A Proposal for Finite But Unbounded Human Lifetimes

Close analysis of an extensive data set combined with independent evidence prompts our proposal to view human lifetimes as individually finite but collectively unbounded. We formulate a model incorporating this idea whose predictions agree very well with the observed data. In the model, human lifetimes are theoretically unbounded, but the probability of an individual living to an extreme age is negligible, so lifetimes are effectively limited. Our model incorporates a mortality hazard rate plateau and a late-life mortality deceleration effect in conjunction with a newly observed advanced age mortality acceleration. This reconciles many previously observed effects. The model is temporally stable: consistent with observation, parameters do not change over time. As an application, assuming no major medical advances, we predict the emergence of many individuals living past 120, but due to accelerating mortality find it unlikely that any will subsequently survive to an age of 125.

Early-Middle Ordovician cephalopods from Ny Friesland, Spitsbergen – a pelagic fauna with Laurentian affinities

The collection of cephalopods from eight sampling horizons within the Olenidsletta Member, Valhallfonna Formation, Floian–Dapingian, from Profilstranda and nearby Profilbekken, Ny Friesland, Spitsbergen, resulted in the detection of 31 species, 20 genera, and 12 families from the Ellesmerocerida, Endocerida, Riocerida, Dissidocerida, Orthocerida, Tarphycerida, and Oncocerida. Of these, five genera (Ethanoceras gen. nov., Hinlopoceras gen. nov., Nyfrieslandoceras gen. nov., Olenidslettoceras gen. nov., Svalbardoceras gen. nov.) and 19 species (Bactroceras fluvii sp. nov., Buttsoceras buldrebreenense sp. nov., Cycloplectoceras hinlopense sp. nov., Cyclostomiceras profilstrandense sp. nov., Deltoceras beluga sp. nov., Eosomichelinoceras borealis sp. nov., Ethanoceras solitudines gen. et sp. nov., Hemichoanella occulta sp. nov., Hinlopoceras tempestatis gen. et sp. nov., H. venti gen. et sp. nov., Lawrenceoceras ebenus sp. nov., L. larus sp. nov., Litoceras profilbekkenense sp. nov., Nyfrieslandoceras bassleroceroides gen. et sp. nov., Olenidslettoceras farmi gen. et sp. nov., Protocycloceras minor sp. nov., Proterocameroceras valhallfonnense sp. nov., Svalbardoceras sterna gen. et sp. nov., S. skua gen. et sp. nov.) are new. The diagnoses of the Cyptendoceratidae, Bactroceratidae and of Deltoceras Hyatt, 1894 are emended. Well preserved early growth stages in several species are remarkable. Turnover between the sampling horizons and between sampling intervals is high. The differences in composition, diversity and evenness of the assemblages are interpreted as reflecting changing depth and oxygenation depositional bottom conditions. The co-occurrence of endemic and cosmopolitan species is interpreted as resulting from a high vertical niche differentiation and from eustatically generated lateral shifts of facies zones. Based on calculations of phragmocone implosion depths, depositional depths of 50–130 m are plausible for the Olenidsletta Member, supporting independent evidence from biomarker signatures. Several cephalopod species of the Olenidsletta Member represent odd mosaics of morphological features of previously known cephalopods which cannot be unambiguously assigned to one of the existing cephalopod higher taxa. Results from a cladistic analysis shed new light on the early evolution of the Oncocerida and Orthocerida.

The medieval castle of Dun Aros

An investigation of Aros Castle (NM 56287 44989) was undertaken which included low-level survey of the site’s north-west block followed by lab-based analysis of a mixed assemblage of building material samples. The study presents the first independent evidence relating to the chronology of building construction on the site and reveals the wide range of techniques and materials exploited during that process. The results are consistent with surviving documentary, architectural and art-historical evidence, and highlight the importance of the site’s masonry structures for the mediation and display of Clan Donald power during their later medieval floruit as Lords of the Isles and Earls of Ross. View supplementary material here.

An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression

Research over the last two decades has established ketamine as a safe, effective, fast-acting, and sustained antidepressant that significantly reduces adverse symptoms associated with depression, even in patients who are treatment resistant. Much of this research has evolved within the framework of several independent branches of scientific inquiry: in addition to the study of ketamine is a non-selective NMDAR antagonist with rapid antidepressant effects, it has also been found effective as a psychoplastogen that stimulates synaptogenesis and increases neuroplasticity, as a powerful anti-inflammatory that may improve inflammation-related depressive symptoms, as a substance that induces beneficial high entropy brain states, and as a subjectively impactful psychedelic agent. Each branch of inquiry has generated independent evidence of ketamine's efficacy but has advanced without substantive coordination or communication with other lines of inquiry. Integrative research that considers these branches of research together may lead toward a better understanding of ketamine's effects and improved treatment protocols and clinical outcomes. Such an overview can inform more comprehensive patient care through: (a) informed patient psychoeducation that encompasses all of ketamine's mechanisms of action; (b) calibration of optimal dosage to ensure induction and maintenance of high entropy brain states during each ketamine session utilizing EEG measurement; (c) Improved management of emergence side effects through proper care for set and setting; (d) inclusion of pre-selected appropriate music to enhance the emotional experience; (e) increased monitoring of ketamine effects on cortical activity, inter-hemispheric imbalance, and inflammation-related levels of cytokines to further improvements in ketamine protocols; and (f) appropriate timing of any adjunctive psychotherapy sessions to coincide with peak neurogenesis at 24–48 h post ketamine treatment.

The P600, but not N400, is modulated by sustained attention

The functional significance of the two prominent language-related ERP components N400 and P600 is still under debate. It has recently been suggested that one important dimension along which the two vary, is in terms of automaticity versus attentional control, with N400 amplitudes reflecting more automatic and P600 amplitudes reflecting more controlled aspects of sentence comprehension. The availability of executive resources necessary for controlled processes depends on sustained attention, which fluctuates over time. Here, we thus tested whether P600 and N400 amplitudes depend on the level of sustained attention. We re-analyzed EEG and behavioral data from a sentence processing task by Sassenhagen & Bornkessel-Schlesewsky (2015, Cortex), which included sentences with morphosyntactic and semantic violations. Participants read sentences phrase by phrase and indicated whether a sentence contained any type of anomaly as soon as they had the relevant information. To quantify periods of high versus low sustained attention, we extracted a moving reaction time coefficient of variation over the entire course of the task. We found that the P600 amplitude was significantly larger during periods of low reaction time variability (high sustained attention) than in periods of high reaction time variability (low sustained attention). In contrast, the amplitude of the N400 was not affected by reaction time variability. These results thus suggest that the P600 component is sensitive to sustained attention while the N400 component is not, which provides independent evidence for accounts suggesting that P600 amplitudes reflect more controlled and N400 amplitudes more automatic aspects of sentence comprehension.

Side effects and Immunogenicity following administration of the Sputnik V COVID-19 vaccine in health care workers in Iran

The Sputnik V is a COVID- 19 vaccine developed by the Gamalia institute of epidemiology and microbiology and released on August 11, 2020. We provided independent evidence on side effects and immunogenicity following the administration of the Sputnik V COVID-19 in Iran. In this observational study, the healthcare workers who were vaccinated with the Sputnik V COVID-19 vaccine within February and April 2021 were evaluated. Among a total of 13,435 vaccinated healthcare workers, we received 3236 self-declaration reports of Sputnik V associated adverse events with the mean age 39.32 ± 10.19 years old which 38.8% were men and 61.2% were women. Totally 68.8% of females versus 66.2% of males reported side effects after receiving the first dose and 31.2% of females versus 33.8% of males reported side effects after the second dose of vaccine. The most common side effect was a pain in the injection site (56.9%), fatigue (50.9%), body pain (43.9%), headache (35.7%), fever (32.9%), joint pain (30.3%), chilling (29.8%) and drowsiness (20.3%). Side effects of the vaccine were significantly more frequent in females and younger individuals. Among a total of 238 participants, more than 90% after the first and second dose of vaccine had a detectable level of SARS-CoV-2 RBD antibody and SARS-CoV-2 neutralizing antibody. Although the overall rate of adverse effects was higher than the interim results from randomized controlled trials, our findings support the manufacturer’s reports about the high humoral immunogenicity of vaccine against COVID-19.

A puzzle about narrative progression and causal reasoning

This chapter argues that key to an analysis of narrative progression are aspectual constraints imposed by coherence relations. This argument is based on a discourse like “A cat bit into a mouse while it was wiggling its tail. It was dead”. The fact that it’s infelicitous is remarkable given that the following is fine: “A mouse was dead. A cat bit into it while it was wiggling its tail”. The chapter explains these data in two steps. First, it proposes definitions for the coherence relations, RESULT and EXPLANATION, in which the former, but not the latter, rules out stative arguments. Second, it provides axioms in a default logic which predict the conditions under which these and competing coherence relations are typically inferred. It provides independent evidence for the proposed analysis from discourses involving exclamatives, temporal indexicals, and deverbals. It also considers discourses that challenge the analysis involving perspectival expressions.

A study on adverse events following ChAdOx1 nCoV-19 CovishieldTM vaccination among beneficiaries at tertiary care centre, Hyderabad, India

Background: COVID-19 vaccine in present pandemic situation has been emerged as a blessing in disguise. Studies found to be associated with vaccine side-effects and it is an important factor that influences the confidence of vaccine uptake in general population. Present study was designed to provide an independent evidence on ChAdOx1 nCoV-19 vaccine side effects.Methods: A cross sectional study was conducted between January 2021 and February 2021 at our tertiary care centre among health care workers vaccinated using a validated questionnaire. Study subjects were contacted through phone to know about any adverse events following immunization for 0-24 hours, 24-48 hours and 48-72 hours. Data collected was entered and analysed with MS excel software 2007 and Epi info 3.5.3.Results: Healthcare workers participated were 1364. Majority of the symptoms following immunization were highest in age group of 18-28 years. Reported symptoms were pain at the site of injection- 619 (45.4%), fever- 423 (31%), Body pains- 318 (23.3%), headache- 189 (13.9%), tiredness- 142 (10.4%), swelling at the site of injection- 40 (2.9%), dizziness- 30 (2.2%), redness at the site of injection- 25 (1.8%), joint pains- 23 (1.7%), rash- 06 (0.4%), Breathlessness- 03 (0.2%) respectively.Conclusions: Overall results found the occurrence of side-effects which are in terms of manufacturer’s data and it has been noticed in young age. This study imparts the confidence for taking vaccination and further studies are required to minimize vaccine hesitancy (VH) and strengthen the public to boost their confidence in present vaccination drive.

Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date.

A comparative field evaluation of six medicine quality screening devices in Laos

Background Medicine quality screening devices hold great promise for post-market surveillance (PMS). However, there is little independent evidence on their field utility and usability to inform policy decisions. This pilot study in the Lao PDR tested six devices’ utility and usability in detecting substandard and falsified (SF) medicines. Methodology/principal findings Observational time and motion studies of the inspections by 16 Lao medicine inspectors of 1) the stock of an Evaluation Pharmacy (EP), constructed to resemble a Lao pharmacy, and 2) a sample set of medicines (SSM); were conducted without and with six devices: four handheld spectrometers (two near infrared: MicroPHAZIR RX, NIR-S-G1 & two Raman: Progeny, Truscan RM); one portable mid-infrared spectrometer (4500a), and single-use paper analytical devices (PAD). User experiences were documented by interviews and focus group discussions. Significantly more samples were wrongly categorised as pass/fail with the PAD compared to the other devices in EP inspections (p<0.05). The numbers of samples wrongly classified in EP inspections were significantly lower than in initial visual inspections without devices for 3/6 devices (NIR-S-G1, MicroPHAZIR RX, 4500a). The NIR-S-G1 had the fastest testing time per sample (median 93.5 sec, p<0.001). The time spent on EP visual inspection was significantly shorter when using a device than for inspections without devices, except with the 4500a, risking missing visual clues of samples being SF. The main user errors were the selection of wrong spectrometer reference libraries and wrong user interpretation of PAD results. Limitations included repeated inspections of the EP by the same inspectors with different devices and the small sample size of SF medicines. Conclusions/significance This pilot study suggests policy makers wishing to implement portable screening devices in PMS should be aware that overconfidence in devices may cause harm by reducing inspectors’ investment in visual inspection. It also provides insight into the advantages/limitations of diverse screening devices in the hands of end-users.