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The United States has a long and controversial history with abortion that did not end with Roe v. Wade. Almost immediately thereafter, anti-choice politicians commenced a decades-long effort to restrict access to abortion, recently culminating in the Dobbs decision that overturned Roe. One successful attempt to restrict access immediately following Roe was the Hyde Amendment. With more Americans covered by federally funded health insurance than ever, the Hyde Amendment creates an insurmountable barrier to abortion care for those who lack other sources of financing.
Despite the impacts of the Hyde Amendment, support for discontinuing the amendment has been weak. For the first time in over forty years, the United States is in a position to change its abortion funding policy. Beyond ending Hyde, the EACH Act has been introduced in Congress to ensure permanent funding for abortion through all federally funded insurance programs. To secure funding for abortion and reduce barriers to access, advocates must press the federal government to pass legislation such as the EACH Act.
Background: Chordomas are rare malignant skull-base/spine cancers with devastating neurological morbidities and mortality. Unfortunately, no reliable prognostic factors exist to guide treatment decisions. This work identifies DNA methylation-based prognostic chordoma subtypes that are detectable non-invasively in plasma. Methods: Sixty-eight tissue samples underwent DNA methylation profiling and plasma methylomes were obtained for available paired samples. Immunohistochemical staining and publicly available methylation and gene expression data were utilized for validation. Results: Unsupervised clustering identified two prognostic tissue clusters (log-rank p=0.0062) predicting disease-specific survival independent of clinical factors (Multivariable Cox: HR=16.5, 95%CI: 2.8-96, p=0.0018). The poorer-performing cluster showed immune-related pathway promoter hypermethylation and higher immune cell abundance within tumours, which was validated with external RNA-seq data and immunohistochemical staining. The better-performing cluster showed higher tumour cellularity. Similar clusters were seen in external DNA methylation data. Plasma methylome-based models distinguished chordomas from differential diagnoses in independent testing sets (AUROC=0.84, 95%CI: 0.52-1.00). Plasma methylomes were highly correlated with tissue-based signals for both clusters (r=0.69 & 0.67) and leave-one-out models identified the correct cluster in all plasma cases. Conclusions: Prognostic molecular chordoma subgroups are for the first time identified, characterized, and validated. Plasma methylomes can detect and subtype chordomas which may transform chordoma treatment with personalized approaches tailored to prognosis.
There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers.
Method
This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy).
Results
Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years.
Conclusion
Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.
Nanocrystalline oxides are mainly responsible for Ni-base oxide dispersion strengthened (ODS) superalloys excellent thermo-mechanical properties. To establish the microstructural correlations between the metallic matrix and various oxide dispersoids, we report here the atomic-scale structure and chemistry of the complex nano-oxide dispersoids. Ultrahigh-resolution Cs-aberration-corrected scanning transmission electron microscopy (STEM) based techniques have been used to resolve nano-dispersoids in the Alloy 617 ODS. These nano-oxides, interestingly, possess a variety of high-angle annular dark-field (HAADF) contrasts, that is, bright, dark, and bi-phases. Both the light and heavy atoms have been found to be present in Y–Al–O complex-oxide nanostructures in varying quantities and forming a characteristic interface with the metallic matrix. In overcoming the limitation of conventional STEM-HAADF imaging, the integrated differential phase-contrast imaging technique was employed to investigate the oxygen atoms along with other elements in the dispersoids and its interface with the matrix. The most intriguing aspect of the study is the discovery of a few atoms thick Al2O3 interlayer (shell) around a monoclinic Y–Al–O core in the Ni-matrix. On the other hand, when the dispersoid is a hexagonal type Y–Al–O complex, the interface energy is already low, maintaining a semi-coherent interface and it was devoid of a shell.
Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
Binaural hearing is facilitated by neural interactions in the auditory pathway. Ageing results in impairment of localisation and listening in noisy situations without any significant hearing loss. The present study focused on comparing the binaural encoding of a speech stimulus at the subcortical level in middle-aged versus younger adults, based on speech-evoked auditory brainstem responses.
Methods
Thirty participants (15 young adults and 15 middle-aged adults) with normal hearing sensitivity (less than 15 dB HL) participated in the study. The speech-evoked auditory brainstem response was recorded monaurally and binaurally with a 40-ms /da/ stimulus. Fast Fourier transform analysis was utilised.
Results
An independent sample t-test revealed a significant difference between the two groups in fundamental frequency (F0) amplitude recorded with binaural stimulation.
Conclusion
The present study suggested that ageing results in degradation of F0 encoding, which is essential for the perception of speech in noise.
Introduction: The Maximizing Aging Using Volunteer Engagement in the ED (MAUVE + ED) program connects specially trained volunteers with older patients whose personal and social needs are not always met within the busy ED environment. The objective of this study was to describe the development and implementation of the MAUVE + ED program and the activities performed with older patients by its volunteers. Methods: The MAUVE + ED program was implemented in the ED (annual census 65,000) of a large academic tertiary hospital in Toronto, Ontario. Volunteers were trained to identify and approach older patients and others at greater risk for adverse outcomes, including poor patient experience, in the ED and invite such patients to participate in the program. The program is available to all patients >65 years, and those with confusion, patients who were alone, those with mobility issues, and patients with increased length of stay in the ED. Volunteers documented their activities after each patient encounter using a standardized paper-based data collection form. Results: Over the program's initial 6-month period, the MAUVE + ED volunteers reported a total of 896 encounters with 718 unique patients. The median (IQR) time a MAUVE volunteer spent with a patient was 10 (5, 20) minutes, with a range of 1 to 130 minutes. The median (IQR) number of patients seen per shift was 7 (6, 9), with a range of 1 to 16 patients per shift. The most common activities the volunteer assisted with were therapeutic activities/social visits (n = 859; 95.9%), orientation activities (n = 501; 55.9%), and hydration assistance (n = 231; 25.8%). The least common were mobility assistance (n = 36; 4.0%), and vision/hearing assistance (n = 13; 1.5%). Conclusion: Preliminary data suggest the MAUVE + ED volunteers were able to enrich the experience of older adults and their families/carers in the ED.
Intellectual disability (ID) is defined as significantly subaverage intellectual functioning with deficits in adaptive behavior. For ∼40% of individuals, cause for disability remains unknown and these are categorized as idiopathic ID (IID). Various behavioral problems co-occur with ID and thus serotonergic neurotransmission, known to control emotion, mood and drive, has received immense attention. Synaptic serotonin (5-HT) level is primarily maintained by metabolizing enzyme MAOA and serotonin transporter (SLC6A4) which helps in reuptake of the neurotransmitter. Since functional genetic polymorphisms have a potency to affect activities of these proteins, in the present investigation polymorphisms in these genes (MAOA-u VNTR, rs6323, 5-HTTLPR and STIN2) have been analyzed in IID individuals associated with various behavioral problems.
Methods
Families (N=189) with IID probands were recruited following DSM-IV. After obtaining informed written consent for participation, peripheral blood was collected for isolation of genomic DNA used for PCR-based genotyping of target sites followed by family-based statistical analyses of data.
Results
Significant association of MAOA rs6323 “T” allele with female IID (P=0.016) and a trend towards association with female IID patients exhibiting behavioral problems (P=0.046) was noticed. Non significant over transmission of the 5-HTTLPR “L” allele was also observed in female IID probands with behavioral problems (P=0.076). Synergistic epistatic interaction, with a sex-bias, was noticed between MAOA and 5-HTT (P< 0.05).
Conclusions
From the data obtained it could be summarized that serotonergic system may have some role in the etiology of behavioral problems of female IID individuals.
The prime focus of this work is to estimate stability and control derivatives of an airship in a completely nonlinear environment. A complete six degrees of freedom airship model has its aerodynamic model as nonlinear functions of angle of attack. Estimating the parameters of aerodynamic model in a nonlinear environment is challenging as it demands an exhaustive dataset that could cover the entire regime of operation of airship. In this work, data generation is achieved by simulating the mathematical model of airship for different trim conditions obtained from continuation analysis. The mathematical model is simulated using predicted parameter values obtained using DATCOM methodology. A modular neural network is then trained using back-propagation and Adam optimisation algorithm for each of the aerodynamic coefficients separately. The estimated nonlinear airship parameters are found to be consistent with the DATCOM parameter values which were used for open-loop simulation. This validates the proposed methodology and could be extended to estimate airship parameters from real flight data.
Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.
A cross-sectional study was conducted from 2014 to 2017 in 13 organised pig farms located in eight states of India (Northern, North-Eastern and Southern regions) to identify the risk factors, pathotype and antimicrobial resistance of Escherichia coli associated with pre- and post-weaning piglet diarrhoea. The data collected through questionnaire survey were used to identify the risk factors by univariable analysis, in which weaning status, season, altitude, ventilation in the shed, use of heater/cooler for temperature control in the sheds, feed type, water source, and use of disinfectant, were the potential risk factors. In logistic regression model, weaning and source of water were the significant risk factors. The piglet diarrhoea prevalence was almost similar across the regions. Of the 909 faecal samples collected (North – 310, North-East – 194 and South – 405) for isolation of E. coli, pathotyping and antibiotic screening, 531 E. coli were isolated in MacConkey agar added with cefotaxime, where 345 isolates were extended spectrum β-lactamase (ESBL) producers and were positive for blaCTX-M-1 (n = 147), bla TEM (n = 151), qnrA (n = 98), qnrB (n = 116), qnrS (n = 53), tetA (n = 46), tetB (n = 48) and sul1 (n = 54) genes. Multiple antibiotic resistance (MAR) index revealed that 14 (2.64%) isolates had MAR index of 1. On the virulence screening of E. coli, 174 isolates harboured alone or combination of Stx1, Stx2, eaeA, hlyA genes. The isolates from diarrhoeic and post-weaning samples harboured higher number of virulence genes than non-diarrhoeic and pre-weaning. Alleviating the risk factors might reduce the piglet diarrhoea cases. The presence of multidrug-resistant and ESBL-producing pathogenic E. coli in piglets appears a public health concern.
A cross-sectional study on six dairy farms was conducted to ascertain the occurrence of carbapenem-resistant Escherichia coli in calves. Two-hundred and seventy-nine isolates of E. coli were recovered from 90 faecal samples from apparently healthy (45) and diarrhoeal (45) calves. The isolates were screened for phenotypic susceptibility to carbapenems and production of metallo β-lactamase, as well as five carbapenemase resistance genes by PCR, and overexpression of efflux pumps. Eighty-one isolates (29.03%) were resistant to at least one of three carbapenem antibiotics [meropenem (23.30%), imipenem (2.15%) and ertapenem (1.43%)], and one isolate was positive for the blaVIM gene which was located on an Incl1 plasmid of a novel sequence type (ST 297) by multilocus sequence typing. The majority (83.95%) of isolates had an active efflux pump. Calves housed on concrete floors were approximately seven times more likely to acquire meropenem-resistant isolates than those housed on earthen floors (95% CI 1.27–41.54). In India, carbapenem drugs are not used in food animal treatment, hence carbapenem-resistant strains in calves possibly originate from the natural environment or human contact and is of public health importance. To our knowledge, this is the first report of blaVIM carbapenemases gene in calves from India.
A novel microfilarial sheath protein (MfP) of the human filarial parasite Wuchereria bancrofti and its proinflammatory activity on host macrophages were identified recently. MfP is a homolog of the nematode bestrophin-9 superfamily that acts as a ligand of macrophage Toll-like receptor 4 (TLR4) to induce inflammation through NF-κB activation. Therefore, the presence and functional implication of this novel protein in adult-stage parasites were open questions to answer. In this study, the bovine filarial parasite Setaria cervi was used to simulate adult W. bancrofti. We detected the presence of MfP in adult-stage S. cervi through clear immunological cross-reactivity and immunolocalization employing an anti-MfP antibody developed in mice. Therefore, our findings put forward S. cervi as a cost-effective source of immunodominant filarial antigen MfP to simulate its future utilization in the immunotherapeutic intervention of lymphatic filariasis.