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Risk Analysis : An Official Publication... Jun 2024This article presents a risk analysis of large language models (LLMs), a type of "generative" artificial intelligence (AI) system that produces text, commonly in...
This article presents a risk analysis of large language models (LLMs), a type of "generative" artificial intelligence (AI) system that produces text, commonly in response to textual inputs from human users. The article is specifically focused on the risk of LLMs causing an extreme catastrophe in which they do something akin to taking over the world and killing everyone. The possibility of LLM takeover catastrophe has been a major point of public discussion since the recent release of remarkably capable LLMs such as ChatGPT and GPT-4. This arguably marks the first time when actual AI systems (and not hypothetical future systems) have sparked concern about takeover catastrophe. The article's analysis compares (A) characteristics of AI systems that may be needed for takeover, as identified in prior theoretical literature on AI takeover risk, with (B) characteristics observed in current LLMs. This comparison reveals that the capabilities of current LLMs appear to fall well short of what may be needed for takeover catastrophe. Future LLMs may be similarly incapable due to fundamental limitations of deep learning algorithms. However, divided expert opinion on deep learning and surprise capabilities found in current LLMs suggests some risk of takeover catastrophe from future LLMs. LLM governance should monitor for changes in takeover characteristics and be prepared to proceed more aggressively if warning signs emerge. Unless and until such signs emerge, more aggressive governance measures may be unwarranted.
PubMed: 38945529
DOI: 10.1111/risa.14353 -
Journal of Gynecologic Oncology Jun 2024Cancer-field surgery by peritoneal mesometrial resection and targeted compartmental lymphadenectomy (PMMR+TCL) for the treatment of endometrial cancer (EC) aims at...
OBJECTIVE
Cancer-field surgery by peritoneal mesometrial resection and targeted compartmental lymphadenectomy (PMMR+TCL) for the treatment of endometrial cancer (EC) aims at optimal locoregional tumor control without the need for adjuvant radiotherapy. In a previous publication we could demonstrate the feasibility of the method and presented encouraging first oncologic data.
METHODS
Following up our 2021 publication, we present data on the treatment of EC by PMMR+TCL in much larger cohort and with longer follow-up.
RESULTS
One hundred and thirty-five patients with EC International Federation of Gynecology and Obstetrics (FIGO) I-IV (75.6% FIGO I) underwent cancer field surgery via PMMR+TCL for EC in the years 2016-2023. Mean follow-up in our cohort was 27.5 months (0, 83; 19.7). The procedure was feasible and safe with favorable intra-and postoperative complication rates. Even though 50.4% of patients had an indication for postoperative radiotherapy following national and international guidelines, the rate of postoperative irradiation administered was 10.4%. The overall recurrence rate was 8.1% and we observed 2 (1.5%) isolated locoregional recurrences.
CONCLUSION
Our results confirm the feasibility and safety of PMMR+TCL in EC patients. Oncologic data are very encouraging and hint at a superior locoregional control without adjuvant irradiation. Larger studies with longer follow-up will be needed to confirm these results.
PubMed: 38945527
DOI: 10.3802/jgo.2025.36.e13 -
Environmental Research Jun 2024Public health is greatly affected by heatwaves, especially as a result of climate change. It is unclear whether heatwaves affect injury hospitalization, especially as...
BACKGROUND
Public health is greatly affected by heatwaves, especially as a result of climate change. It is unclear whether heatwaves affect injury hospitalization, especially as developing countries facing the impact of climate change.
OBJECTIVES
To assess the impact of heatwaves on injury-related hospitalization and the economic burden.
METHODS
The daily hospitalizations and meteorological data from 2014 to 2019 were collected from 23 study sites in 11 meteorological geographic zones in China. We conducted a two-stage time series analysis based on a time-stratified case-crossover design, combined with DLNM to assess the association between heatwaves and daily injury hospitalization, and to further assess the regional and national economic losses resulting from hospitalization by calculating excess hospitalization costs (direct economic losses) and labor losses (indirect economic losses). To determine the vulnerable groups and areas, we also carried out stratified analyses by age, sex, and region.
RESULTS
We found that 6.542% (95%CI: 3.939%, 9.008 %) of injury hospitalization were attributable to heatwaves during warm season (May to September) from 2014-2019. Approximately 361,447 injury hospitalizations were attributed to heatwaves each year in China, leading to an excess economic loss of 5.173 (95%CI: 3.104, 7.196) billion CNY, of which 3.114 (95%CI: 1.454, 4.720) billion CNY for males and 4.785 (95%CI: 3.203, 6.321) billion CNY for people aged 15-64 years. The attributable fraction (AF) of injury hospitalizations due to heatwaves was the highest in the plateau mountain climate zone, followed by the subtropical monsoon climate zone and the temperate monsoon climate zone.
CONCLUSIONS
Heatwaves significantly increase the disease and economic burden of injury hospitalizations, and vary across populations and regions. Our findings implicate the necessity for targeted measures, including raising public awareness, improving healthcare infrastructure, and developing climate resilience policies, to reduce the threat of heatwaves to vulnerable populations and the associated disease and economic burden.
PubMed: 38945512
DOI: 10.1016/j.envres.2024.119509 -
Environmental Research Jun 2024This study aimed to quantify risk of hospitalisations for kidney diseases related to ambient temperature in Central Australia, Northern Territory (NT). Daily...
This study aimed to quantify risk of hospitalisations for kidney diseases related to ambient temperature in Central Australia, Northern Territory (NT). Daily hospitalisation data were extracted for Alice Springs Hospital, Central Australia, 2010 - 2021. The association between daily mean temperature and daily hospital admissions for total kidney and specific kidney conditions was assessed using a quasi-Poisson Generalized Linear Model combined with a distributed lag non-linear model. A total of 52,057 hospitalisations associated with kidney diseases were recorded. In general, risk of specific kidney related hospitalisations was immediate due to hot temperatures and prolonged due to cold temperatures. Relative to the minimum-risk temperature (5.1°C), at 31°C, cumulative relative risk (RR) of hospitalisations for total kidney disease (TKD) was 1.297 [95% CI 1.164,1.446] over lag0-1 days, for chronic kidney disease (CKD) cumulative RR was 1.269 [95% CI 1.115,1.444] and for kidney failure (KF) cumulative RR was 1.252 [95% CI 1.107,1.416] at lag 0, and for urinary tract infection (UTI) cumulative RR was 1.522 [95% CI 1.072,2.162] over lag0-7 days. At 16°C and over lag0-7 days, cumulative RR of hospitalisations for TKD was 1.320 [95% CI 1.135,1.535], for CKD was 1.232 [95% CI 1.025,1.482], for RF was 1.233 [95% CI 1.035,1.470] and for UTI was 1.597 [95% CI 1.143, 2.231]. Both cold and hot temperatures were also associated with increased risks of kidney related total hospitalisations among First Nations Australians and women. Overall, temperature attributable to 13.7% (i.e. 7,138 cases) of kidney related hospitalisations with higher attributable hospitalisations from cold temperature. Given the significant burden of kidney disease and projected increases in extreme temperatures associated with climate change in NT including Central Australia there is a need to implement public health and environmental health risk reduction strategies and awareness programs to mitigate potential adverse health effects of extreme temperatures.
PubMed: 38945510
DOI: 10.1016/j.envres.2024.119502 -
Antiviral Research Jun 2024The WHO declared the official end of the SARS-CoV-2 caused public health emergency on May 5, 2023, after two years in which the virus infected approximately 750 Mio...
The WHO declared the official end of the SARS-CoV-2 caused public health emergency on May 5, 2023, after two years in which the virus infected approximately 750 Mio individuals causing estimated up to 7 Mio deaths. Likely, the virus will continue to evolve in the human population as a seasonal respiratory pathogen. To now prevent severe infection outcomes in vulnerable individuals, effective antivirals are urgently needed to complement the protection provided by vaccines. SARS-CoV-2 enters its host cell via ACE2 mediated membrane fusion, either at the plasma membrane, if the protease TMPRSS2 is present or via the endosome, in a cathepsin dependent fashion. A small number of positive regulators of viral uptake were described in the literature, which are potentially useful targets for host directed antiviral therapy or biomarkers indicating increased or diminished susceptibility to infection. We identified here by cell surface proximity ligation novel proteins, required for efficient virion uptake. Importantly, chemical inhibition of one of these factors, SLC3A2, resulted in robust reduction of viral replication, to that achieved with a TMPRSS2 inhibitor. Our screen identified new host dependency factors for SARS-CoV-2 entry, which could be targeted by novel antiviral therapies.
PubMed: 38945485
DOI: 10.1016/j.antiviral.2024.105951 -
F&S Science Jun 2024The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of Defense, or the United States...
The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of Defense, or the United States Government. This symposium was supported by Sumitomo Pharma. However, the authors received no support for the creation of this manuscript, and the manuscript was created, revised and submitted solely by the authors recognized above.
PubMed: 38945479
DOI: 10.1016/j.xfss.2024.06.006 -
Journal of Theoretical Biology Jun 2024Across early childhood development, sleep behavior transitions from a biphasic pattern (a daytime nap and nighttime sleep) to a monophasic pattern (only nighttime...
Across early childhood development, sleep behavior transitions from a biphasic pattern (a daytime nap and nighttime sleep) to a monophasic pattern (only nighttime sleep). The transition to consolidated nighttime sleep, which occurs in most children between 2- and 5-years-old, is a major developmental milestone and reflects interactions between the developing homeostatic sleep drive and circadian system. Using a physiologically-based mathematical model of the sleep-wake regulatory network constrained by observational and experimental data from preschool-aged participants, we analyze how developmentally-mediated changes in the homeostatic sleep drive may contribute to the transition from napping to non-napping sleep patterns. We establish baseline behavior by identifying parameter sets that model typical 2-year-old napping behavior and 5-year-old non-napping behavior. Then we vary six model parameters associated with the dynamics of and sensitivity to the homeostatic sleep drive between the 2-year-old and 5-year-old parameter values to induce the transition from biphasic to monophasic sleep. We analyze the individual contributions of these parameters to sleep patterning by independently varying their age-dependent developmental trajectories. Parameters vary according to distinct evolution curves and produce bifurcation sequences representing various ages of transition onset, transition durations, and transitional sleep patterns. Finally, we consider the ability of napping and non-napping light schedules to reinforce napping or promote a transition to consolidated sleep, respectively. These modeling results provide insight into the role of the homeostatic sleep drive in promoting interindividual variability in developmentally-mediated transitions in sleep behavior and lay foundations for the identification of light- or behavior-based interventions that promote healthy sleep consolidation in early childhood.
PubMed: 38945471
DOI: 10.1016/j.jtbi.2024.111892 -
Journal of Pain and Symptom Management Jun 2024Outpatient palliative care (PC) has strong evidence demonstrating impact across serious illnesses, resulting in growing demand for skilled outpatient PC clinicians....
CONTEXT
Outpatient palliative care (PC) has strong evidence demonstrating impact across serious illnesses, resulting in growing demand for skilled outpatient PC clinicians. However, there is limited literature examining the existing state and quality of outpatient PC education during post-graduate training.
OBJECTIVES
Characterize the current state of outpatient training in United States (US) Hospice and Palliative Medicine (HPM) physician fellowships and elicit perceptions regarding quality of outpatient PC education.
METHODS
A cross-sectional survey of US adult HPM fellowship program directors (PDs) or their designee conducted between March-July 2023.
RESULTS
Of 161 programs, 85 participated (53% response rate) with representation across all US regions. HPM fellows spend a median of 4.8 weeks in outpatient PC compared to 24 weeks inpatient PC and 10.5 weeks in hospice settings. Over half (51%) of fellows saw outpatients from primarily one disease type with limited exposure to patients with other serious illnesses. Across programs, fellows' clinic structure, interdisciplinary team composition, and didactic experiences varied. On a 5-point rating scale, PDs reported significantly lower quality outpatient versus inpatient training (mean rating: 3.58 vs. 4.62, p< 0.001) and perceived fellows as less prepared for independent outpatient practice upon graduation (mean: 4.06 vs. 4.73, p< 0.001).
CONCLUSION
Our survey of US HPM fellowships identified multiple gaps between outpatient and inpatient PC education and training during fellowship and raises concern about the adequacy of outpatient PC training. To prepare the HPM workforce to meet the diverse needs of seriously ill populations and ensure adequate access, outpatient PC training requires reform.
PubMed: 38945458
DOI: 10.1016/j.jpainsymman.2024.06.017 -
The Journal of Biological Chemistry Jun 2024Opioid use disorders (OUD) and overdoses are ever-evolving public health threats that continue to grow in incidence and prevalence in the United States and abroad....
Opioid use disorders (OUD) and overdoses are ever-evolving public health threats that continue to grow in incidence and prevalence in the United States and abroad. Current treatments consist of opioid receptor agonists and antagonists, which are safe and effective but still suffer from some limitations. Murine and humanized monoclonal antibodies (mAb) have emerged as an alternative and complementary strategy to reverse and prevent opioid-induced respiratory depression. To explore antibody applications beyond traditional heavy-light chain mAbs, we identified and biophysically characterized a novel single-domain antibody specific for fentanyl from a camelid variable-heavy-heavy (VHH) domain phage display library. Structural data suggested that VHH binding to fentanyl was facilitated by a unique domain-swapped dimerization mechanism, which accompanied a rearrangement of complementarity-determining region (CDR) loops leading to the formation of a fentanyl-binding pocket. Structure-guided mutagenesis further identified an amino acid substitution that improved the affinity and relaxed the requirement for dimerization of the VHH in fentanyl binding. Our studies demonstrate VHH engagement of an opioid and inform on how to further engineer a VHH for enhanced stability and efficacy, laying the groundwork for exploring the in vivo applications of VHH-based biologics against OUD and overdose.
PubMed: 38945452
DOI: 10.1016/j.jbc.2024.107502 -
The Journal of Pediatrics Jun 2024To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB).
OBJECTIVE
To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB).
STUDY DESIGN
From a cohort of prospectively enrolled infants born preterm (N=92), plasma samples of very preterm (VPT; GA, 28+0 to 31+6 weeks, N =27) and moderate/late preterm (M/LPT; GA, 32+0 to 35+6 weeks, N =33) infants requiring phototherapy for NHB were collected prior to the initiation of phototherapy and 24 hours after starting phototherapy. An additional sample was collected 48 hours after starting phototherapy in a randomly selected subset (N=30; VPT N=15; M/LPT N=15). Metabolite profiles were determined using ultraperformance liquid chromatography tandem mass spectroscopy. Two-way ANCOVA was used to identify metabolites that differed between GA groups and timepoints after adjusting for total serum bilirubin (TSB) levels (FDR q-value<0.05). Top impacted pathways were identified using pathway over-representation analysis.
RESULTS
Phototherapy was initiated at lower TSB (mean ± SD mg/dL) levels in VPT compared with M/LPT infants (7.3 ± 1.4 vs. 9.9 ± 1.9, p<0.01). We identified 664 metabolites that were significant for a phototherapy effect, 191 metabolites significant for GA, and 46 metabolites significant for GA x phototherapy interaction (FDR q-value<0.05). Longer duration phototherapy had a larger mean effect size (24 hours post-phototherapy: d=0.36; 48 hours post-phototherapy: d=0.43). Top pathways affected by phototherapy included membrane lipid metabolism, one-carbon metabolism, creatine biosynthesis, and oligodendrocyte differentiation.
CONCLUSION
Phototherapy alters the plasma metabolite profile more than GA in preterm infants with NHB, affecting pathways related to lipid and one-carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation.
PubMed: 38945444
DOI: 10.1016/j.jpeds.2024.114175