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The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia’s megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans. Optical dating of sediments containing stone artefacts newly excavated at Madjedbebe, Australia, indicate that human occupation began around 65,000 years ago, thereby setting a new minimum age for the arrival of people in Australia. First Australian foray pushed further into the past When did humans first colonize Australia? The date of the initial landing on the continent that is now associated with cold lager and 'Waltzing Matilda' has been highly controversial. Dates from a site called Madjedbebe in northern Australia had put the presence of modern humans in Australia at between 60,000 and 50,000 years ago, but these results have since been hotly contested. Here, the results from a comprehensive program of dating of new excavations at the site confirm that people first arrived there around 65,000 years ago. The results show that humans reached Australia well before the extinction of the Australian megafauna and the disappearance of Homo floresiensis in neighbouring Indonesia.

Antisocial behavior can lead to serious social and legal consequences such as long-term involvement in criminal activities. Although there has been much research on predictors of antisocial behavior, such as perceived economic status, parental communication, impulsivity, substances, parenting styles, and parental involvement, little has been researched on how these apply to the Hispanic population. Grounded in Gottfredson and Hirschi’s general crime theory, the purpose of this nonexperimental correlational survey design study was to assess whether sensation-seeking behavior, self-control, parental monitoring, religious coping, perceived social support, and rugged resilience predicted antisocial behavior among Hispanic adults. A sample of 167 Hispanic adult participants living in the United States was included in the analyses. Bivariate correlation analyses indicated that all variables of interest, with the exception of religious coping, predicted antisocial behavior. A multiple regression analysis, however, revealed that only sensation-seeking behavior predicted antisocial behavior. The findings underscore the importance of sensation-seeking behavior as a critical factor in antisocial behavior. These results may contribute to positive social change by providing clinical psychologists and other mental health professionals with valuable insights for developing interventions to address antisocial behavior among Hispanic adults.

Over the last three decades isotope studies have become a mainstay of archaeological investigations into human diet and mobility. A small comparative sample of faunal remains often underpins these studies, used to create baselines, proxies, and provide relative information for building interpretations of the human isotope values (for example, Katzenberg 2000; Lightfoot et al. 2009; Mays 2000; Müldner 2013; Müldner and Richards 2005; Stevens et al. 2012). In recent years, the value of studying the isotope data of faunal material has been increasingly recognized. Studies of this kind have allowed detailed research into animal diets (Hamilton and Thomas 2012; Madgwick

Over the last three decades isotope studies have become a mainstay of archaeological investigations into human diet and mobility. A small comparative sample of faunal remains often underpins these studies, used to create baselines, proxies, and provide relative information for building interpretations of the human isotope values (for example, Katzenberg 2000; Lightfoot et al. 2009; Mays 2000; Müldner 2013; Müldner and Richards 2005; Stevens et al. 2012). In recent years, the value of studying the isotope data of faunal material has been increasingly recognized. Studies of this kind have allowed detailed research into animal diets (Hamilton and Thomas 2012; Madgwick

Androgens play a vital role in the main- tenance of health in normal men.Testosterone supports bone development and strength, provides anabolic effects for maintenance of lean muscle mass, and contributes to normal sexual function and libido. Circulating testosterone concentrations gradually decline as men age,

Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. Given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration （FNA） completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. Two serious adverse events （0.5%） required surgical intervention. The risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. Testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology.

The aim of this article is to provide a detailed description of the Golden Retriever Lifetime Study (GRLS), a prospective cohort study investigating nutritional, environmental, lifestyle, and genetic risk factors for cancer and other common diseases in dogs. Primary outcomes of interest include hemangiosarcoma, lymphoma, osteosarcoma, and high-grade mast cell tumors. Secondary outcomes of interest include other cancers, hypothyroidism, epilepsy, atopy, otitis externa, hip dysplasia, heart failure, and renal failure. A total of 3,044 United States Golden Retrievers aged 6 months to 2 years completed baseline enrollment from June 2012 to April 2015. As of May 31, 2021, 2,251 dogs remain engaged in the study, 352 have died, and 441 are lost to follow-up. Extensive annual questionnaires completed by owners and veterinarians gather information about lifestyle, environmental exposures, physical activity, reproductive history, behavior, diet, medications, and diagnoses. Dogs also have annual veterinary examinations and biospecimen collection (blood, serum, hair, nails, feces, urine) for biobanking. Additional reporting, including histology and tumor biobanking, is conducted for any malignancies or deaths. When an animal dies, full medical records are obtained, and necropsies are requested at owner discretion. Full or partial necropsies have been performed on 218 dogs. Questionnaire data are freely available to researchers with approved credentials who agree to a data use agreement. In addition, researchers can submit proposals to utilize biospecimens or obtain additional data.

Eosinophil-derived TGF-β has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti–IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti–IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. The thickness and density of tenascin, lumican, and procollagen III in the reticular basement membrane (RBM) were quantified immunohistochemically by confocal microscopy. Expression of TGF-β1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-β1 protein was measured in bronchoalveolar lavage (BAL) fluid by ELISA. At baseline, airway eosinophil infiltration and ECM protein deposition was increased in the RBM of asthmatics compared with nonasthmatic controls. Treating asthmatics with anti–IL-5 antibody, which specifically decreased airway eosinophil numbers, significantly reduced the expression of tenascin, lumican, and procollagen III in the bronchial mucosal RBM when compared with placebo. In addition, anti–IL-5 treatment was associated with a significant reduction in the numbers and percentage of airway eosinophils expressing mRNA for TGF-β1 and the concentration of TGF-β1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins.

Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. Given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration (FNA) completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. Two serious adverse events (0.5%) required surgical intervention. The risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. Testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology.

Myocarditis, often triggered by viral infection, may lead to heart auto‐immunity and dilated cardiomyopathy. What determines the switch between disease resolution and progression is however incompletely understood. We show that pharmacological inhibition of STAT3, the main mediator of IL‐6 signalling and of Th17‐cell differentiation, protects mice from the development of Experimental Auto‐immune Myocarditis reducing liver production of the complement component C3, and can act therapeutically when administered at disease peak. Further, we demonstrate that STAT3 is sufficient when constitutively active for triggering the onset of immune‐mediated myocarditis, involving enhanced complement C3 production and IL‐6 signalling amplification in the liver. Disease development can be prevented by C3 depletion and IL‐6 receptor neutralization. This appears to be relevant to disease pathogenesis in humans, since acute myocarditis patients display significantly elevated circulating IL‐6 and C3 levels and activated heart STAT3. Thus, aberrant IL‐6/STAT3‐mediated induction of liver acute phase response genes including C3, which occurs as a consequence of pre‐existing inflammatory conditions, might represent an important factor determining the degree of myocarditis and its clinical outcome. Graphical Abstract Aberrant IL‐6/STAT3‐mediated induction of liver acute phase response genes including C3, a consequence of pre‐existing inflammatory conditions, is involved in determining the degree of myocarditis and its clinical outcome.