Effect of aging on neuroglobin expression in rodent brain

Neuroglobin (Ngb), a recently discovered O2-binding heme protein related to hemoglobin and myoglobin, protects neurons from hypoxic-ischemic injury in vitro and in vivo. In immunostained mouse brain sections, we found widespread expression of Ngb protein in neurons, but not astrocytes, of several brain regions that are prominently involved in age-related neurodegenerative disorders. Western blots from young adult (3 month), middle-aged (12 month), and aged (24 month) rats showed an age-related decline in Ngb expression in cerebral neocortex, hippocampus, caudate-putamen, and cerebellum. Loss of this neuroprotective protein may have a role in increasing susceptibility to age-related neurological disorders.     

Quantifying the Ripple Effects of Civil War: How Armed Conflict Is Associated with More Severe Violence in the Home

Both the fields of public health and that of human rights seek to improve human well-being, including through reducing and preventing all forms of violence, to help individuals attain the highest quality of life. In both fields, mathematical methods can help “visibilize” the hidden architecture of violence, bringing new methods to bear to understand the scope and nuance of how violence affects populations. An increasing number of studies have examined how residing in a conflict-affected place may impact one of the most pervasive forms of violence—intimate partner violence (IPV)—during and after conflict. This paper contributes to this effort by examining whether severe forms of IPV are associated with previous experience of political violence in one conflict-affected country: Liberia. Our findings indicate that living in a district with conflict fatalities increased the risk of IPV among women by roughly 60%. Additionally, living in a district with conflict fatalities increased the risk of a past-year injury from IPV by 50%. This analysis brings to light links between two of the most pervasive forms of violence—political violence and violence against women. The findings suggest that women residing in a district that is more highly affected by conflict, not only people experiencing direct trauma during conflict, may be at risk of increased violence long after peace is declared. These findings point to the need for targeted programs that address IPV postconflict.     

Heterogeneity of toxicant response: sources of human variability.

While risk assessment models attempt to predict human risk to toxicant exposure, in many cases these models cannot account for the wide variety of human responses. This review addresses several primary sources of heterogeneity that may affect individual responses to drug or toxicant exposure. Consideration was given to genetic polymorphisms, age-related factors during development and senescence, gender differences associated with hormonal function, and preexisting diseases influenced by toxicant exposure. These selected examples demonstrate the need for additional steps in risk assessment that are needed to more accurately predict human responses to toxicants and drugs.     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.     

Accuracy and reliability of forensic handwriting comparisons

Forensic handwriting examination involves the comparison of writing samples by forensic document examiners (FDEs) to determine whether or not they were written by the same person. Here we report the results of a large-scale study conducted to assess the accuracy and reliability of handwriting comparison conclusions. Eighty-six practicing FDEs each conducted up to 100 handwriting comparisons, resulting in 7,196 conclusions on 180 distinct comparison sets, using a five-level conclusion scale. Erroneous “written by” conclusions (false positives) were reached in 3.1% of the nonmated comparisons, while 1.1% of the mated comparisons yielded erroneous “not written by” conclusions (false negatives). False positive rates were markedly higher for nonmated samples written by twins (8.7%) compared to nontwins (2.5%). Notable associations between training and performance were observed: FDEs with less than 2 y of formal training generally had higher error rates, but they also had higher true positive and true negative rates because they tended to provide more definitive conclusions; FDEs with at least 2 y of formal training were less likely to make definitive conclusions, but those definitive conclusions they made were more likely to be correct (higher positive predictive and negative predictive values). We did not observe any association between writing style (cursive vs. printing) and rates of errors or incorrect conclusions. This report also provides details on the repeatability and reproducibility of conclusions, and reports how conclusions are affected by the quantity of writing and the similarity of content.

Forensic science is under scrutiny, particularly for pattern-based disciplines in which source conclusions are reported. The National Research Council report Strengthening Forensic Science in the United States: A Path Forward (1) stated that “The scientific basis for handwriting comparisons needs to be strengthened” and noted that “there has been only limited research to quantify the reliability and replicability of the practices used by trained document examiners.” The President’s Council of Advisors on Science and Technology (PCAST) report Forensic Science in Criminal Courts: Ensuring Scientific Validity of Feature-Comparison Methods (2) expressed concerns regarding the validity and reliability of conclusions made by forensic examiners, and called for empirical testing: “The only way to establish the scientific validity and degree of reliability of a subjective forensic feature-comparison method—that is, one involving significant human judgment—is to test it empirically by seeing how often examiners actually get the right answer. Such an empirical test of a subjective forensic feature-comparison method is referred to as a ‘black-box test.’” The National Commission on Forensic Science also called for such testing (3). Although the accuracy and reliability of conclusions made by forensic document examiners (FDEs) have been the focus of multiple studies over the years (4–10), the designs of those studies are notably different from this study (and from PCAST’s recommendations), and therefore the resulting rates are not directly comparable (in particular, when comparing open-set to closed-set studies, comparing studies based on one-to-one vs. one-to-many examinations, and comparing studies that use notably different conclusion scales; see SI Appendix, Appendix B for a summary).This study was conducted to provide data that can be used to assess the scientific validity of handwriting comparisons, for use by policy makers, laboratory managers, the legal community, and FDEs. This study follows the approach used in the previous FBI Laboratory–Noblis latent print black box study (11) and later recommended by the PCAST report. The design utilizes open-set, one-to-one document comparisons to evaluate the conclusions reached by practicing FDEs when comparing writing samples selected to be broadly comparable to casework. The primary purposes of the study are to measure the accuracy of conclusions by FDEs when comparing handwriting samples and to assess reliability by measuring the reproducibility (interexaminer variability) and repeatability (intraexaminer variability) of those conclusions. Secondary purposes include reporting any associations between the accuracy of the decisions in this study, factors related to the participants (such as training or experience), and factors related to the samples (such as quantity of writing, comparability of content, limitations, or style of writing).     

Circulating serum xenoestrogens and mammographic breast density

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P_trend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P_trend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.