Teknologi Litik di Situs Talimbue, Sulawesi Tenggara: Teknologi Berlanjut dari Masa Pleistosen Akhir Hingga Holosen.

Abstract.  The  Lithic  Technology  at  Talimbue  Site,  Southeast  Sulawesi:  Continuing  Technology from Late Pleistocene up to Holocene Periods. The Talimbue site at Southeast Sulawesi is packed with  lithic  and  these  offer  a  new  perspective  on  the  lithic  technology  of  Sulawesi.  The  absence  of information  on  the  prehistoric  lithic  technology  of  Southeast  Sulawesi  is  a  factor  of  interest  that makes  research  on  knowledge  of  the  Talimbue  site  necessary.  Lithic  artefacts  were  manufactured from  the  terminal  Pleistocene  to  the  Late  Holocene.  This  research  will  disentangle  the  details  of the lithic technology at the Talimbue Site. The analyzed flaked stone artefacts fall into 3 categories, which are retouched flakes, debitage and cores. For its part, debitage was classified into 3 categories, which are complete flakes, broken flakes and debris. The retouch index was also measured so as to provide a quantitative estimate of the level of retouch intensity of the retouched flakes. The results of  the  analysis  indicate  changes  in  the  stone  flake  technology  during  the  period  of  occupation  of the Talimbue Site. The change of technology occurs because the process of adaptation caused by a change of environment. Abstrak. Temuan  litik  yang  sangat  padat  di  Situs  Talimbue  di  Sulawesi  Tenggara  menunjukkan sebuah persepektif baru dalam kajian teknologi litik di Sulawesi. Kekosongan informasi teknologi litik masa prasejarah di wilayah Sulawesi Tenggara adalah hal yang menarik dikaji dalam penelitian di Situs Talimbue. Artefak litik digunakan dari masa Pleistosen Akhir hingga masa Holosen Akhir. Penelitian ini akan menguraikan secara detail bagaimana teknologi litik di Situs Talimbue. Artefak batu diserpih yang dianalisis menjadi 3 kategori, yaitu serpih diretus, serpihan dan batu inti. Serpihan kemudian  diklasifikasi  menjadi  3  kategori,  yaitu  serpih  utuh,  serpih  rusak  dan  tatal.  Pengukuran indeks retus juga dilakukan bertujuan untuk mengestimasi secara kuantitatif tingkat intensitas retus terhadap serpih yang telah diretus. Hasil penelitian menunjukkan perubahan teknologi artefak batu diserpih terjadi selama masa hunian di Situs Talimbue. Perubahan teknologi terjadi karena adanya proses adaptasi yang disebabkan oleh perubahan lingkungan

Metal-Age maritime culture at Jareng Bori rockshelter, Pantar Island, eastern Indonesia

The archaeological record of Wallacea remains exceptionally fragmentary. This is especially the case for late Holocene human occupation of the region when lifestyle and culture in marginal island environments is relatively unknown. Here we report on the archaeology of Jareng Bori rockshelter, a Metal-Age site spanning c. 1800 cal. BP up to the late historic period and situated on the eastern coast of Pantar Island in the Lesser Sunda Islands of eastern Indonesia. We use osteoarchaeological (human and vertebrate remains), invertebrate zooarchaeological (crustacean and molluscan remains), technological (lithics, shell, and pottery) and chemical sourcing (obsidian and metal) datasets to discuss networking, migration, and human subsistence strategies during this recent period of history. While some communities were no doubt living in open village settlements where they were producing pottery, the data indicate that aspects of maritime life-ways continued much as in earlier Pleistocene settlements, with people using rockshelters like Jareng Bori to pursue a range of subsistence activities focused on the shoreline. Shellfishing of rocky and reef intertidal species and fishing for mostly small herbivorous and omnivorous fishes was practised, while domestic animals only appear in the late historic period. Wider regional cultural interactions and networking are epitomized by obsidian exchange, dental modification practices, and pottery decorations, while lithic analyses indicates continuity of stone tool technology up until recent times

Reduced clinical and postmortem measures of cardiac pathology in subjects with advanced Alzheimer's Disease

Background. Epidemiological studies indicate a statistical linkage between atherosclerotic vascular disease (ATH) and Alzheimer\u27s disease (AD). Autopsy studies of cardiac disease in AD have been few and inconclusive. In this report, clinical and gross anatomic measures of cardiac disease were compared in deceased human subjects with and without AD. Methods. Clinically documented cardiovascular conditions from AD (n = 35) and elderly non-demented control subjects (n = 22) were obtained by review of medical records. Coronary artery stenosis and other gross anatomical measures, including heart weight, ventricular wall thickness, valvular circumferences, valvular calcifications and myocardial infarct number and volume were determined at autopsy. Results. Compared to non-demented age-similar control subjects, those with AD had significantly fewer total diagnosed clinical conditions (2.91 vs 4.18), decreased coronary artery stenosis (70.8 vs 74.8%), heart weight (402 vs 489 g for males; 319 vs 412 g for females) and valvular circumferences. Carriage of the Apolipoprotein E-ε4 allele did not influence the degree of coronary stenosis. Group differences in heart weight remained significant after adjustment for age, gender, body mass index and apolipoprotein E genotype while differences in coronary artery stenosis were significantly associated with body mass index alone. Conclusions. The results are in agreement with an emerging understanding that, while midlife risk factors for ATH increase the risk for the later development of AD, once dementia begins, both risk factors and manifest disease diminish, possibly due to progressive weight loss with increasing dementia as well as disease involvement of the brain\u27s vasomotor centers. © 2011 Beach et al; licensee BioMed Central Ltd

The persistence of epiphyseal scars in the distal radius in adult individuals

The use of radiographic imaging in the estimation of chronological age facilitates the analysis of structures not visible on gross morphological inspection. Following the completion of epiphyseal fusion, a thin radio-opaque band, the epiphyseal scar, may be observed at the locus of the former growth plate. The obliteration of this feature has previously been interpreted as the final stage of skeletal maturation and consequently has been included as a criterion in several methods of age estimation, particularly from the distal radius. Due to the recommendations relating to age estimation in living individuals, accurate assessment of age from the distal radius is of great importance in human identification; however, the validity of the interpretation of the obliteration of the epiphyseal scar as an age-related process has not been tested. A study was undertaken to assess the persistence of epiphyseal scars in adults between 20 and 50 years of age through the assessment of 616 radiographs of left and right distal radii from a cross-sectional population. This study found that 86 % of females and 78 % of males retained some remnant of the epiphyseal scar in the distal radius. The relationships between chronological age, biological sex and the persistence of the epiphyseal scar were not statistically significant. The findings of this study indicate that the epiphyseal scars may persist in adult individuals until at least 50 years of age. No maximum age should therefore be applied to the persistence of an epiphyseal scar in the distal radius

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p