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The large complex of archeological and paleontological sites of Melka Kunture is located about 50 km SSW of Addis Ababa (base camp coordinates 8.708° N, 38.594° E), on the banks of the Upper Awash in the Ethiopian plateau at elevations of 2000–2200 m a.s.l. (Figure 21.1); it includes numerous archeological sites that yield tens of thousands of artifacts. It has no equivalent in East Africa in documenting the full evolutionary sequence of lithic industries, from the late Oldowan to historic times, on the Ethiopian Highlands. It is also unique in providing abundant faunal remains that help reconstruct the diet of early hominins and, together with rich floral spectra, their environment at high altitudes.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Little is known about respiratory viruses infection in Guinea. Influenza surveillance has not been implemented in Guinea mainly because of the paucity of laboratory infrastructure and capacity. This paper presents the first influenza surveillance data in Guinea.
Swabs were obtained from August 2018 through December 2019 at influenza sentinel sites and transported to the Institut National de Santé Publique for testing. Ribonucleic acid was extracted and tested for the presence of influenza A and B by real-time reverse transcription-polymerase chain reaction (RT-PCR). Positive samples were further characterised to determine the subtypes and lineages of influenza viruses.
A total of 862 swabs were collected and tested. Twenty-three per cent of samples tested positive for influenza A and B viruses. Characterisation of positive specimens identified influenza A/H1N1pmd09 (2.5%), influenza A/H3N2 (57.3%), influenza B/Victoria lineage (36.7%) and 7 (3.5%) influenza B with undetermined lineage. Influenza B virus activity clustered in August through November while influenza A/H3N2 displayed two clusters of activities that appeared in May through August and November through December.
For the first time in Guinea, the epidemiology, diversity and period of circulation of influenza viruses were studied. The results indicate the predominance and the periods of activities of influenza B Victoria lineage and influenza A/H3N2 which are important information for preventive strategies. It is warranted to extend the influenza surveillance to other parts of Guinea to better understand the epidemiology of the viruses and monitor the emergence of influenza strains with pandemic potential.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT.
Methods:
Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0–3 or equal to pre-stroke mRS at 3 months.
Results:
Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36–0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83–0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32–10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08–0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization.
Conclusions:
Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.
This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.
Visible to short-wave infrared (VSWIR, 0.4–5.0 µm) reflectance spectroscopy is a powerful tool to identify and map mineral groups on the martian surface. The Mars Express/OMEGA and Mars Reconnaissance Orbiter/CRISM instruments have characterized more than 30 mineral groups, revolutionizing previous understanding of martian crustal composition and the role of water in altering it. Analyses of these spectral images revealed the primary structure of the crust to be dominated by basalt, over a deep layer of segregated pyroxene- and olivine-rich plutons, with sparse feldspar-rich, differentiated intrusions. Martian volatile-bearing environments have evolved through four phases: the pre-Noachian to early Noachian period when alteration by liquid water occurred near the surface and deep in the subsurface, in chemically neutral to alkaline environments that formed hydrous silicates and carbonates; the middle to late Noachian period when liquid water was widely present at the surface forming valley networks, lacustrine deposits, and clay-rich pedogenic horizons; the early Hesperian to early Amazonian period during which water became increasingly acidic and saline, forming deposits rich in sulfate salts, chlorides, and hydrated silica; and the Amazonian period when surface water has existed predominantly as ice, with only localized reaction with regolith and briny flow on the surface.
Simulation plays an integral role in the Canadian healthcare system with applications in quality improvement, systems development, and medical education. High-quality, simulation-based research will ensure its effective use. This study sought to summarize simulation-based research activity and its facilitators and barriers, as well as establish priorities for simulation-based research in Canadian emergency medicine (EM).
Methods
Simulation-leads from Canadian departments or divisions of EM associated with a general FRCP-EM training program surveyed and documented active EM simulation-based research at their institutions and identified the perceived facilitators and barriers. Priorities for simulation-based research were generated by simulation-leads via a second survey; these were grouped into themes and finally endorsed by consensus during an in-person meeting of simulation leads. Priority themes were also reviewed by senior simulation educators.
Results
Twenty simulation-leads representing all 14 invited institutions participated in the study between February and May, 2018. Sixty-two active, simulation-based research projects were identified (median per institution = 4.5, IQR 4), as well as six common facilitators and five barriers. Forty-nine priorities for simulation-based research were reported and summarized into eight themes: simulation in competency-based medical education, simulation for inter-professional learning, simulation for summative assessment, simulation for continuing professional development, national curricular development, best practices in simulation-based education, simulation-based education outcomes, and simulation as an investigative methodology.
Conclusion
This study summarized simulation-based research activity in EM in Canada, identified its perceived facilitators and barriers, and built national consensus on priority research themes. This represents the first step in the development of a simulation-based research agenda specific to Canadian EM.
We study the behavior of the game operator $$ on Wadge classes of Borel sets. In particular we prove that the classical Moschovakis results still hold in this setting. We also characterize Wadge classes ${\bf{\Gamma }}$ for which the class has the substitution property. An effective variation of these results shows that for all $1 \le \eta < \omega _1^{{\rm{CK}}}$ and $2 \le \xi < \omega _1^{{\rm{CK}}}$, is a Spector class while is not.
Most endovascular innovations have been introduced into clinical care by showing good outcomes in small enthusiastic case series of selected patients. Randomized clinical trials (RCTs) have rarely been performed, except for acute ischemic stroke, but even then most trial designs were too explanatory to inform clinical decisions. In this article, we review 2 × 2 tables and forest plots that summarize RCT results to examine methodological issues in the design and interpretation of clinical studies. Research results can apply in practice when RCTs are all-inclusive, pragmatic trials. Common problems include the following: (i) using restrictive eligibility criteria in explanatory trials, instead of including the diversity of patients in need of care, which hampers future generalizability of results; (ii) ignoring an entire line of the 2 × 2 table and excluding patients who do not meet the proposed criteria of a diagnostic test in its evaluation (perfusion studies) which renders clinical inferences misleading; (iii) ignoring an entire column of the 2 × 2 table and comparing different patients treated using the same treatment instead of different treatments in the same patients (the “wrong axis” comparisons of prognostic studies and clinical experience) which leads to unjustified treatment decisions and actions; or (iv) combining all aforementioned problems (case series and epidemiological studies). The most efficient and reliable way to improve patient outcomes, after as well as long before research results are available, is to change the way we practice: to use care trials to guide care in the presence of uncertainty.
We have combined global magnetohydrodynamic (MHD) simulations of the solar wind and magnetosphere interaction with an implicit particle-in-cell simulation (PIC) and used this approach to model magnetic reconnection at both the dayside magnetopause and in the magnetotail plasma sheet. In this approach, we first model the magnetospheric configuration driven by the solar wind using the MHD simulation. At a time of interest (usually when a thin current sheet has formed in the MHD simulation), we load a large particle-in-cell simulation with plasma and fields based on the MHD state. We use the MHD results to set the boundary conditions on the PIC simulation. The coupling between the two models is one way – the PIC results do not change the MHD results. In these calculations, we use the UCLA global MHD code and the iPic3D implicit particle-in-cell code. In this paper we describe this technique in detail. As an example of this approach, we present PIC results on reconnection in the magnetotail during a magnetospheric substorm.
Neuroendovascular and neurointerventional therapy is a specialty where disseminating personal knowledge and expert opinion is extremely important, owing to the lack of large-scale clinical trials. The management of complications that occur during or immediately after therapeutic interventions is particularly challenging because these can significantly affect patient outcomes. This book presents how various complication scenarios are handled by well-qualified authorities in the field of neurointervention from three disciplines: neurology, neurosurgery, and neuroradiology. Contributors describe their management of these complications, focusing on the common principles that all the specialists agree on, and give tips and tricks for 'bailout' procedures to help get the practitioner out of trouble. The book is well illustrated and covers the full range of neuroendovascular and neurointerventional procedures. The book will appeal to neurointerventionists, neuroradiologists, stroke physicians, neurosurgeons and vascular surgeons for its practical approach to managing these commonly encountered problems.
This paper is an overview of the transition process for students with disability who are exiting from high school programs into adult life in the United States. Information about available adult services and the changing nature of the employment situation is highlighted. Further, practices that are currently considered to be the best by those actively involved in conducting research and articulating models for improving the future for persons with disability are briefly described. Finally issues and barriers that prevent persons with disability from establishing an adult presence through full participation within our communities are discussed and recommendations about service provision offered.