above the natural ¹⁵N abundance, suggesting equilibration as a result of intensive cycling of N among these pools. Bark and wood had lower deltas than needles and twigs, but if the label found was attributed to tissue synthesized since the start of the labeling only, bark values were similar to needles and twigs, whereas wood values were higher indicating retranslocation of N into older wood. Mineral soil lost all ¹⁵N label it had accumulated after 1 year indicating that this label had not been strongly bound. The first year the low N treatment had retained more of the labeled NH₄ ⁺ deposition than the high N treatment, but in the seven subsequent years relatively more label was retained in the latter. This better retention after 7 years was ascribed to a larger fraction of label taken up by the vegetation in the high N treatment. This shows that the vegetation can affect the label dynamics despite the fact that only a relatively small amount of label was present in the aboveground vegetation.     

Is emotion recognition the only problem in ADHD? effects of pharmacotherapy on face and emotion recognition in children with ADHD

The objectives of this study were to evaluate both face and emotion recognition, to detect differences among attention deficit and hyperactivity disorder (ADHD) subgroups, to identify effects of the gender and to assess the effects of methylphenidate and atomoxetine treatment on both face and emotion recognition in patients with ADHD. The study sample consisted of 41 male, 29 female patients, 8–15 years of age, who were diagnosed as having combined type ADHD (N = 26), hyperactive/impulsive type ADHD (N = 21) or inattentive type ADHD (N = 23) but had not previously used any medication for ADHD and 35 male, 25 female healthy individuals. Long-acting methylphenidate (OROS-MPH) was prescribed to 38 patients, whereas atomoxetine was prescribed to 32 patients. The reading the mind in the eyes test (RMET) and Benton face recognition test (BFRT) were applied to all participants before and after treatment. The patients with ADHD had a significantly lower number of correct answers in child and adolescent RMET and in BFRT than the healthy controls. Among the ADHD subtypes, the hyperactive/impulsive subtype had a lower number of correct answers in the RMET than the inattentive subtypes, and the hyperactive/impulsive subtype had a lower number of correct answers in short and long form of BFRT than the combined and inattentive subtypes. Male and female patients with ADHD did not differ significantly with respect to the number of correct answers on the RMET and BFRT. The patients showed significant improvement in RMET and BFRT after treatment with OROS-MPH or atomoxetine. Patients with ADHD have difficulties in face recognition as well as emotion recognition. Both OROS-MPH and atomoxetine affect emotion recognition. However, further studies on the face and emotion recognition are needed in ADHD.     

Clinicopathological and immunohistochemical study of 29 cases of solid-pseudopapillary neoplasms of the pancreas in patients under 20 years of age along with detailed review of literature

Background

Multiplex immunohistochemistry (mIHC) permits the labeling of six or more distinct cell types within a single histologic tissue section. The classification of each cell type requires detection of uniquely colored chromogens localized to cells expressing biomarkers of interest. The most comprehensive and reproducible method to evaluate such slides is to employ digital pathology and image analysis pipelines to whole-slide images (WSIs). Our suite of deep learning tools quantitatively evaluates the expression of six biomarkers in mIHC WSIs. These methods address the current lack of readily available methods to evaluate more than four biomarkers and circumvent the need for specialized instrumentation to spectrally separate different colors. The use case application for our methods is a study that investigates tumor immune interactions in pancreatic ductal adenocarcinoma (PDAC) with a customized mIHC panel.

Methods

Six different colored chromogens were utilized to label T-cells (CD3, CD4, CD8), B-cells (CD20), macrophages (CD16), and tumor cells (K17) in formalin-fixed paraffin-embedded (FFPE) PDAC tissue sections. We leveraged pathologist annotations to develop complementary deep learning-based methods: (1) ColorAE is a deep autoencoder which segments stained objects based on color; (2) U-Net is a convolutional neural network (CNN) trained to segment cells based on color, texture and shape; and (3) ensemble methods that employ both ColorAE and U-Net, collectively referred to as ColorAE:U-Net. We assessed the performance of our methods using: structural similarity and DICE score to evaluate segmentation results of ColorAE against traditional color deconvolution; F1 score, sensitivity, positive predictive value, and DICE score to evaluate the predictions from ColorAE, U-Net, and ColorAE:U-Net ensemble methods against pathologist-generated ground truth. We then used prediction results for spatial analysis (nearest neighbor).

Results

We observed that (1) the performance of ColorAE is comparable to traditional color deconvolution for single-stain IHC images (note: traditional color deconvolution cannot be used for mIHC); (2) ColorAE and U-Net are complementary methods that detect six different classes of cells with comparable performance; (3) combinations of ColorAE and U-Net in ensemble methods outperform ColorAE and U-Net alone; and (4) ColorAE:U-Net ensemble methods can be employed for detailed analysis of the tumor microenvironment (TME).

Summary

We developed a suite of scalable deep learning methods to analyze 6 distinctly labeled cell populations in mIHC WSIs. We evaluated our methods and found that they reliably detected and classified cells in the PDAC tumor microenvironment. We also utilized the ColorAE:U-Net ensemble method to analyze 3 mIHC WSIs with nearest neighbor spatial analysis. We demonstrate a proof of concept that these methods can be employed to quantitatively describe the spatial distribution of immune cells within the tumor microenvironment. These complementary deep learning methods are readily deployable for use in clinical research studies.

     

Development of pertussis vaccine production and control in the National Institute of Public Health in the Netherlands during the years 1950–1962

The development of the pertussis vaccine production in the National Institute of Public Health in the Netherlands since 1953, and the results with the consecutive lots of vaccine in the mouse protection test and the U.S.A. toxicity test are described. The results in the latter test are compared with the results of a locally developed guinea pig toxicity test. Special attention is given to the difficulties encountered when the U.S.A. toxicity test is used for adsorbed DPT vaccines. The potency data of all lots of DPT vaccines produced since 1958 fall within the limits of the potency test as prescribed in the U.S.A. Minimum Requirements. There are indications that the increased potency of the vaccine may have led to a lower mortality rate of pertussis.     

Do increases in the availability of standing dead trees affect the abundance,nest-site use,and niche partitioning of great spotted and middle spotted woodpeckers in riverine forests?

Standing dead trees may be a limited resource for woodpeckers in managed forests, especially for species that rely on dead wood for their nest or roost cavity, and as foraging sites. Effective conservation strategies for woodpeckers require a detailed knowledge of species’ responses to dead wood availability. To investigate the importance of standing dead wood (snags) for the abundance and nest-site use of the great spotted woodpecker Dendrocopos major and middle spotted woodpecker Leiopicus medius in mature riverine forests, we compared the responses of birds between two periods—before mass mortality, and during a pulse in standing dead trees. The density of standing dead trees available for cavity excavation by the great spotted woodpecker and the middle spotted woodpecker increased significantly during the study period: 37-fold and 4-fold, respectively. Temporal trends in the abundance of both woodpecker species from 2000 to 2015 were not significant. Great spotted woodpeckers were significantly more likely to use dead trees and places with wounds in species other than oak and ash during the outbreak period than in the pre-outbreak period. Middle spotted woodpeckers were significantly less likely to excavate cavities in tree species other than oak and ash in the outbreak period, but dead trees were more likely selected. An interspecific comparison suggests that the probability of a nest-hole having been excavated by a middle spotted woodpecker increased with a nest-hole sited in ash, in a dead tree, in a limb/branch, and decreased with a nest-hole in a closed forest. These findings suggest that woodpecker species, especially weak excavators, may benefit from an increase in dead wood availability leading to nest niche shifts into more favorable substrates for cavity excavation. However, a strong increase in dead wood availability does not modify the general pattern of niche partitioning between great spotted and middle spotted woodpeckers. Conservation plans for the specialized middle spotted woodpecker must consider the preference for dead and decaying trees. The decreasing number of large ashes and oaks, and the lack of natural regeneration of the latter species, may negatively affect the middle spotted woodpecker in the future.     

Changes and availability of P fractions following 65 years of P application to a calcareous soil in a Mediterranean climate

The fate and availability of P derived from granular fertilisers in an alkaline Calcarosol soil were examined in a 65-year field trial in a semi-arid environment (annual rainfall 325 mm). Sequential P fractionation was conducted in the soils collected from the trial plots receiving 0–12 kg P ha⁻¹crop⁻¹, and the rhizosphere soil after growing wheat (Triticum aestivum L. cv. Yitpi) and chickpea (Cicer arietinum L. cv. Genesis 836) for one or two 60-day cycles in the glasshouse. Increasing long-term P application rate over 65 years significantly increased all inorganic P (Pi) fractions except HCl–Pi. By contrast, P application did not affect or tended to decrease organic P (Po) fractions. Increasing P application also increased Olsen-P and resin-P but decreased the P buffer capacity and sorption maxima. Residual P, Pi and Po fractions accounted for an average of 32, 16 and 52% of total P, respectively. All soil P fractions including residual P in the rhizosphere soil declined following 60-day growth of either wheat or chickpea. The decreases were greater in soils with a history of high P application than low P. An exception was water-extractable Po, which increased following plant growth. Changes in various P fractions in the rhizosphere followed the same pattern for both plant species. Biomass production and P uptake of the plants grown in the glasshouse correlated positively with the residual P and inorganic fractions (except HCl–Pi) but negatively with Po in the H₂O-, NaOH- and H₂SO₄-fractions of the original soils. The results suggest that the long-term application of fertiliser P to the calcareous sandy soil built up residual P and non-labile Pi fractions, but these P fractions are potentially available to crops.     

Patterns and rates of erosion in dead Porites across the Great Barrier Reef (Australia) after 2 years and 4 years of exposure

Rates and agents of erosion were investigated experimentally at six sites located along a cross shelf transect from the northern Queensland coast out into the Coral Sea. Rates of internal and external erosion of coral blocks, and accretion by coralline algae were measured after 2 years and 4 years of exposure. Blocks were cut from live colonies of Porites sp., which were collected from the outer barrier reef in north Queensland. They were then washed, dried, measured, weighed and attached to grids that were firmly attached to dead coral substrate at depths of 7–10 m. Significant differences in all three parameters were found within and among sites, and rates increased with increasing duration of exposure. Inshore sites were characterized by low rates of external erosion compared to offshore sites. Agents responsible for internal erosion differed among sites, with boring sponges being most abundant on the two inshore reefs, and molluscs most abundant at the offshore sites. Deposit-feeding polychaetes were more abundant at the two inshore sites, while filter and surface deposit feeders were more common at the offshore sites. Net erosion rates varied among sites (1.090±0.499 to 7.846±3.218 kg m²), and the relative importance of the components of erosion changed markedly along the cross-shelf transect.     

Cryptosporidiosis in children from 1 to 2 years of age, with acute diarrhea in Belém, Pará, Brazil

Two hundred and one samples obtained from 61 children were examined for Cryptosporidium infection during a period of 12 months. One hundred fifteen specimens were collected during diarrhoea episodes and the remaining 86 obtained out of diarrhoea period, as controls. All samples were examined by a modified Ziehl-Neelsen staining method. Cryptosporidium was detected in 6 (5.2%) of 115 samples from diarrhoeic children. All non-diarrhoeic control patients were negative for Cryptosporidium. The present study suggests that Cryptosporidium is an agent of self-limited diarrhoea among immunocompetent children from Belém, Pará.