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Characterizing Mycobacterium abscessus complex (MABSC) biofilms under host-relevant conditions is essential to the design of informed therapeutic strategies targeted to this persistent, drug-tolerant, population of extracellular bacilli. Using synthetic cystic fibrosis medium (SCFM) which we previously reported to closely mimic the conditions encountered by MABSC in actual cystic fibrosis (CF) sputum and a new model of biofilm formation, we show that MABSC biofilms formed under these conditions are substantially different from previously reported biofilms grown in standard laboratory media in terms of their composition, gene expression profile and stress response. Extracellular DNA (eDNA), mannose-and glucose-containing glycans and phospholipids, rather than proteins and mycolic acids, were revealed as key extracellular matrix (ECM) constituents holding clusters of bacilli together. None of the environmental cues previously reported to impact biofilm development had any significant effect on SCFM-grown biofilms, most likely reflecting the fact that SCFM is a nutrient-rich environment in which MABSC finds a variety of ways of coping with stresses. Finally, molecular determinants were identified that may represent attractive new targets for the development of adjunct therapeutics targeting MABSC biofilms in persons with CF.

A recent study used both qualitative and quantitative methods to examine families' perceptions of service needs for children with disruptive behavior problems. Focusing on the qualitative component of the study, the present paper discusses the modified Nominal Group Technique used in focus groups attended by carers living in rural, regional or metropolitan contexts. Three questions posed to each focus group sought to identify families' concerns about health facilities and/or related support services currently available to them, the benefits they perceived in these services and the changes needed to make these services more appropriate or accessible to them. Major themes in the responses relating to each of these questions included concerns about a lack of, or perceived need for, access to help/support, benefits in schools that accommodated the needs of the children, and support from the community. Families' recommendations for change included increased access to health care advice, information and/or support systems. [ABSTRACT FROM AUTHOR]

The increasing pressure to reduce costs and improve outcomes is driving the health care industry to view information as a competitive advantage. Timely information is required to help reduce inefficiencies and improve patient care. Numerous disparate operational or transactional information systems with inconsistent and often conflicting data are no longer adequate to meet the information needs of integrated care delivery systems and networks in competitive managed care environments. This article reviews decision support system characteristics and describes a process to assess the preparedness of an organization to implement and use decision support systems to achieve a more effective, information-based decision process. Decision support tools included in this article range from reports to data mining. Copyright © 2000 by Aspen Publishers, Inc. [ABSTRACT FROM AUTHOR]

, , 189-194. A method of fixing lungs by inflating them with heated formalin vapour is described. This method facilitates postmortem correlations between radiographic and histological appearances. [ABSTRACT FROM PUBLISHER]

Ribosomes frequently translate truncated or damaged mRNAs due to the extremely short half-life of mRNAs in bacteria. When ribosomes translate mRNA that lacks a stop codon (non-stop mRNA), specialized pathways are required to rescue the ribosome from the 3' end of the mRNA. The most highly conserved non-stop rescue pathway is trans -translation, which is found in greater than 95% of bacterial genomes. In all Proteobacteria that have been studied, the alternative non-stop ribosome rescue factors, ArfA and ArfB, are essential in the absence of trans -translation. Here, we investigate the interaction between non-stop rescue pathways and RqcH, a ribosome quality control factor that is broadly conserved outside of Proteobacteria. RqcH does not act directly on non-stop ribosomes but adds a degron tag to stalled peptides that obstruct the large ribosomal subunit, which allows the stalled peptide to be cleared from the ribosome by peptidyl-tRNA hydrolase (PTH). We show that Bacillus subtilis can survive without trans -translation and BrfA (Bacillus ArfA homolog), due to the presence of RqcH. We also show that expression of RqcH and its helper protein RqcP rescues the synthetic lethality of Δ ssrA Δ arfA in Escherichia coli . These results suggest that non-stop ribosome complexes can be disassembled and then cleared because of the tagging activity of RqcH, and that this process is essential in the absence of non-stop ribosome rescue pathways. Moreover, we surveyed the conservation of ribosome rescue pathways in >14,000 bacterial genomes. Our analysis reveals a broad distribution of non-stop rescue pathways, especially trans -translation and RqcH, and a strong co-occurrence between the ribosome splitting factor MutS2 and RqcH. Altogether, our results support a role for RqcH in non-stop ribosome rescue and provide a broad survey of ribosome rescue pathways in diverse bacterial species.

Soqotra, an island situated at the mouth of the Gulf of Aden in the northwest Indian Ocean between Africa and Arabia, is home to ~60,000 people subsisting through fishing and semi-nomadic pastoralism who speak a Modern South Arabian language. Most of what is known about Soqotri history derives from writings of foreign travellers who provided little detail about local people, and the geographic origins and genetic affinities of early Soqotri people has not yet been investigated directly. Here we report genome-wide data from 39 individuals who lived between ~650 and 1750 CE at six locations across the island and document strong genetic connections between Soqotra and the similarly isolated Hadramawt region of coastal South Arabia that likely reflects a source for the peopling of Soqotra. Medieval Soqotri can be modelled as deriving ~86% of their ancestry from a population such as that found in the Hadramawt today, with the remaining ~14% best proxied by an Iranian-related source with up to 2% ancestry from the Indian sub-continent, possibly reflecting genetic exchanges that occurred along with archaeologically documented trade from these regions. In contrast to all other genotyped populations of the Arabian Peninsula, genome-level analysis of the medieval Soqotri is consistent with no sub-Saharan African admixture dating to the Holocene. The deep ancestry of people from medieval Soqotra and the Hadramawt is also unique in deriving less from early Holocene Levantine farmers and more from groups such as Late Pleistocene hunter-gatherers from the Levant (Natufians) than other mainland Arabians. This attests to migrations by early farmers having less impact in southernmost Arabia and Soqotra and provides compelling evidence that there has not been complete population replacement between the Pleistocene and Holocene throughout the Arabian Peninsula. Medieval Soqotra harboured a small population that showed qualitatively different marriage practices from modern Soqotri, with first-cousin unions occurring significantly less frequently than today., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total hip arthroplasty (THA) to reduce postoperative complications and inpatient costs. All primary THA from 2005 - 2019 were queried from the National Surgical Quality Improvement Program database, and patients were compared based on dehydration status: blood urea nitrogen (BUN): creatinine ratio (Cr) (BUN/Cr) < 20 (nondehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately dehydrated), 25 < BUN/Cr (severely dehydrated). A subgroup analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed. The analysis included 212,452 patients who underwent THA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of overall complications, postoperative anemia requiring transfusion, nonhome discharge, and increased length of stay (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of postoperative transfusion, cardiac complications, and nonhome discharge (all p < 0.01). BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning. (Journal of Surgical Orthopaedic Advances 33(1):017-025, 2024).

The rise and fall of the Roman Empire was a socio-political process with enormous ramifications for human history. The Middle Danube was a crucial frontier and a crossroads for population and cultural movement. Here, we present genome-wide data from 136 Balkan individuals dated to the 1 st millennium CE. Despite extensive militarization and cultural influence, we find little ancestry contribution from peoples of Italic descent. However, we trace a large-scale influx of people of Anatolian ancestry during the Imperial period. Between ∼250 and 550 CE, we detect migrants with ancestry from Central/Northern Europe and the Steppe, confirming that "barbarian" migrations were propelled by ethnically diverse confederations. Following the end of Roman control, we detect the large-scale arrival of individuals who were genetically similar to modern Eastern European Slavic-speaking populations, who contributed 30%-60% of the ancestry of Balkan people, representing one of the largest permanent demographic changes anywhere in Europe during the Migration Period., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity 1 . We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico 2-4 . Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions 1,5 . After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The purpose of this study was to identify modifiable medical comorbidities, laboratory markers and flaws in perioperative management that increase the risk of acute dislocation in total hip arthroplasty (THA) patients., Methods: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Demographic data, preoperative laboratory values, recorded past medical history, operative details as well as outcome and complication information were collected. The study population was divided into two cohorts: non-dislocation and dislocation patients. Statistics were performed to compare the characteristics of both cohorts and to identify risk factors for prosthetic dislocation (α < 0.05)., Results: 275,107 patients underwent primary THA in 2007 to 2020, of which 1,258 (0.5%) patients experienced a prosthetic hip dislocation. Demographics between non-dislocation and dislocation cohorts varied significantly in that dislocation patients were more likely to be female, older, with lower body mass index and a more extensive past medical history (all p < 0.05). Moreover, hypoalbuminemia and moderate/severe anemia were associated with increased risk of dislocation in a multivariate model (all p < 0.05). Finally, use of general anesthesia, longer operative time, and longer length of hospital stay correlated with greater risk of prosthetic dislocation (all p < 0.05)., Conclusions: Elderly female patients and patients with certain abnormal preoperative laboratory values are at risk for sustaining acute dislocations after index THA. Careful interdisciplinary planning and medical optimization should be considered in high-risk patients as dislocations significantly increase the risk of sepsis, cerebral vascular accident, and blood transfusions on readmission., (© 2023. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

The urban peoples of the Swahili coast traded across eastern Africa and the Indian Ocean and were among the first practitioners of Islam among sub-Saharan people 1,2 . The extent to which these early interactions between Africans and non-Africans were accompanied by genetic exchange remains unknown. Here we report ancient DNA data for 80 individuals from 6 medieval and early modern (AD 1250-1800) coastal towns and an inland town after AD 1650. More than half of the DNA of many of the individuals from coastal towns originates from primarily female ancestors from Africa, with a large proportion-and occasionally more than half-of the DNA coming from Asian ancestors. The Asian ancestry includes components associated with Persia and India, with 80-90% of the Asian DNA originating from Persian men. Peoples of African and Asian origins began to mix by about AD 1000, coinciding with the large-scale adoption of Islam. Before about AD 1500, the Southwest Asian ancestry was mainly Persian-related, consistent with the narrative of the Kilwa Chronicle, the oldest history told by people of the Swahili coast 3 . After this time, the sources of DNA became increasingly Arabian, consistent with evidence of growing interactions with southern Arabia 4 . Subsequent interactions with Asian and African people further changed the ancestry of present-day people of the Swahili coast in relation to the medieval individuals whose DNA we sequenced., (© 2023. The Author(s).)

Background: Serum alkaline phosphatase (ALP) is a biomarker for chronic low-grade inflammation along with hepatobiliary and bone disorders. High abnormal ALP levels in blood have been associated with metabolic bone disease and high bone turnover., Methods: All primary total hip and knee arthroplasties from 2005 to 2019 were queried from the National Surgical Quality Improvement Program database. Patients with available serum ALP levels were included and stratified to low (<44 IU/L), normal (44 to 147 IU/L), and high (>147 IU/L). A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor of complications., Results: The analysis included 324,592 patients, consisting of 11,427 low ALP, 305,977 normal ALP, and 7,188 high preoperative ALP level patients undergoing total joint arthroplasty. Adjusted multivariate logistic regression analysis showed high ALP level patients had an overall increased risk of readmission within 30 days of surgery compared with the control group (odds ratio [OR], 1.69; P < 0.01). High ALP patients also had an increased risk of postoperative periprosthetic fracture (OR, 1.6), postoperative wound infection (OR, 1.81), pneumonia (OR, 2.24), renal insufficiency (OR, 2.39), cerebrovascular disease (OR, 2.2), postoperative bleeding requiring transfusion (OR, 1.83), sepsis (OR, 2.35), length of stay > 2 days (OR, 1.47), Clostridium difficile infection (OR, 2.07), and discharge to a rehab facility (OR, 1.41) (all P < 0.05). A low ALP level was also associated with increased postoperative bleeding transfusion risk (OR, 1.12; P < 0.01) and developing a deep vein thrombosis (OR, 1.25; P = 0.03)., Conclusion: Abnormal serum ALP levels in patients undergoing primary total joint arthroplasty are associated with increased postoperative periprosthetic fracture risk and medical complications requiring increased length of stay and discharge to a rehabilitation facility., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Objective: Previous studies have sought to determine the effects of total knee arthroplasty (TKA) using kinematic alignment (KA) versus mechanical alignment (MA) to reproduce the native knee alignment and soft tissue envelope for improved patient satisfaction. There are limited studies that compare acute perioperative outcomes between KA and MA patients as it pertains to pain-related opioid consumption and hospital length of stay (LOS). This study aims to compare early KA and MA in restoring function and rehabilitation after surgery to reduce hospitalization and opioid consumption., Methods: A retrospective review of 42 KA and 58 MA primary TKA patients performed by a single surgeon between 2020-2021 was conducted. Demographics were controlled between groups and radiographic measurements and functional outcomes were compared. Pain was evaluated with inpatient/outpatient morphine milligram equivalents (MME) and visual analogue scale (VAS) scores. Mobility was assessed using multiple measures by a physical therapist. Mean preoperative and 3-month postoperative flexion range of motion (ROM) were analyzed, and overall complications, LOS, and non-home discharge between groups compared. Continuous variables were compared using the Wilcoxon rank-sum test, and categorical variables were compared using the chi-square or Fisher exact test. Statistical significance was set at P < 0.05., Results: KA patients had shorter LOS (1.8 vs 3.1 days) and less cumulative opioid requirements compared to MA patients (578 vs 1253 MME). On postoperative day 0, KA patients ambulated on average twice the distance of MA patients (20 vs 6.5 feet). KA patients had residual tibia component in varus (1.4° vs -0.3°), femoral component in valgus (-1.9° vs 0.2°), and valgus joint line obliquity compared with MA (-1.5° vs 0.2°). There were no significant differences between 3-month postoperative flexion arc motion, discharge destination, KOOS or SF-12 outcomes, and surgical complication rates between groups., Conclusions: By restoring the native joint line obliquity and minimizing the frequency of ligament releases, KA for TKA may improve pain relief, early mobility, and decreased length of stay compared with traditional methods of establishing neutral limb axis by MA., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Periprosthetic fractures are a devastating complication of total hip arthroplasty (THA) and are associated with significantly higher mortality rates in the postoperative period. Given the strain that periprosthetic fractures place on the patient as well as the healthcare system, identifying and optimizing medical comorbidities is essential in reducing complications and improving outcomes., Methods: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program database. Demographic data, preoperative laboratory values, medical comorbidities, hospital course, and acute complications were collected and compared between patients with and without readmission for a periprosthetic fracture. A multivariate logistic regression analysis was performed to determine associated independent risk factors for periprosthetic fractures after index THA., Results: The analysis included 275,107 patients, of which 2539 patients were readmitted for periprosthetic fractures. Patients with postoperative fractures were more likely to be older (>65 years), females, BMI >40, and increased medical comorbidities. Preoperative hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rates were independent risk factors for sustaining a periprosthetic fracture and readmission within 30 days. Modifiable patient-related factors of concurrent smoking and chronic steroid use at the time of index THA were also independent risk factors for periprosthetic fractures. Inpatient metrics of longer length of stay, operative time, and discharge to rehab predicted postarthroplasty fracture risk. Readmitted fracture patients subsequently had increased risks of developing a surgical site infection, urinary tract infection, and requiring blood transfusions., Conclusions: Patients with hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rate are at increased risk for sustaining periprosthetic fractures after THA. Preoperative optimization with close monitoring of metabolic markers and modifiable risk factors may help not only prevent acute periprosthetic fractures but also associated infection and bleeding risk with fracture readmission., (© 2022 The Authors.)

Background: As healthcare economics shifts towards outcomes-based bundled payment models, providers must understand the evolving dynamics of medical optimization and fluid resuscitation prior to elective surgery. Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total knee arthroplasty (TKA) to reduce postoperative complications and inpatient costs., Methods: All primary TKA from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database, and patients were compared based on dehydration status: Blood Urea Nitrogen Creatinine ratio (BUN/Cr) < 20 (non-dehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately-dehydrated), 25 < BUN/Cr (severely-dehydrated). A sub-group analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed., Results: The analysis included 344,744 patients who underwent TKA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of non-home discharge, postoperative transfusion, postoperative deep vein thrombosis (DVT), and increased length of stay (LOS) (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of non-home discharge, progressive renal insufficiency, urinary tract infection (UTI), postoperative transfusion, and extended LOS (all p < 0.01)., Conclusion: BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning., Level of Evidence: Level III; Retrospective Case-Control Design; Prognosis Study., (© 2023. The Author(s).)

Objectives: Perioperative dexamethasone is an effective anti-emetic and systemic analgesic in total hip arthroplasty (THA) that may reduce opioid consumption and enhance rapid recovery. However, there is no consensus on the optimal perioperative dosing that is safe and effective for faster rehabilitation and improved pain control while maintaining safe blood glucose levels., Methods: A retrospective review of 101 primary THA patients at a single institution who received perioperative dexamethasone was conducted. Patients were stratified by dexamethasone induction dosage (10 mg as high, <6mg as low) and whether a repeat dose was given 16-24 hours postoperatively. Age, gender, BMI, diabetes status, and ASA were controlled between groups. The pain was evaluated with inpatient morphine milligram equivalents (MME) requirements and visual analog scale (VAS) at 8, 16, and 24 hours postoperatively. Mobility was assessed by inpatient ambulation distance, Boston AM-PAC mobility score, and percentage of gait assistance as determined by a physical therapist. Secondary outcomes included postoperative nausea and vomiting (PONV) limiting therapy sessions, PONV requiring breakthrough anti-emetics, glucose levels, surgical site infection, wound healing complications, and discharge destination., Results: Compared to patients receiving one dose of high or low dexamethasone, patients receiving two dosages of high-dose dexamethasone had significantly further ambulation distance and lower percentage of gait assistance on postoperative day 2. A generalized linear model also predicted that any repeat dexamethasone, regardless of dosage, significantly improved ambulation distance and gait assistance compared to the one-dose cohort. There was no statistically significant difference between VAS scores, MME requirements, PONV, postoperative glucose levels >200, discharge destination, or risk of infection between groups., Conclusion: A repeat high-dose dexamethasone, the morning after surgery, may improve percentage of gait assistance and ambulation endurance on postoperative day two. There was no risk of uncontrolled glucose levels or infections compared to receiving one dose of dexamethasone at induction., Competing Interests: N/A

Trade and colonization caused an unprecedented increase in Mediterranean human mobility in the first millennium BCE. Often seen as a dividing force, warfare is in fact another catalyst of culture contact. We provide insight into the demographic dynamics of ancient warfare by reporting genome-wide data from fifth-century soldiers who fought for the army of the Greek Sicilian colony of Himera, along with representatives of the civilian population, nearby indigenous settlements, and 96 present-day individuals from Italy and Greece. Unlike the rest of the sample, many soldiers had ancestral origins in northern Europe, the Steppe, and the Caucasus. Integrating genetic, archaeological, isotopic, and historical data, these results illustrate the significant role mercenaries played in ancient Greek armies and highlight how participation in war contributed to continental-scale human mobility in the Classical world.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture 1 . The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate 2-4 . Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans-including 278 individuals from England-alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France 5,6 ., (© 2022. The Author(s).)

We present the first ancient DNA data from the Pre-Pottery Neolithic of Mesopotamia (Southeastern Turkey and Northern Iraq), Cyprus, and the Northwestern Zagros, along with the first data from Neolithic Armenia. We show that these and neighboring populations were formed through admixture of pre-Neolithic sources related to Anatolian, Caucasus, and Levantine hunter-gatherers, forming a Neolithic continuum of ancestry mirroring the geography of West Asia. By analyzing Pre-Pottery and Pottery Neolithic populations of Anatolia, we show that the former were derived from admixture between Mesopotamian-related and local Epipaleolithic-related sources, but the latter experienced additional Levantine-related gene flow, thus documenting at least two pulses of migration from the Fertile Crescent heartland to the early farmers of Anatolia.

Literary and archaeological sources have preserved a rich history of Southern Europe and West Asia since the Bronze Age that can be complemented by genetics. Mycenaean period elites in Greece did not differ from the general population and included both people with some steppe ancestry and others, like the Griffin Warrior, without it. Similarly, people in the central area of the Urartian Kingdom around Lake Van lacked the steppe ancestry characteristic of the kingdom's northern provinces. Anatolia exhibited extraordinary continuity down to the Roman and Byzantine periods, with its people serving as the demographic core of much of the Roman Empire, including the city of Rome itself. During medieval times, migrations associated with Slavic and Turkic speakers profoundly affected the region.

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra-West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe.

Introduction Although a substantial portion of the United States population has been infected with and recovered from Coronavirus Disease-19 (COVID-19), many patients may have persistent symptoms and complications from disease-driven respiratory disease, arrhythmias, and venous thromboembolism (VTE). With institutions resuming elective total joint arthroplasties (TJA), it is unclear whether a prior resolved diagnosis of COVID has any implications on postoperative outcomes. Methods All elective TJA performed in 2021 at our institution were retrospectively reviewed and a history of prior COVID+ result recorded. Baseline demographics, days from prior COVID+ result to surgery date, preoperative methicillin-resistant Staphylococcus aureus (MRSA) nares colonization, and laboratory markers were obtained to determine baseline characteristics. Postoperative estimated blood loss (EBL), length of stay (LOS), rate of revision surgery, and discharge destination were compared between groups. Perioperative and postoperative rates of VTE, urinary tract infection (UTI), pneumonia, postoperative oxygen supplementation, cardiac arrhythmia, renal disease, sepsis, and periprosthetic joint infections within six months of surgery were recorded. Results Of the 155 elective TJA performed in 2021, 24 patients had a prior COVID+ diagnosis with a mean of 253 days from positive result to surgery date. There were no significant differences in baseline demographics, comorbidities, and preoperative lab markers between groups. Surgeries on patients with a prior COVID+ had a significantly higher EBL (260 vs 175cc), but postoperative outcomes of VTE, UTI, pneumonia, oxygen supplementation requirement, nares MRSA+, cardiac disease, and infection rates between groups were similar. Bivariate logistic regression revealed increased days from COVID+ diagnosis (>6 months) to surgery date were associated with a shorter LOS. Conclusion Although a prior COVID+ diagnosis had increased intraoperative blood loss, there were no significant differences in respiratory, infectious, cardiac, and thromboembolic complications up to six months after elective TJA. This study suggests that asymptomatic C+ patients receiving elective TJA do not require more aggressive prophylactic anticoagulation or antibiotic regimens to prevent VTE or perioperative infections. As institutions around the nation resume pre-COVID rates of arthroplasty surgeries, a prior diagnosis of COVID appears to have no effects on postoperative complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Lung et al.)

Purpose: Intraoperative wound irrigation prior to closure during total joint arthroplasty (TJA) is an essential component of preventing infections and limiting health care system costs. While studies have shown the efficacy of dilute betadine in reducing infection risk, there remains concerns over its safety profile and theoretical inactivation by blood and serum. This study aims to compare infection and wound complications between chlorhexidine gluconate (CHG) and betadine lavage during TJA., Methods: All primary TJA between 2019-2021 were analyzed at a single institution, and periprosthetic joint infection (PJI), wound drainage, 30 and 90-day emergency room (ER) readmission due to wound complications, aseptic loosening, and revision surgery rate were compared between patients undergoing intraoperative CHG versus betadine lavage prior to closure. Baseline demographics were controlled, and multivariate logistic regression was performed to compare complication rates., Results: A total of 410 TJA, including 160 hip and 250 knee arthroplasties were included. Compared to the dilute betadine cohort, all TJA patients undergoing CHG lavage had a statistically significant lower 30 and 90-day emergency room readmission rate due to wound complications. Both hip and knee arthroplasty patients with CHG had a statistically significant lower rate of postoperative superficial drainage and dressing saturation at clinic follow-up, but only knee arthroplasty patients had significant decreased readmission rate for incisional wound vacuum placement and close inpatient monitoring of wound healing. Among all TJA, there was no significant association in the rate of PJI requiring return to the OR between groups., Conclusions: Although betadine is cost-effective and has been shown to reduce PJI rates, there remains concerns in the literature over soft tissue toxicity and wound healing. This study suggests CHG may be as efficacious as dilute betadine in preventing PJI while also decreasing the risk of superficial drainage and wound complications needing unplanned ER visits during the acute postoperative period., (© 2022. The Author(s).)

Micronesia began to be peopled earlier than other parts of Remote Oceania, but the origins of its inhabitants remain unclear. We generated genome-wide data from 164 ancient and 112 modern individuals. Analysis reveals five migratory streams into Micronesia. Three are East Asian related, one is Polynesian, and a fifth is a Papuan source related to mainland New Guineans that is different from the New Britain-related Papuan source for southwest Pacific populations but is similarly derived from male migrants ~2500 to 2000 years ago. People of the Mariana Archipelago may derive all of their precolonial ancestry from East Asian sources, making them the only Remote Oceanians without Papuan ancestry. Female-inherited mitochondrial DNA was highly differentiated across early Remote Oceanian communities but homogeneous within, implying matrilocal practices whereby women almost never raised their children in communities different from the ones in which they grew up.

Present-day people from England and Wales have more ancestry derived from early European farmers (EEF) than did people of the Early Bronze Age 1 . To understand this, here we generated genome-wide data from 793 individuals, increasing data from the Middle to the Late Bronze Age and Iron Age in Britain by 12-fold, and western and central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of people of England and Wales from the Iron Age, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to the Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange 2-6 . There was comparatively less gene flow from continental Europe during the Iron Age, and the independent genetic trajectory in Britain is also reflected in the rise of the allele conferring lactase persistence to approximately 50% by this time compared to approximately 7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Relatively little is known about Nubia's genetic landscape prior to the influence of the Islamic migrations that began in the late 1st millennium CE. Here, we increase the number of ancient individuals with genome-level data from the Nile Valley from three to 69, reporting data for 66 individuals from two cemeteries at the Christian Period (~650-1000 CE) site of Kulubnarti, where multiple lines of evidence suggest social stratification. The Kulubnarti Nubians had ~43% Nilotic-related ancestry (individual variation between ~36-54%) with the remaining ancestry consistent with being  introduced through Egypt and ultimately deriving from an ancestry pool like that found in the Bronze and Iron Age Levant. The Kulubnarti gene pool - shaped over a millennium - harbors disproportionately female-associated West Eurasian-related ancestry. Genetic similarity among individuals from the two cemeteries supports a hypothesis of social division without genetic distinction. Seven pairs of inter-cemetery relatives suggest fluidity between cemetery groups. Present-day Nubians are not directly descended from the Kulubnarti Nubians, attesting to additional genetic input since the Christian Period., (© 2021. The Author(s).)

Medieval Europe was repeatedly affected by outbreaks of infectious diseases, some of which reached epidemic proportions. A Late Medieval mass burial next to the Heiligen-Geist-Hospital in Lübeck (present-day Germany) contained the skeletal remains of more than 800 individuals who had presumably died from infectious disease. From 92 individuals, we screened the ancient DNA extracts for the presence of pathogens to determine the cause of death. Metagenomic analysis revealed evidence of Salmonella enterica subsp. enterica serovar Paratyphi C, suggesting an outbreak of enteric paratyphoid fever. Three reconstructed S . Paratyphi C genomes showed close similarity to a strain from Norway (1200 CE). Radiocarbon dates placed the disease outbreak in Lübeck between 1270 and 1400 cal CE, with historical records indicating 1367 CE as the most probable year. The deceased were of northern and eastern European descent, confirming Lübeck as an important trading center of the Hanseatic League in the Baltic region., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people 1,2 . Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.

Ancient DNA sampling methods-although optimized for efficient DNA extraction-are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but destructive sampling methods of the cementum often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and nine corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods., (© 2021 Harney et al.; Published by Cold Spring Harbor Laboratory Press.)

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago 1-3 . Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work 4 , we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large 5,6 . Confirming a small and interconnected Ceramic Age population 7 , we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world 1,8 .

Testing of staphylococci other than Staphylococcus aureus (SOSA) for mecA -mediated resistance is challenging. Isolates of Staphylococcus capitis , Staphylococcus haemolyticus , Staphylococcus hominis , and Staphylococcus warneri were evaluated by cefoxitin and oxacillin broth microdilution (BMD), disk diffusion (DD), and PBP2a immunoassay, and the results were compared to mecA PCR results. No phenotypic susceptibility test correlated well with PCR results across all species, although the PBP2a immunoassay yielded 100% correlation. Oxacillin BMD testing by current Clinical and Laboratory Standards Institute (CLSI) SOSA breakpoints led to 2.1% very major errors (VMEs) and 7.1% major errors (ME). Adjusting this breakpoint up by a dilution (susceptible, ≤0.5 μg/ml; resistant, ≥1.0 μg/ml) led to 2.8% VMEs and 0.3% MEs. Among species evaluated, S. haemolyticus had unacceptable VMEs with this new breakpoint (6.4%), as did S. hominis (4.0%). MEs were acceptable by this new breakpoint, ranging from 0 to 1.2%. Oxacillin DD yielded high ME rates (20.7 to 21.7%) using CLSI or European Committee on Antimicrobial Susceptibility Testing breakpoints. VMEs ranged from 0 to 5.3%. Cefoxitin BMD led to 4.9% VMEs and 1.6% MEs. Cefoxitin DD performed best when interpreted with the CLSI SOSA breakpoint, with 1.0% VMEs and 2.9% MEs. This study led CLSI to adjust the oxacillin MIC breakpoints for SOSA. Laboratories should be aware that no individual phenotypic test correlates well across all species of SOSA with mecA PCR results. Molecular testing for mecA or evaluation for PBP2a is the preferred approach., (Copyright © 2020 American Society for Microbiology.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the cause of a worldwide pandemic. Many commercial SARS-CoV-2 reverse transcription-PCR (RT-PCR) assays have received Emergency Use Authorization from the U.S. Food and Drug Administration. However, there are limited data describing their performance, in particular the performance of high-throughput SARS-CoV-2 RT-PCR systems. We analyzed the diagnostic performance of two high-throughput systems: cobas 6800 and Panther Fusion, and their associated RT-PCR assays, with a collection of 389 nasopharyngeal specimens. The overall agreement between the platforms was 96.4% (375/389). Cohen's kappa analysis rated the strength of agreement between the two platforms as "almost perfect" (κ = 0.922; standard error, 0.051). Furthermore, there was no significant difference between corresponding cycle threshold values generated on the two systems ( P value = 0.88; Student's t test). Taken together, these data imply that the two platforms can be considered comparable in terms of their clinical performance. We believe that this information will be useful for those who have already adopted these platforms or are seeking to implement high-throughput RT-PCR testing to stem the SARS-CoV-2 pandemic., (Copyright © 2020 American Society for Microbiology.)