Rhesus macaques build new social connections after a natural disaster

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record. Climate change is increasing the frequency and intensity of weather-related disasters such as hurricanes, wildfires, floods, and droughts. Understanding resilience and vulnerability to these intense stressors and their aftermath could reveal adaptations to extreme environmental change. In 2017, Puerto Rico suffered its worst natural disaster, Hurricane Maria, which left 3,000 dead and provoked a mental health crisis. Cayo Santiago island, home to a population of rhesus macaques (Macaca mulatta), was devastated by the same storm. We compared social networks of two groups of macaques before and after the hurricane and found an increase in affiliative social connections, driven largely by monkeys most socially isolated before Hurricane Maria. Further analysis revealed monkeys invested in building new relationships rather than strengthening existing ones. Social adaptations to environmental instability might predispose rhesus macaques to success in rapidly changing anthropogenic environments.National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Science Foundation (NSF)The Royal SocietyNational Center for Research Resources (NCRR) and the Office of Research Infrastructure Programs (ORIP) of the National Institutes of HealthBruce McEwen Career Development Fellowship and the Animal Models for the Social Dimensions of Health and Aging Research Networ

Withdrawal rates as a consequence of disclosure of risk associated with manipulation of the cervical spine

<p>Abstract</p> <p>Background</p> <p>The risk associated with cervical manipulation is controversial. Research in this area is widely variable but as yet the risk is not easily quantifiable. This presents a problem when informing the patient of risks when seeking consent and information may be withheld due to the fear of patient withdrawal from care. As yet, there is a lack of research into the frequency of risk disclosure and consequent withdrawal from manipulative treatment as a result. This study seeks to investigate the reality of this and to obtain insight into the attitudes of chiropractors towards informed consent and disclosure.</p> <p>Methods</p> <p>Questionnaires were posted to 200 UK chiropractors randomly selected from the register of the General Chiropractic Council.</p> <p>Results</p> <p>A response rate of 46% (n = 92) was achieved. Thirty-three per cent (n = 30) respondents were female and the mean number of years in practice was 10. Eighty-eight per cent considered explanation of the risks associated with any recommended treatment important when obtaining informed consent. However, only 45% indicated they always discuss this with patients in need of cervical manipulation. When asked whether they believed discussing the possibility of a serious adverse reaction to cervical manipulation could increase patient anxiety to the extent there was a strong possibility the patient would refuse treatment, 46% said they believed this could happen. Nonetheless, 80% said they believed they had a moral/ethical obligation to disclose risk associated with cervical manipulation despite these concerns. The estimated number of withdrawals throughout respondents' time in practice was estimated at 1 patient withdrawal for every 2 years in practice.</p> <p>Conclusion</p> <p>The withdrawal rate from cervical manipulation as a direct consequence of the disclosure of associated serious risks appears unfounded. However, notwithstanding legal obligations, reluctance to disclose risk due to fear of increasing patient anxiety still remains, despite acknowledgement of moral and ethical responsibility.</p

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$reference year 2014). Results: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplaseonly group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. c Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Peer reviewe

Endovascular thrombectomy for ischemic stroke increases disability-free survival, quality of life, and life expectancy and reduces cost

Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$reference year 2014). Results: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00–0.91) in the alteplase-only versus 0.91 (0.65–1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2–8.7) versus 8.9 (4.7–13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2–13.1) versus 4.9 (0.3–8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3–11) days versus 8 (5–14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0–28) versus 27 (0–65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Bruce C. V. Campbell, Peter J. Mitchell, Leonid Churilov, Mahsa Keshtkaran, Keun-Sik Hong, Timothy J. Kleinig … et al. on behalf of the EXTEND-IA Investigator

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras