Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids.

The repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain. Morphogens crosstalk translated into early patterns of gene expression programs predicting the generation of specific brain lineages. Human iPSC lines from six different genetic backgrounds showed substantial differences in response to morphogens, suggesting that interindividual genomic and epigenomic variations could impact brain lineages formation. Morphogen gradients promise to be a key approach to model the brain in its entirety.

Perspectives on Electronic Nicotine Delivery System Use Cessation Among Adults in Rural Areas: Implications for Future Studies.

INTRODUCTION: More young adults (age 18-24 years) in rural areas versus urban areas use electronic nicotine delivery systems (ENDS) - also known as e-cigarettes. Little is known about young adults' perceptions toward ENDS use and cessation. The objective of this study was to examine barriers and facilitators to ENDS use cessation among young adults living in rural areas, as well as their perceptions about ENDS use and cessation and to determine implications for future cessation studies. METHODS: We administered cross-sectional online surveys to young adults living in rural Midwestern counties. A total of 100 individuals responded to the surveys. Descriptive statistics were used to report their perceptions of ENDS use as well as barriers and facilitators to ENDS use cessation. The content analysis method was used to analyze the answers to an open-ended question regarding perceptions about the ENDS use cessation in the context of rural areas. RESULTS: Barriers to ENDS use cessation included perceived advantages to ENDS use, high nicotine dependence, and the perception that ENDS use was less harmful cigarettes. Facilitators to ENDS use cessation included cost of ENDS use, perceived harm, and high confidence in ability to quit. Participants' perceptions about ENDS use cessation in the context of rural areas were conceptualized under the themes of (1) exposure to and initiation of ENDS use, (2) continuation of ENDS use, and (3) prevention and cessation of ENDS use. CONCLUSIONS: Health care providers, tobacco control researchers, and public health advocates should be aware of barriers and facilitators to ENDS use cessation among young adults for future cessation intervention studies relevant specifically to rural areas.

Racial and ethnic differences in post-traumatic stress trajectories in breast cancer survivors.

PURPOSE: To describe differences in post-traumatic stress (PTS) symptoms over time among racial and ethnic minoritized breast cancer survivors (BCS) with comorbid diabetes. DESIGN: In a multisite longitudinal study, post-traumatic stress was evaluated at baseline, 6 and 12 months through self-reported questionnaires (Impact of Events Scale-Revised [IES-R]). PARTICIPANTS: One hundred and seventy-eight post-treatment BCS with diabetes were recruited from three tertiary medical centers. FINDINGS: Relative to non-Hispanic White women, minoritized women reported higher total IES-R scores at all time points. In the adjusted model, Latina women reported persistently higher IES-R total scores and Latina, and 'Other' women reported higher avoidance scores. CONCLUSIONS: Minoritized BCS with comorbid diabetes report higher rates of cancer related PTS that persist over 12 months. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Post diagnosis PTS evaluation and support is important in survivorship and primary care practices. Linkage to socially and culturally sensitive community support may be warranted.

Client Desires and the Price of Seduction: Exploring the Relationship Between Independent Escorts' Marketing and Rates.

This article explores Web site content and differences in advertised rates among a sample of 839 independent female online escorts operating their own Web sites in major metropolitan areas in the United States. Statistical analyses of escorts' rates indicate pricing variation across cities in which escorts advertise; the number of cities and Websites in which they advertise; whether they travel to areas beyond their primary locality to meet clients; their age and stated racial/ethnic/sexual identity; the Internet platforms on which they advertise; and how they present themselves and their services on their Web pages. These relationships between business strategies of independent escorts and their published rates shed light on client preferences and market demand. Our findings provide important new insights into independent online escorts' business strategies and financial tactics and identify factors impacting perceived market value for escort services. This research supports emerging literature indicating that clients of independent online escorts will pay more for particular provider characteristics, dispositions, and services, and they most highly value erotic services that are seductive and mirror the qualities of nonremunerative sexual exchange, often described as the "girlfriend experience" (GFE).

Coordinated Assembly of the Bacillus anthracis Coat and Exosporium during Bacterial Spore Outer Layer Formation.

Bacterial spores produced by the Bacillales are composed of concentric shells, each of which contributes to spore function. Spores from all species possess a cortex and coat, but spores from many species possess additional outer layers. The outermost layer of Bacillus anthracis spores, the exosporium, is separated from the coat by a gap known as the interspace. Exosporium and interspace assembly remains largely mysterious. As a result, we have a poor understanding of the overarching mechanisms driving the assembly of one of the most ubiquitous cell types in nature. To elucidate the mechanisms directing exosporium assembly, we generated strains bearing mutations in candidate exosporium-controlling genes and analyzed the effect on exosporium formation. Biochemical and cell biological analyses argue that CotE directs the assembly of CotO into the spore and that CotO might be located at or close to the interior side of the cap. Taken together with data showing that CotE and CotO interact directly in vitro, we propose a model in which CotE and CotO are important components of a protein interaction network that connects the exosporium to the forespore during cap formation and exosporium elongation. Our data also suggest that the cap interferes with coat assembly at one pole of the spore, altering the pattern of coat deposition compared to the model organism Bacillus subtilis We propose that the difference in coat assembly patterns between these two species is due to an inherent flexibility in coat assembly, which may facilitate the evolution of spore outer layer complexity.IMPORTANCE This work dramatically improves our understanding of the assembly of the outermost layer of the B. anthracis spore, the exosporium, a layer that encases spores from many bacterial species and likely plays important roles in the spore's interactions with the environment, including host tissues. Nonetheless, the mechanisms directing exosporium assembly into a shell surrounding the spore are still very poorly understood. In this study, we clarify these mechanisms by the identification of a novel protein interaction network that directs assembly to initiate at a specific subcellular location in the developing cell. Our results further suggest that the presence or absence of an exosporium has a major impact on the assembly of other more interior spore layers, thereby potentially explaining long-noted differences in spore assembly between B. anthracis and the model organism B. subtilis.

Vertically distinct microbial communities in the Mariana and Kermadec trenches.

Hadal trenches, oceanic locations deeper than 6,000 m, are thought to have distinct microbial communities compared to those at shallower depths due to high hydrostatic pressures, topographical funneling of organic matter, and biogeographical isolation. Here we evaluate the hypothesis that hadal trenches contain unique microbial biodiversity through analyses of the communities present in the bottom waters of the Kermadec and Mariana trenches. Estimates of microbial protein production indicate active populations under in situ hydrostatic pressures and increasing adaptation to pressure with depth. Depth, trench of collection, and size fraction are important drivers of microbial community structure. Many putative hadal bathytypes, such as members related to the Marinimicrobia, Rhodobacteraceae, Rhodospirilliceae, and Aquibacter, are similar to members identified in other trenches. Most of the differences between the two trench microbiomes consists of taxa belonging to the Gammaproteobacteria whose distributions extend throughout the water column. Growth and survival estimates of representative isolates of these taxa under deep-sea conditions suggest that some members may descend from shallower depths and exist as a potentially inactive fraction of the hadal zone. We conclude that the distinct pelagic communities residing in these two trenches, and perhaps by extension other trenches, reflect both cosmopolitan hadal bathytypes and ubiquitous genera found throughout the water column.

Do Different Types of Assets Have Differential Effects on Child Education?: Evidence from Tanzania.

To assess the conventional view that assets uniformly improve childhood development through wealth effects, this paper tests whether different types of assets have different effects on child education. The analysis indicates that household durables and housing quality have the expected positive effects, but agricultural assets have adverse effects on highest grade completed and no effects on exam performance. Extending the standard agricultural-household model by explicitly including child labor, the study uses three waves of panel data from Tanzania to estimate the effects of household assets on child education. The analysis corrects for the endogeneity of assets and uses a Hausman-Taylor instrumental variable panel data estimator to identify the effects of time-invariant observables and more efficiently control for time-invariant unobservables. The negative effect of agricultural assets is more pronounced among rural children and children from farming households, presumably due to the higher opportunity cost of their schooling.

Navigating Unmountable Media with the Digital Forensics XML File System.

Some computer storage is non-navigable by current general-purpose computers. This could be because of obsolete interface software, or a more specialized storage system lacking widespread support. These storage systems may contain artifacts of great cultural, historical, or technical significance, but implementing compatible interfaces may be beyond available resources. We developed the DFXML File System (DFXMLFS) to enable navigation of arbitrary storage systems that fulfill a minimum feature set of the POSIX file system standard. Our approach advocates for a two-step workflow that separates parsing the storage's file system structures from navigating the storage like a contemporary file system, including file contents. The parse extracts essential file system metadata, serializing to Digital Forensics XML for later consumption as a read-only file system.

Advancing Coordinated Cyber-investigations and Tool Interoperability using a Community Developed Specification Language.

Any investigation can have a digital dimension, often involving information from multiple data sources, organizations and jurisdictions. Existing approaches to representing and exchanging cyber-investigation information are inadequate, particularly when combining data sources from numerous organizations or dealing with large amounts of data from various tools. To perform digital investigations effectively, there is a pressing need to harmonize how information relevant to cyber-investigations is represented and exchanged. This paper addresses this need for information exchange and tool interoperability with an open community-developed specification language called Cyber-investigation Analysis Standard Expression (CASE). To further promote a common structure, CASE aligns with and extends the Unified Cyber Ontology (UCO) construct, which provides a format for representing information in all cyber domains. This ontology abstracts objects and concepts that are not CASE-specific, so that they can be used across other cyber disciplines that may extend UCO. This work is a rational evolution of the Digital Forensic Analysis eXpression (DFAX) for representing digital forensic information and provenance. CASE is more flexible than DFAX and can be utilized in any context, including criminal, corporate and intelligence. CASE also builds on the Hansken data model developed and implemented by the Netherlands Forensic Institute (NFI). CASE enables the fusion of information from different organizations, data sources, and forensic tools to foster more comprehensive and cohesive analysis. This paper includes illustrative examples of how CASE can be implemented and used to capture information in a structured form to advance sharing, interoperability and analysis in cyber-investigations. In addition to capturing technical details and relationships between objects, CASE provides structure for representing and sharing details about how cyber-information was handled, transferred, processed, analyzed, and interpreted. CASE also supports data marking for sharing information at different levels of trust and classification, as well as protection of sensitive and private information. Furthermore, CASE supports the sharing of knowledge related to cyber-investigations, including distinctive patterns of activity/behavior that are common across cases. This paper features a proof-of-concept implementation using the open source forensic framework named plaso to export data to CASE. Community members are encouraged to participate in the development and implementation of CASE and UCO.

The Importance of Animal Source Foods for Nutrient Sufficiency in the Developing World: The Zambia Scenario.

There have been successful interventions fortifying staple foods to mobilize micronutrients as well as agricultural efforts to raise yields of staple foods to increase food availability. Zambia serves as an interesting case study because since 1961 there has been a notable decline in the availability of animal source foods (ASFs) and pulses and a significant increase in the supply of cassava and vegetable oils. The shift in food availability was partly attributed to the agricultural success in high-yielding and drought-resistant varieties that made cassava and oil crops more affordable and readily available. In this research, we explore another policy strategy that involves ASF as a mechanism to help remedy micronutrient inadequacies in a population. A scenario modeling analysis compares the changes in the nutrient profile of the Zambian diet through adding either staple plant source foods (PSFs) or ASFs. The scenarios under study involve the addition of (1) 18 fl oz of whole cow's milk; (2) 60 g of beef, 30 g of chicken, and 5 g of beef liver; (3) milk plus meat; or (4) 83 g of maize flour, 123 g of cassava, and other staple PSF, that is, isocaloric to the "milk + meat" group. The findings alert program planners and policy makers to the value of increasing the availability, accessibility, and utilization of ASF to simultaneously address multiple nutrient deficiencies, as well as the nutrition challenges that remain when expanding the availability of plant-based staples.

Posttransplant lymphoproliferative disorder in an 11-year-old immunosuppressed boy.

We present an 11-year-old boy who presented with symptoms of subacute facial nerve palsy after cardiac transplant. Neuroimaging revealed multiple ring-enhancing lesions that were most concerning for opportunistic organism abscesses and he was treated with broad-spectrum antifungal and antibacterial therapy. After noninvasive testing failed to identify a causative organism, he underwent brain biopsy. Pathology revealed posttransplant lymphoproliferative disease that was later determined to be isolated to the central nervous system. The patient was treated with reduction in his immunotherapy and chemotherapy including rituximab and methotrexate. This case exemplifies the importance of having a low threshold to consider posttransplant lymphoproliferative disease in posttransplant patients.

Ankle injuries among United States high school sports athletes, 2005-2006.

CONTEXT: Ankle injuries are the most common sport-related injuries. To date, no studies have been published that use national data to present a cross-sport, cross-sex analysis of ankle injuries among US high school athletes. OBJECTIVE: To investigate the incidence rates of ankle injuries by sex, type of exposure, and sport. DESIGN: Descriptive epidemiologic study. SETTING: One hundred US high schools. PATIENTS OR OTHER PARTICIPANTS: United States high school athletes. MAIN OUTCOME MEASURE(S): We reviewed ankle injury data collected over the 2005-2006 school year from a nationally representative sample obtained by High School RIO, an injury surveillance system. Specific sports studied were boys' football, boys' and girls' soccer, girls' volleyball, boys' and girls' basketball, boys' wrestling, boys' baseball, and girls' softball. RESULTS: An estimated 326 396 ankle injuries occurred nationally in 2005-2006, yielding an injury rate of 5.23 ankle injuries per 10 000 athlete-exposures. Ankle injuries occurred at a significantly higher rate during competition (9.35 per 10 000 athlete-exposures) than during practice (3.63) (risk ratio = 2.58; 95% confidence interval = 2.26, 2.94; P < .001). Boys' basketball had the highest rate of ankle injury (7.74 per 10 000 athlete-exposures), followed by girls' basketball (6.93) and boys' football (6.52). In all sports except girls' volleyball, rates of ankle injury were higher in competition than in practice. Overall, most ankle injuries were diagnosed as ligament sprains with incomplete tears (83.4%). Ankle injuries most commonly caused athletes to miss less than 7 days of activity (51.7%), followed by 7 to 21 days of activity loss (33.9%) and more than 22 days of activity loss (10.5%). CONCLUSIONS: Sports that combine jumping in close proximity to other players and swift changes of direction while running are most often associated with ankle injuries. Future research on ankle injuries is needed to drive the development and implementation of more effective preventive interventions.

Noise reduction for heart sounds using a modified minimum-mean squared error estimator with ECG gating.

In this paper, we present a method for single channel noise reduction of heart sound recordings. Multiple noise sources, such as lung sounds, muscle contraction, and background noise can contaminate the heart sound collection making subsequent analysis difficult. Our approach is based on a spectral domain minimum-mean squared error (MMSE) estimation, originally introduced by Ephraim and Malah in the context of speech enhancement. This method uses a "decision-directed" approach to estimate the noise spectrum without the need for a separate reference signal. The noise spectrum is used to compute the SNR on-line for adapting the Wiener filter gain applied to the spectral amplitudes. A number of modifications are made to the baseline algorithm to increase the level of noise reduction while simultaneously reducing signal distortion. Enhancements include the use of a "soft" threshold to determine when to update the noise spectrum, a forward-backward filtering implementation (i.e., smoothing), and a "second-pass" iterative estimation scheme in which the residual noise is used to re-estimate the SNR and update the Wiener gains. In addition, ECG analysis is used to provide gating information on when desired heart sounds may be present in order to further guide the noise spectral estimation procedure. The noise reduction algorithm is tested as a front-end to an automatic heart sound analysis system. The sounds are collected through two sensors that act simultaneously as microphones and ECG electrodes. The proposed algorithm demonstrates improvements over existing noise reduction approaches in terms of SNR gain, qualitative evaluations, and automatic detection of abnormalities present in the heart sounds.