Securing the Internet of Healthcare

Cybersecurity, including the security of information technology (IT), is a critical requirement in ensuring society trusts, and therefore can benefit from, modern technology. Problematically, though, rarely a day goes by without a news story related to how critical data has been exposed, exfiltrated, or otherwise inappropriately used or accessed as a result of supply chain vulnerabilities. From the Russian government\u27s campaign to influence the 2016 U.S. presidential election to the September 2017 Equifax breach of more than 140-million Americans\u27 credit reports, mitigating cyber risk has become a topic of conversation in boardrooms and the White House, on Wall Street and Main Street. But oftentimes these discussions miss the problems replete in the often-expansive supply chains on which many of these products and services we depend on are built; this is particularly true in the medical device context. The problem recently made national news with the FDA-mandated recall of more than 400,000 pacemakers that were found to be vulnerable to hackers necessitating a firmware update. This Article explores the myriad vulnerabilities in the supply chain for medical devices, investigates existing FDA cybersecurity and privacy regulations to identify any potential governance gaps, and suggests a path forward to boost cybersecurity due diligence for manufacturers by making use of new approaches and technologies, including blockchain

Monitoring the health of transgender and other gender minority populations: Validity of natal sex and gender identity survey items in a U.S. national cohort of young adults

Background: A barrier to monitoring the health of gender minority (transgender) populations is the lack of brief, validated tools with which to identify participants in surveillance systems. Methods: We used the Growing Up Today Study (GUTS), a prospective cohort study of U.S. young adults (mean age = 20.7 years in 2005), to assess the validity of self-report measures and implement a two-step method to measure gender minority status (step 1: assigned sex at birth, step 2: current gender identity). A mixed-methods study was conducted in 2013. Construct validity was evaluated in secondary data analysis of the 2010 wave (n = 7,831). Cognitive testing interviews of close-ended measures were conducted with a subsample of participants (n = 39). Results: Compared to cisgender (non-transgender) participants, transgender participants had higher levels of recalled childhood gender nonconformity age < 11 years and current socially assigned gender nonconformity and were more likely to have ever identified as not completely heterosexual (p < 0.001). No problems with item comprehension were found for cisgender or gender minority participants. Assigned sex at birth was interpreted as sex designated on a birth certificate; transgender was understood to be a difference between a person’s natal sex and gender identity. Participants were correctly classified as male, female, or transgender. Conclusions: The survey items performed well in this sample and are recommended for further evaluation in languages other than English and with diverse samples in terms of age, race/ethnicity, and socioeconomic status

Risk of myocardial infarction and ischemic stroke in individuals with first-diagnosed paroxysmal vs. non-paroxysmal atrial fibrillation under anticoagulation

AimsThere is conflicting evidence on whether the type of atrial fibrillation (AF) is associated with risk of cardiovascular events, including acute myocardial infarction (MI) and ischemic stroke. The aim of the present study was to investigate whether the risk of MI and ischemic stroke differs between individuals with first-diagnosed paroxysmal vs. non-paroxysmal AF treated with anticoagulants.Methods and resultsDe-identified electronic medical records from the TriNetX federated research network were used. Individuals with a new diagnosis of paroxysmal AF who had no evidence of other types of AF in their records were 1:1 propensity score-matched with individuals with non-paroxysmal AF, defined as persistent or chronic AF, who had no evidence of other types of AF in their records. All patients were followed for three years for the outcomes of MI and ischemic stroke. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). In the propensity-matched cohort, among 24 848 well-matched AF individuals [mean age 74.4 ± 10.4; 10 101 (40.6%) female], 410 (1.7%) were diagnosed with acute MI and 875 (3.5%) with ischemic stroke during the three-year follow-up. Individuals with paroxysmal AF had significantly higher risk of acute MI (HR: 1.65, 95%CI: 1.35-2.01) compared to those with non-paroxysmal AF. First diagnosed paroxysmal AF was associated with higher risk of non-ST elevation MI (nSTEMI) (HR: 1.89, 95%CI: 1.44-2.46). No significant association was observed between the type of AF and risk of ischemic stroke (HR: 1.09, 95%CI: 0.95-1.25).ConclusionPatients with first-diagnosed paroxysmal AF had higher risk of acute MI compared to individuals with non-paroxysmal AF, attributed to the higher risk of nSTEMI among patients with first-diagnosed paroxysmal AF. There was no significant association between type of AF and risk of ischemic stroke

Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response

Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3+, CD8+ and CD3+ cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response

Automation-Induced Complacency Potential: Development and Validation of a New Scale

Complacency, or sub-optimal monitoring of automation performance, has been cited as a contributing factor in numerous major transportation and medical incidents. Researchers are working to identify individual differences that correlate with complacency as one strategy for preventing complacency-related accidents. Automation-induced complacency potential is an individual difference reflecting a general tendency to be complacent across a wide variety of situations which is similar to, but distinct from trust. Accurately assessing complacency potential may improve our ability to predict and prevent complacency in safety-critical occupations. Much past research has employed an existing measure of complacency potential. However, in the 25 years since that scale was published, our conceptual understanding of complacency itself has evolved, and we propose that an updated scale of complacency potential is needed. The goal of the present study was to develop, and provide initial validation evidence for, a new measure of automation-induced complacency potential that parallels the current conceptualization of complacency. In a sample of 475 online respondents, we tested 10 new items and found that they clustered into two separate scales: Alleviating Workload (which focuses on attitudes about the use of automation to ease workloads) and Monitoring (which focuses on attitudes toward monitoring of automation). Alleviating workload correlated moderately with the existing complacency potential rating scale, while monitoring did not. Further, both the alleviating workload and monitoring scales showed discriminant validity from the previous complacency potential scale and from similar constructs, such as propensity to trust. In an initial examination of criterion-related validity, only the monitoring-focused scale had a significant relationship with hypothetical complacency (r = -0.42, p &lt; 0.01), and it had significant incremental validity over and above all other individual difference measures in the study. These results suggest that our new monitoring-related items have potential for use as a measure of automation-induced complacency potential and, compared with similar scales, this new measure may have unique value

Infarct Location and Sleep Apnea: Evaluating the Potential Association in Acute Ischemic Stroke.

Background: The literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. Methods: Data were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. Results: Among 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. Conclusions: These results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients

No Effect of Exercise Intensity on Appetite in Highly-Trained Endurance Women

In endurance-trained men, an acute bout of exercise is shown to suppress post-exercise appetite, yet limited research has examined this response in women. The purpose of this study was to investigate the effect of exercise intensity on appetite and gut hormone responses in endurance-trained women. Highly-trained women (n = 15, 18–40 years, 58.4 ± 6.4 kg, VO₂ₘₐₓ = 55.2 ± 4.3 mL/kg/min) completed isocaloric bouts (500 kcals or 2093 kJ) of moderate-intensity (MIE, 60% VO2MAX) and high-intensity (HIE, 85% VO2MAX) treadmill running at the same time of day, following a similar 48-h diet/exercise period, and at least 1-week apart. Blood was drawn pre-exercise (baseline), immediately post-exercise and every 20-min for the next 60-min. Plasma concentrations of acylated ghrelin, PYY₃₋₃₆, GLP-1 and subjective appetite ratings via visual analog scale (VAS) were assessed at each time point. Acylated ghrelin decreased (p = 0.014) and PYY3–36 and GLP-1 increased (p = 0.036, p < 0.0001) immediately post-exercise, indicating appetite suppression. VAS ratings of hunger and desire to eat decreased immediately post-exercise (p = 0.0012, p = 0.0031, respectively), also indicating appetite suppression. There were no differences between exercise intensities for appetite hormones or VAS. Similar to males, post-exercise appetite regulatory hormones were altered toward suppression in highly-trained women and independent of energy cost of exercise. Results are important for female athletes striving to optimize nutrition for endurance performance

Importance of Indigenous Peoples' lands for the conservation of Intact Forest Landscapes

Intact Forest Landscapes (IFLs) are critical strongholds for the environmental services that they provide, not least for their role in climate protection. On the basis of information about the distributions of IFLs and Indigenous Peoples’ lands, we examined the importance of these areas for conserving the world's remaining intact forests. We determined that at least 36% of IFLs are within Indigenous Peoples’ lands, making these areas crucial to the mitigation action needed to avoid catastrophic climate change. We also provide evidence that IFL loss rates have been considerably lower on Indigenous Peoples’ lands than on other lands, although these forests are still vulnerable to clearing and other threats. World governments must recognize Indigenous Peoples’ rights, including land tenure rights, to ensure that Indigenous Peoples play active roles in decision‐making processes that affect IFLs on their lands. Such recognition is critical given the urgent need to reduce deforestation rates in the face of escalating climate change and global biodiversity loss.Intact Forest Landscapes (IFLs) are critical strongholds for the environmental services that they provide, not least for their role in climate protection. On the basis of information about the distributions of IFLs and Indigenous Peoples' lands, we examined the importance of these areas for conserving the world's remaining intact forests. We determined that at least 36% of IFLs are within Indigenous Peoples' lands, making these areas crucial to the mitigation action needed to avoid catastrophic climate change. We also provide evidence that IFL loss rates have been considerably lower on Indigenous Peoples' lands than on other lands, although these forests are still vulnerable to clearing and other threats. World governments must recognize Indigenous Peoples' rights, including land tenure rights, to ensure that Indigenous Peoples play active roles in decision-making processes that affect IFLs on their lands. Such recognition is critical given the urgent need to reduce deforestation rates in the face of escalating climate change and global biodiversity loss.Peer reviewe

A long-term record of early to mid-Paleozoic marine redox change

The extent to which Paleozoic oceans differed from Neoproterozoic oceans and the causal relationship between biological evolution and changing environmental conditions are heavily debated. Here, we report a nearly continuous record of seafloor redox change from the deep-water upper Cambrian to Middle Devonian Road River Group of Yukon, Canada. Bottom waters were largely anoxic in the Richardson trough during the entirety of Road River Group deposition, while independent evidence from iron speciation and Mo/U ratios show that the biogeochemical nature of anoxia changed through time. Both in Yukon and globally, Ordovician through Early Devonian anoxic waters were broadly ferruginous (nonsulfidic), with a transition toward more euxinic (sulfidic) conditions in the mid–Early Devonian (Pragian), coincident with the early diversification of vascular plants and disappearance of graptolites. This ~80-million-year interval of the Paleozoic characterized by widespread ferruginous bottom waters represents a persistence of Neoproterozoic-like marine redox conditions well into the Phanerozoic

A 44-Nucleotide Region in the Chikungunya Virus 3′ UTR Dictates Viral Fitness in Disparate Host Cells

We previously reported that deletion of a 44-nucleotide element in the 3′ untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination. Finally, SHAPE-MaP analysis of the CHIKV 3′ UTR revealed this 44-nucleotide element forms a distinctive two-stem-loop structure that is ablated in the mutant 3′ UTR without altering additional 3′ UTR RNA secondary structures