Search

Crohn's disease (CD) is a chronic inflammatory disease associated with a significant burden in terms of quality of life and health care costs. It is frequently associated with several complications, including the development of intestinal strictures. Stricturing CD requires a careful multidisciplinary approach involving medical therapy and surgery, still posing a continuous management challenge; in this context, endoscopic treatment represents a valuable, in-between opportunity as a minimally invasive strategy endorsed by extensive yet heterogeneous evidence and evolving research and techniques. This review summarizes current knowledge on the role of therapeutic endoscopy in stricturing CD, focusing on evidence gaps, recent updates, and novel techniques intended for optimizing efficacy, safety, and tailoring of this approach in the view of precision endoscopy.

Malnutrition poses a critical challenge in inflammatory bowel disease, with the potential to detrimentally impact medical treatment, surgical outcomes, and general well-being. Parenteral nutrition is crucial in certain clinical scenarios, such as with patients suffering from short bowel syndrome, intestinal insufficiency, high-yielding gastrointestinal fistula, or complete small bowel obstruction, to effectively manage malnutrition. Nevertheless, research over the years has attempted to define the potential effects of parenteral nutrition on the intestinal barrier and the composition of the gut microbiota. In this narrative review, we have gathered and analyzed findings from both preclinical and clinical studies on this topic. Based on existing evidence, there is a clear correlation between short- and long-term parenteral nutrition and negative effects on the intestinal system. These include mucosal atrophic damage and immunological and neuroendocrine dysregulation, as well as alterations in gut barrier permeability and microbiota composition. However, the mechanistic role of these changes in inflammatory bowel disease remains unclear. Therefore, further research is necessary to effectively address the numerous gaps and unanswered questions pertaining to these issues.

Recently, antitumor immunotherapies have witnessed a breakthrough with the emergence of immune checkpoint inhibitors (ICIs) including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. Unfortunately, the use of ICIs has also led to the advent of a novel class of adverse events that differ from those of classic chemotherapeutics and are more reminiscent of autoimmune diseases, the immune-related adverse events (IRAEs). Herein, we performed an insight of the main IRAEs associated with ICIs, focusing on gastroenterological IRAEs and specifically on checkpoint inhibitor colitis, which represents the most widely reported IRAE to date. We comprehensively dissected the current evidence regarding pathogenesis, diagnosis, and management of ICIs-induced colitis, touching upon also on innovative therapies., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn's disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated.

Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and the disruption of the gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions., (© 2023. The Author(s).)

The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.

With the aim of providing evidence about doctor-managers' resilience during the Covid-19 pandemic, this study analyzes the characteristics of 114 doctor-managers operating within the Italian National Health Service (NHS). During the emergency, doctor-managers had to show adaptive capacities to deal with unexpected situations and develop new paradigms, procedures, and quick responses to patients' needs. This is in line with resilience, and in this perspective, it is crucial to investigate resilience determinants. The paper, therefore, provides an identikit of the resilient doctor-manager. The research was conducted between November and December 2020. Primary data were collected through an online questionnaire consisting of six sections. Participation was voluntary and anonymous. Data were analyzed using quantitative techniques and employing Stata 16. Confirmatory Factor Analysis was employed to test construct validity and scale reliability. Results show that increasing levels of individual resilience are related to increasing levels of managerial identity. Moreover, physicians' individual resilience has a positive association with commitment, knowledge diffusion, and Evidence-Based Medicine adoption. Finally, physicians' individual resilience has a negative association with their role in the university, their specialty, and their gender. The study suggests some practical implications for healtcare organizations. In general, career paths are decided primarily on competency assessment, while an important role should be devoted to behavioral characteristics. Furthermore, organizations should take care of the levels of individual commitment and encourage professional networking because both help doctor-managers cope with uncertainty. The originality of the study relies on a fresh look at all previous work. There are currently few contributions in the literature to explore and investigate resilience elements in doctor-managers during the pandemic era., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians' therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC.

Limited knowledge is available about the relationship between food allergies or intolerances and inflammatory bowel disease (IBD). Clinicians frequently encounter patients who report food allergies or intolerances, and gastroenterologists struggle distinguishing between patients with organic disorders and those with functional disorders, which the patients themselves may associate with specific dietary components. This task becomes even more arduous when managing patients with significant underlying organic conditions, like IBD. The aim of this review is to summarize and emphasize any actual associations between food allergies and intolerances and inflammatory diseases, such as ulcerative colitis and Crohn's disease. Through a narrative disceptation of the current literature, we highlight the increased prevalence of various food intolerances, including lactose, fructose, histamine, nickel, and non-celiac gluten sensitivity, in individuals with IBD. Additionally, we explore the association between increased epithelial barrier permeability in IBD and the development of food sensitization. By doing so, we aim to enhance clinicians' awareness of the nutritional management of patients with IBD when facing complaints or evidence of food allergies or intolerances.

Background: Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic small-vessel vasculitis (IgAV) that typically presents with a variable tetrad of symptoms. HSP if often preceded by respiratory tract infections, vaccinations, drugs or malignancies. During the recent COVID-19 pandemic multiples cases of HSP have been described after both infection and vaccination for SARS-CoV2. This study aims to perform a systematic review of literature and describe an additional complicated case of de-novo HSP appeared after the administration of the third dose of a mRNA-SARS-CoV2 vaccination., Methods: Electronic bibliographic research was performed to identify all the original reports describing cases of de-novo HSP or IgAV appeared after respiratory infection or vaccine administration for SARS-CoV2. We included all case series or case reports of patients who respected our inclusion and exclusion criteria., Results: Thirty-eight publications met our pre-defined inclusion criteria, for an overall number of 44 patients. All patients presented with palpable purpura variable associated with arthralgia, abdominal pain or renal involvement. Increased levels of inflammation markers, mild leukocytosis and elevated D-dimer were the most common laboratory findings. Up to 50% of patients presented proteinuria and/or hematuria. Almost all skin biopsies showed leukocytoclastic vasculitis, with IgA deposits at direct immunofluorescence in more than 50% of cases., Conclusions: Our results suggest that the immune response elicited by SARS-CoV2 vaccine or infection could play a role in the development of HSP. Current research suggests a possible role of IgA in immune hyperactivation, highlighted by early seroconversion to IgA found in some COVID-19 patients who develop IgA vasculitis., (© 2023. The Author(s).)

CMV infection is still a matter of concern in IBD patients, especially regarding the disease's relapse management. Why IBD patients, particularly those affected by ulcerative colitis, are more susceptible to CMV reactivation is not totally explained, although a weakened immune system could be the reason. Various techniques, ranging from serology to histology, can be employed to detect intestinal CMV infection; however, there is currently disagreement in the literature regarding the most effective diagnostic test. Furthermore, CMV involvement in steroid resistance has been broadly discussed, but whether CMV infection is a cause or consequence of the disease severity and, consequently, steroid refractoriness is still debated. Its potential contribution to the lack of response to advanced therapy and small molecules must be more valued and wholly explored. In this review, we look at the actual literature on CMV in IBD patients, and we suggest a pragmatic algorithm for clinical practice management of CMV infection.

Background: Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific personality traits. Despite this, there are few data about personality profiles' characterization in UC patients and about correlation of their psychopathological profile with their intestinal microbiota.The aim of our study is to analyze the psychopathological and personality profile of UC patients and correlate it with specific signatures of their gut microbiota., Methods: This is a prospective interventional longitudinal cohort study. We enrolled consecutive patients affected by UC attending to the IBD Unit of Center for Digestive Disease of "A. Gemelli" IRCCS Hospital in Rome and a group of healthy subjects, matched for specific characteristics. Each patient was evaluated by a gastroenterologist and a psychiatrist. Moreover, all participants underwent psychological tests and a collection of stool samples., Results: We recruited 39 UC patients and 37 healthy subjects. Most patients showed high level of alexithymia, anxiety symptoms, depressive symptoms, as well as neuroticism and hypochondria, with obsessive-compulsive features at the behavioral level, which significantly impaired their quality of life and abilities at work. Gut microbiota analysis in UC patients demonstrated an increase in actinobacteria, Proteobacteria and Saccharibacteria (TM7), with a reduction in verrucomicrobia, euryarchaeota and tenericutes., Conclusions: Our study confirmed the presence of high levels of psycho-emotional distress in UC patients, alongside alterations of the intestinal microbiota, and highlighted some families and genera of bacteria (Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae) as potential markers of an altered gut-brain axis in these patients., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.

Population size history is essential for studying human evolution. However, ancient population size history during the Pleistocene is notoriously difficult to unravel. In this study, we developed a fast infinitesimal time coalescent process (FitCoal) to circumvent this difficulty and calculated the composite likelihood for present-day human genomic sequences of 3154 individuals. Results showed that human ancestors went through a severe population bottleneck with about 1280 breeding individuals between around 930,000 and 813,000 years ago. The bottleneck lasted for about 117,000 years and brought human ancestors close to extinction. This bottleneck is congruent with a substantial chronological gap in the available African and Eurasian fossil record. Our results provide new insights into our ancestry and suggest a coincident speciation event.

Inflammatory bowel diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from the origin cell and able to circulate into the bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also play a role in IBD. In this review, we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

The gut microbiota is a pivotal actor in the maintenance of the balance in the complex interconnections of hepato-biliary-pancreatic system. It has both metabolic and immunologic functions, with an influence on the homeostasis of the whole organism and on the pathogenesis of a wide range of diseases, from non-neoplastic ones to tumorigenesis. The continuous bidirectional metabolic communication between gut and hepato-pancreatic district, through bile ducts and portal vein, leads to a continuous interaction with translocated bacteria and their products. Chronic liver disease and pancreatic disorders can lead to reduced intestinal motility, decreased bile acid synthesis and intestinal immune dysfunction, determining a compositional and functional imbalance in gut microbiota (dysbiosis), with potentially harmful consequences on the host's health. The modulation of the gut microbiota by antibiotics represents a pioneering challenge with striking future therapeutic opportunities, even in non-infectious diseases. In this setting, antibiotics are aimed at harmonizing gut microbial function and, sometimes, composition. A more targeted and specific approach should be the goal to pursue in the future, tailoring the treatment according to the type of microbiota modulation to be achieved and using combined strategies.

Complete Neanderthal skeletons are almost unique findings. A very well-preserved specimen of this kind was discovered in 1993 in the deepest recesses of a karstic system near the town of Altamura in Southern Italy. We present here a detailed description of the cranium, after we virtually extracted it from the surrounding stalagmites and stalactites. The morphology of the Altamura cranium fits within the Neanderthal variability, though it retains features occurring in more archaic European samples. Some of these features were never observed in Homo neanderthalensis, i.e. in fossil specimens dated between 300 and 40 ka. Considering the U-Th age we previously obtained (>130 ka), the morphology of Altamura suggests that the archaic traits it retains may have been originated by geographic isolation of the early Neanderthal populations from Southern Italy., (© 2023. The Author(s).)

Since prehistoric times, Italy has represented a bridge between peoples, genes and cultures. Its peculiar geographical position explains why: it is located in the center of the Mediterranean Sea, flanked by the Balkans and the Hellenic Peninsula to the east, Iberia to the west and surrounded by North Africa to the south and central Europe to the north. This makes Italy of extraordinary interest for the study of some different aspects of human diversity. Here we overview current knowledge regarding the relationships between the structure of the genetic variation of Italian populations and the geographical, ecological and cultural factors that have characterized their evolutionary history. Human presence in Italian territory is deeply rooted in the past. Lithic artifacts produced by the genus Homo and remains of Homo sapiens are among the earliest to have been found on the continent, as shown by the lithic industry of Pirro Nord (between 1.3 and 1.6 Mya) and the dental remains of the "Grotta del Cavallo" (between 45 and 43 Kya). Genetic and genomic studies relating to existing and extinct human groups have shed light on the migrations from Europe, Africa and Asia that created the ancient layers of the genetic structure of today's Italian populations, especially before the Iron Age. The important role of isolation (genetic and cultural) in shaping genetic structure is clearly visible in the patterns of intra- and inter-population diversity observed among Italian ethno-linguistic minorities that settled on the peninsula and on the major islands until the 19th century. Finally, selective pressures have likely driven the distribution of originally adaptive variants and haplotypes that now confer protection or susceptibility to major diseases such as diabetes and cardiovascular disease (in northern Italy) and tuberculosis and leprosy (in the south). What emerges is a picture where the combined effects of migration, isolation and natural selection generated by the interplay of geography, environment and culture have shaped a complex pattern of human diversity that is unique in Europe and which goes hand in hand with today's rich animal and plant biodiversity. In a nutshell, scientific evidence and cultural heritage paint Italy as a place with extremely diverse environments where distant peoples have met since the deep past, bringing and sharing genes and ideas.

Purpose: Self-efficacy, or a person's belief in his/her ability to perform specific tasks, has been correlated with workplace performance and role adjustments. Despite its relevance, and numerous studies of it in the management literature, evidence regarding its function in professionals employed in hybrid roles, such as doctor-managers, is lacking. The aim of this study was to fill this gap by exploring the mediating effect of physicians' managerial attitude on the relationship between their self-efficacy and workplace performance., Design/methodology/approach: Primary and secondary data from 126 doctor-managers were obtained from the Italian National Health Service. A structural equation modeling approach was used for analysis., Findings: This study's results provide for the first time empirical evidence about a surprisingly little-analyzed topic: how physicians' managerial attitude mediates the relationship between their self-efficacy and workplace performance. The study offers important evidence both for scholars and organizations., Practical Implications: This study's results provide valuable input for the human resources management of hybrid roles in professional-based organizations, suggesting a systematic provision of feedback about doctor-managers' performance, the adoption of a competence approach for their recruitment, and a new design of doctor-managers' career paths., Originality/value: The authors provide new evidence about the importance of managerial traits for accountable healthcare organizations, documenting that behavioral traits of physicians enrolled into managerial roles matter for healthcare organizations success., (© Federica Morandi, Simona Leonelli and Fausto Di Vincenzo.)

Inflammatory bowel diseases (IBD) and microscopic colitis are chronic immune-mediated inflammatory disorders that affect the gastroenterological tract and arise from a complex interaction between the host's genetic risk factors, environmental factors, and gut microbiota dysbiosis. The precise mechanistic pathways interlinking the intestinal mucosa homeostasis, the immunological tolerance, and the gut microbiota are still crucial topics for research. We decided to deeply analyze the role of bile acids in these complex interactions and their metabolism in the modulation of gut microbiota, and thus intestinal mucosa inflammation. Recent metabolomics studies revealed a significant defect in bile acid metabolism in IBD patients, with an increase in primary bile acids and a reduction in secondary bile acids. In this review, we explore the evidence linking bile acid metabolites with the immunological pathways involved in IBD pathogenesis, including apoptosis and inflammasome activation. Furthermore, we summarize the principal etiopathogenetic mechanisms of different types of bile acid-induced diarrhea (BAD) and its main novel diagnostic approaches. Finally, we discuss the role of bile acid in current and possible future state-of-the-art therapeutic strategies for both IBD and BAD.

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli . Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC ( n = 16) were enrolled and compared with healthy female subjects ( n = 15) and patients with chronic gastrointestinal (GI) disorders ( n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.

Background and Objective: The aim of this narrative review is to analyze whether or not artificial intelligence (AI) and its subsets are implemented in current clinical anesthetic practice, and to describe the current state of the research in the field. AI is a general term which refers to all the techniques that enable computers to mimic human intelligence. AI is based on algorithms that gives machines the ability to reason and perform functions such as problem-solving, object and word recognition, inference of world states, and decision-making. It includes machine learning (ML) and deep learning (DL)., Methods: We performed a narrative review of the literature on Scopus, PubMed and Cochrane databases. The research string comprised various combinations of "artificial intelligence", "machine learning", "anesthesia", "anesthesiology". The databases were searched independently by two authors. A third reviewer would mediate any disagreement the results of the two screeners., Key Content and Findings: The application of AI has shown excellent results in both anesthesia and in operating room (OR) management. In each phase of the perioperative process, pre-, intra- and postoperative ones, it is able to perform different and specific tasks, using various techniques., Conclusions: Thanks to the use of these new technologies, even anesthesia, as it is happening for other disciplines, is going through a real revolution, called Anesthesia 4.0. However, AI is not free from limitations and open issues. Unfortunately, the models created, provided they have excellent performance, have not yet entered daily practice. Clinical impact analyzes and external validations are needed before this happens. Therefore, qualitative research will be needed to better understand the ethical, cultural, and societal implications of integrating AI into clinical workflows., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-7031/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Lipopolysaccharide (LPS) is a peculiar component of the outer membrane (OM) of many Gram-negative bacteria that renders these bacteria highly impermeable to many toxic molecules, including antibiotics. LPS is assembled at the OM by a dedicated intermembrane transport system, the Lpt (LPS transport) machinery, composed of seven essential proteins located in the inner membrane (IM) (LptB 2 CFG), periplasm (LptA), and OM (LptDE). Defects in LPS transport compromise LPS insertion and assembly at the OM and result in an overall modification of the cell envelope and its permeability barrier properties. LptA is a key component of the Lpt machine. It connects the IM and OM sub-complexes by interacting with the IM protein LptC and the OM protein LptD, thus enabling the LPS transport across the periplasm. Defects in Lpt system assembly result in LptA degradation whose stability can be considered a marker of an improperly assembled Lpt system. Indeed, LptA recruitment by its IM and OM docking sites requires correct maturation of the LptB 2 CFG and LptDE sub-complexes, respectively. These quality control checkpoints are crucial to avoid LPS mistargeting. To further dissect the requirements for the complete Lpt transenvelope bridge assembly, we explored the importance of LPS presence by blocking its synthesis using an inhibitor compound. Here, we found that the interruption of LPS synthesis results in the degradation of both LptA and LptD, suggesting that, in the absence of the LPS substrate, the stability of the Lpt complex is compromised. Under these conditions, DegP, a major chaperone-protease in Escherichia coli , is responsible for LptD but not LptA degradation. Importantly, LptD and LptA stability is not affected by stressors disturbing the integrity of LPS or peptidoglycan layers, further supporting the notion that the LPS substrate is fundamental to keeping the Lpt transenvelope complex assembled and that LptA and LptD play a major role in the stability of the Lpt system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martorana, Moura, Sperandeo, Di Vincenzo, Liang, Toone, Zhou and Polissi.)

The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human-environment interactions during Humankind history., (© 2021. The Author(s).)

Background: Accountable care has changed organizational models adopted by health care organizations profoundly and, consequently, the skill set required for doctor-managers who have become middle managers and must deal with the operational management of their units. Doctor-managers must carry out clinical tasks as well as tasks related to budgeting, goal setting, and performance evaluation. The performance evaluation bias, defined as the misalignment between a ward unit's objective performance (as assessed by technical bodies or agencies) and self-assessed performance by the head of the unit, may have serious consequences for individuals and organizations., Purpose: The aim of this study was to identify determinants of performance appraisal bias based on the mismatch between self-reported and official performance data. Specifically, we analyzed the role played by managerial behavior, training, engagement, and perceived organizational support at the individual level, as well as the particular unit's task diversity, complexity, and predictability., Methodology: We collected primary and secondary data referable to a population of ward unit heads in the Italian National Health Service. A linear regression model predicting performance appraisal bias was employed., Findings: High levels of engagement and perceived organizational support were associated with reduced performance appraisal bias, whereas high levels of predictability and task diversity were associated with increased degree of error. Doctor-managers attending training programs in health care management and ward unit task complexity did not affect bias significantly., Practice Implications: Policy makers and hospital managers should provide heads of units with tools that enable them to conduct ongoing monitoring and accurate appraisal of performance. Doctor-manager performance appraisal bias may be diminished by a perception of having support of the organization and direct superiors. Training programs can be revised to incorporate performance appraisal, and good performance may be incentivized with rewards., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Accountable care has profoundly changed the organizational models adopted by health care organizations and, consequently, the skill set required for doctor-managers who have become middle managers and must deal with the operational management of their units. The aim of this study was to identify the psychological microfoundations (i.e., traits) of physicians' managerial attitude. Specifically, we analysed the roles played by narcissism, specialization choices and identification with the organization., Methods: We collected primary data on a population of ward unit heads in the Italian National Health Service. A logistic regression model predicting the levels of managerial attitude was employed., Results: The results indicate that high levels of narcissism and identification with the organization are related to higher managerial attitude (instead of clinical attitude). Additionally, we found that physicians with a technique-oriented specialization present a higher probability of manifesting managerial attitude (in comparison to clinical attitude)., Conclusions: Hospital managers can benefit from the use of these findings by developing a strategic approach to human resource management that allows them to identify, train and select the right mix of technical knowledge and managerial skills for middle-management roles.

The Neanderthal specimen from Lamalunga Cave, near Altamura (Apulia, Italy), was discovered during a speleological survey in 1993. The specimen is one of the most complete fossil hominins in Europe and its state of preservation is exceptional, although it is stuck in calcareous concretions and the bones are mostly covered by calcite depositions. Nevertheless, it is possible to carry out some observations on craniodental features that have not previously been described. In this work, we present an account of the oral cavity, made possible by the use of a videoscope, which allowed us to reach some hidden parts of the mandible and palate. This is the first detailed overview of the teeth and maxillary bones of the Neanderthal skeleton from Altamura. The dentition is almost complete. However, two teeth (upper right P3 and upper left M1) were lost ante mortem and four teeth (lower right I1 and P3 and lower left I1 and I2) were lost most probably post mortem. Dental wear is marked. The erupted M3s and the inversion of the compensating curve of Wilson in the M1s and M2s but not in the M3s suggest that the individual is fully adult, but not old. Although most of the teeth have their roots exposed for several millimeters, the periodontal bone appears to be in good condition overall, except in correspondence of the two ante-mortem tooth losses. X-rays of the anterior teeth show a periapical lesion, probably linked to the advanced dental wear. We also observed a weak expression of taurodontism in the posterior dentition and the presence of a retromolar space, features consistent with an attribution to the Neanderthal hypodigm; this attribution is also supported by aspects of the cranial morphology, the morphometric analysis of the scapula and preliminary mtDNA data. There is also a well-developed palatine torus, to the best of our knowledge a feature not previously described in Neanderthals., Competing Interests: The authors have declared that no competing interests exist.

The arrival of the Longobards in Northern Italy in 568 CE marked a period of renewed political stability in the Peninsula after the collapse of the Western Roman Empire. The trajectory of the spread of Longobards in Italy across the Alps and into the South is known from many literary sources. However, their mobility and residence patterns at a population level remain to be fully understood. Here we present a multi-isotopic analysis ( 87 Sr/ 86 Sr and 18 O/ 16 O) of 39 humans and 14 animals buried at the Longobard necropolis of Povegliano Veronese (VR, Italy; 6th-8th century CE), to address mode and tempo of the spread of this population in the Peninsula. The geographical location of Povegliano Veronese plays a key role: the site lies along the Via Postumia, which was one of the main ancient Roman roads of Northern Italy, representing an important route in post-classical Italy. The integration of isotopic data with the archaeological evidence allowed us to determine the presence of individuals from at least three different regions of origin, building a diachronic map of the dynamics of mobility of this group in northern Italy.

In recent years, the renewed interest in environmental issues has gradually required manufacturers to simultaneously pursue a more rational use of resources and a reduction in wastes production. New strategies, technologies and organisational innovations must be therefore conceived to "create more value with less impact" (WBCSD, 2010). An interesting and promising perspective for achieving internal efficiency, market effectiveness and environmental eco-efficiency is that of integrating the environmental variable in the Lean Production (LP) paradigm. Scholars and practitioners have been working for some years in this direction of eco-innovation. The present article aims at obtaining a quali/quantitative overview of Lean and Clean(er) production (L&C) research through a bibliometric and network analysis, by using a scientific literature database; in particular, it investigates how Clean(er) Production research and publications are progressively embedded in the field of LP, what are the main topics in this sub-field and common research themes. A comprehensive picture was made by analysing data concerning publications, authors, affiliations, and the countries of origin. Evolutionary profiles, major topics investigated, leading authors and collaborations have been reported. The results also reveal promising spaces for the development of L&C production research, in order to achieve economic and environmental benefits., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Longobard necropolis of Povegliano Veronese dates from the 6th to the 8th centuries AD. Among the 164 tombs excavated, the skeleton of an older male shows a well-healed amputated right forearm. The orientation of the forearm fracture suggests an angled cut by a single blow. Reasons why a forearm might be amputated include combat, medical intervention, and judicial punishment. As with other amputation cases reported in literature, this one exhibits both healing and osteoblastic response. We argue that the forelimb stump morphology suggests the use of a prosthesis. Moreover, dental modification of RI2 shows considerable wear and smoothing of the occlusal surface, which points to dental use in attaching the prosthesis to the limb. Other indications of how this individual adjusted to his amputated condition includes a slight change in the orientation of the right glenoid fossa surface, and thinning of right humeral cortical bone. This is a remarkable example in which an older male survived the loss of a forelimb in pre-antibiotic era. We link archaeological remains found in the tomb (buckle and knife) with the biological evidence to show how a combined bioarchaeological approach can provide a clearer interpretation of the life history of an individual.

Background: Despite an extensive body of knowledge exists on network outcomes and on how hospital network structures may contribute to the creation of outcomes at different levels of analysis, less attention has been paid to understanding how and why hospital organizational networks evolve and change. The aim of this paper is to study the dynamics of networking behaviors of hospital organizations., Methods: Stochastic actor-based model for network dynamics was used to quantitatively examine data covering six-years of patient transfer relations among 35 hospital organizations. Specifically, the study investigated about determinants of patient transfer evolution modeling partner selection choice as a combination of multiple organizational attributes and endogenous network-based processes., Results: The results indicate that having overlapping specialties and treating patients with the same case-mix decrease the likelihood of observing network ties between hospitals. Also, results revealed as geographical proximity and membership of the same LHA have a positive impact on the networking behavior of hospitals organizations, there is a propensity in the network to choose larger hospitals as partners, and to transfer patients between hospitals facing similar levels of operational uncertainty., Conclusions: Organizational attributes (overlapping specialties and case-mix), institutional factors (LHA), and geographical proximity matter in the formation and shaping of hospital networks over time. Managers can benefit from the use of these findings by clearly identifying the role and strategic positioning of their hospital with respect to the entire network. Social network analysis can yield novel information and also aid policy makers in the formation of interventions, encouraging alliances among providers as well as planning health system restructuring.

Many fossil specimens exhibit deformations caused by taphonomic processes. Due to these deformations, even important specimens have to be excluded from morphometric analyses, impoverishing an already poor paleontological record. Techniques to retrodeform and virtually restore damaged (i.e. deformed) specimens are available, but these methods genenerally imply the use of a sparse set of bilateral landmarks, ignoring the fact that the distribution and amount of control points directly affects the result of the retrodeformation. We propose a method developed in the R environment and available in the R-package "Morpho" that, in addition to the landmark configurations, also allows using a set of semi-landmarks homogeneously distributed along curves and on surfaces. We evaluated the outcome of the retrodeformation, regarding the number of semi-landmarks used and its robustness against asymmetric noise, based on simulations using a virtually deformed gorilla cranium. Finally, we applied the method to a well-known Neanderthal cranium that exhibits signs of taphonomically induced asymmetry.

The evolutionary relationship between the base and face of the cranium is a major topic of interest in primatology. Such areas of the skull possibly respond to different selective pressures. Yet, they are often said to be tightly integrated. In this paper, we analyzed shape variability in the cranial base and the facial complex in Cercopithecoidea and Hominoidea. We used a landmark-based approach to single out the effects of size (evolutionary allometry), morphological integration, modularity, and phylogeny (under Brownian motion) on skull shape variability. Our results demonstrate that the cranial base and the facial complex exhibit different responses to different factors, which produces a little degree of morphological integration between them. Facial shape variation appears primarily influenced by body size and sexual dimorphism, whereas the cranial base is mostly influenced by functional factors. The different adaptations affecting the two modules suggest they are best studied as separate and independent units, and that-at least when dealing with Catarrhines-caution must be posed with the notion of strong cranial integration that is commonly invoked for the evolution of their skull shape., (© 2017 Wiley Periodicals, Inc.)

The Ceprano calvarium was discovered in fragments on March 1994 near the town of Ceprano in southern Latium (Italy), embedded in Middle Pleistocene layers. After reconstruction, its morphological features suggests that the specimen belongs to an archaic variant of H. heidelbergensis, representing a proxy for the last common ancestor of the diverging clades that respectively led to H. neanderthalensis and H. sapiens. Unfortunately, the calvarium was taphonomically damaged. The postero-lateral vault, in particular, appears deformed and this postmortem damage may have influenced previous interpretations. Specifically, there is a depression on the fragmented left parietal, while the right cranial wall is warped and angulated. This deformation affected the shape of the occipital squama, producing an inclination of the transverse occipital torus. In this paper, after X-ray microtomography (μCT) of both the calvarium and several additional fragments, we analyze consistency and pattern of the taphonomic deformation that affected the specimen, before the computer-assisted retrodeformation has been performed; this has also provided the opportunity to reappraise early attempts at restoration. As a result, we offer a revised interpretation for the Ceprano calvarium's original shape, now free from the previous uncertainties, along with insight for its complex depositional and taphonomic history.

The native groups of Patagonia have relied on a hunter-gatherer economy well after the first Europeans and North Americans reached this part of the world. The large exploitation of marine mammals (i.e., seals) by such allochthonous groups has had a strong impact on the local ecology in a way that might have forced the natives to adjust their subsistence strategies. Similarly, the introduction of new foods might have changed local diet. These are the premises of our isotopic-based analysis. There is a large set of paleonutritional investigations through isotopic analysis on Fuegians groups, however a systematic exploration of food practices across time in relation to possible pre- and post-contact changes is still lacking. In this paper we investigate dietary variation in hunter-gatherer groups of Tierra del Fuego in a diachronic perspective, through measuring the isotopic ratio of carbon (∂13C) and nitrogen (∂15N) in the bone collagen of human and a selection of terrestrial and marine animal samples. The data obtained reveal an unexpected isotopic uniformity across prehistoric and recent groups, with little variation in both carbon and nitrogen mean values, which we interpret as the possible evidence of resilience among these groups and persistence of subsistence strategies, allowing inferences on the dramatic contraction (and extinction) of Fuegian populations.

African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

In 1993, a fossil hominin skeleton was discovered in the karst caves of Lamalunga, near Altamura, in southern Italy. Despite the fact that this specimen represents one of the most extraordinary hominin specimens ever found in Europe, for the last two decades our knowledge of it has been based purely on the documented on-site observations. Recently, the retrieval from the cave of a fragment of bone (part of the right scapula) allowed the first dating of the individual, the quantitative analysis of a diagnostic morphological feature, and a preliminary paleogenetic characterization of this hominin skeleton from Altamura. Overall, the results concur in indicating that it belongs to the hypodigm of Homo neanderthalensis, with some phenetic peculiarities that appear consistent with a chronology ranging from 172 ± 15 ka to 130.1 ± 1.9 ka. Thus, the skeleton from Altamura represents the most ancient Neanderthal from which endogenous DNA has ever been extracted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Previous studies have shown that referral networks encompass important mechanisms of coordination and integration among hospitals, which enhance numerous organizational-level benefits, such as productivity, efficiency, and quality of care. The present study advances previous research by demonstrating how hospital referral networks influence patient readmissions. Data include 360,697 hospitalization events within a regional community of hospitals in the Italian National Health Service. Multilevel hierarchical regression analysis tests the impacts of referral networks' structural characteristics on patient hospital readmissions. The results demonstrate that organizational centrality in the overall referral network and ego-network density have opposing effects on the likelihood of readmission events within hospitals; greater centrality is negatively associated with readmissions, whereas greater ego-network density increases the likelihood of readmission events. Our findings support the (re)organization of healthcare systems and provide important indications for policymakers and practitioners., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Modern healthcare is characterized by high complexity due to the proliferation of specialties, professional roles, and priorities within organizations. To perform clinical interventions, knowledge distributed across units, directorates and individuals needs to be integrated. Formal and/or informal mechanisms may be used to coordinate knowledge and tasks within organizations. Although the literature has recently considered the role of physicians' professional networks in the diffusion of knowledge, several concerns remain about the mechanisms through which these networks emerge within healthcare organizations. The aim of the present paper is to explore the impact of institutional and professional homophilies on the formation of interphysician professional networks., Methods: We collected data on a community of around 300 physicians working at a local health authority within the Italian National Health Service. We employed multiple regression quadratic assignment procedures to explore the extent to which institutional and professional homophilies influence the formation of interphysician networks., Results: We found that both institutional and professional homophilies matter in explaining interphysician networks. Physicians who had similar fields of interest or belonged to the same organizational structure were more likely to establish professional relationships. In addition, professional homophily was more relevant than institutional affiliation in explaining collaborative ties., Conclusions: Our findings have organizational implications and provide useful information for managers who are responsible for undertaking organizational restructuring. Healthcare executives and administrators may want to consider the structure of advice networks while adopting new organizational structures.

The Middle Pastoral human remains from Wadi Takarkori in the Libyan Acacus mountains (Fezzan) are exceptionally preserved partial mummies ranging between 6100 and 5000 uncal years BP; this small sample represents the most ancient of its kind ever found. In this report, we present a survey of the skeletal anatomy of these mummifed corpses, based on high resolution CT-scan data, including a preliminary phenetic interpretation of their cranial morphology.

Physicians around the globe are increasingly encouraged to adopt guidelines, protocols and other scientific material when making clinical decisions. Extant research suggests that the clinicians' propensity to use evidence-based medicine (EBM) is strongly associated with the professional collaborative networks they establish and maintain with peers. In this paper we explore whether and how the connectedness of primary care physicians with colleagues working in hospital settings is related to their frequency of EBM use in clinical practice. We used survey data from 104 pediatricians working in five local health authorities in the Italian NHS. Social network and attributional data concerning single physicians, as well as their self-reported frequency of EBM use, were collected for three major pathologies in pediatric care: asthmatic, gastro-enteric and urinary pathologies. Ordered regression analysis was employed. Our findings documented a positive association between the number of physicians' relationships with hospital colleagues and the frequency of use EBM. Results also indicated that physicians' organizational affiliations influence the frequency of EBM use. Finally, contrary to our expectations, it was found that clinicians' affiliation to formal collaborative arrangements is at odds with the likelihood of reporting higher frequency of EBM use., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: In the early 1990s, the governments of many countries took the first steps toward introducing market forces into the provision of health care services, with the aim of increasing hospital efficiency and quality of care. Several reforms have been developed to strengthen the role of competition, giving rise to forms of "managed competition." As a result, the environment in which providers operate and perform is increasingly characterized by conditions of competition, rather than of cooperation., Purpose: The aim of this study was to analyze the evolution of competitive interdependences among hospitals and the impact of organizational demographics on pair-wise competition., Methodology: Longitudinal data on competitive interdependences collected within a regional community of hospital organizations in the Italian National Health Service were analyzed. Stochastic actor-based models designed for estimating network dynamics were used to study organizational characteristics influencing patterns of change in competitive interdependences., Findings: The results indicated that interorganizational cooperation is a significant predictor of competitive interdependences, that pair-wise competition among hospitals is primarily local, and that competitive interdependences are more likely to occur between local providers that differed with respect to performance and volume of activity., Practice Implications: Exploring the evolution of competitive interdependences between hospitals is salient for administrators who are interested in increasing their understanding of the whole market. They can better identify direct competitors by paying particular attention to those organizational characteristics that likely predict competitive actions. This approach is also important for policy makers, which may be interested in better targeting hospital restructuring interventions while implementing procompetition reforms.

Background: Policymakers stimulate competition in universalistic health-care systems while encouraging the formation of service provision networks among hospital organizations. This article addresses a gap in the extant literature by empirically analyzing simultaneous collaboration and competition between hospitals within the Italian National Health Service, where important procompetition reforms have been implemented., Purpose: To explore how rising competition between hospitals relates to their propensity to collaborate with other local providers., Methods: Longitudinal data on interhospital collaboration and competition collected in an Italian region from 2003 to 2007 are analyzed. Social network analysis techniques are applied to study the structure and dynamics of interhospital collaboration. Negative binomial regressions are employed to explore how interhospital competition relates to the collaborative network over time., Results: Competition among providers does not hinder interhospital collaboration. Collaboration is primarily local, with resource complementarity and differentials in the volume of activity and hospital performance explaining the propensity to collaborate., Conclusions: Formation of collaborative networks among hospitals is not hampered by reforms aimed at fostering market forces. Because procompetition reforms elicit peculiar forms of managed competition in universalistic health systems, studies are needed to clarify whether the positive association between interhospital competition and collaboration can be generalized to other health-care settings., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Although the shape of the scapular glenoid fossa (SGF) may be influenced by epigenetic and developmental factors, there appears to be strong genetic control over its overall form, such that variation within and between hominin taxa in SGF shape may contain information about their evolutionary histories. Here we present the results of a geometric morphometric study of the SGF of the Neanderthal Vi-209 from Vindjia Cave (Croatia), relative to samples of Plio-Pleistocene, later Pleistocene, and recent hominins. Variation in overall SGF shape follows a chronological trend from the plesiomorphic condition seen in Australopithecus to modern humans, with pre-modern species of the genus Homo exhibiting intermediate morphologies. Change in body size across this temporal series is not linearly directional, which argues against static allometry as an explanation. However, life history and developmental rates change directionally across the series, suggesting an ontogenetic effect on the observed changes in shape (ontogenetic allometry). Within this framework, the morphospace occupied by the Neanderthals exhibits a discontinuous distribution. The Vindija SGF and those of the later Near Eastern Neanderthals (Kebara and Shanidar) approach the modern condition and are somewhat segregated from both northwestern European (Neandertal and La Ferrassie) and early Mediterranean Neanderthals (Krapina and Tabun). Although more than one scenario may account for the pattern seen in the Neanderthals, the data is consistent with palaeogenetic evidence suggesting low levels of gene flow between Neanderthals and modern humans in the Near East after ca. 120-100 ka (thousands of years ago) (with subsequent introgression of modern human alleles into eastern and central Europe). Thus, in keeping with previous analyses that document some modern human features in the Vindija Neanderthals, the Vindija G(3) sample should not be seen as representative of 'classic'--that is, unadmixed, pre-contact--Neanderthal morphology., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: To improve efficiency and quality, a number of policies have recently been implemented to increase competition and cooperation within the health systems of many countries. We theorize how hospital performance, measured as productivity, is contingent upon network embeddedness, the extent to which a hospital is involved in a network of interconnected interorganizational relationships., Purpose: The aim of this study was to explore the effects on hospital productivity resulting from both collaborative network ties and competitive relationships between providers., Methodology: We used panel data collected between 2003 and 2007 from 35 hospitals in Abruzzo, one of the most populated regions of central Italy. We used secondary data of hospital activities regarding both clinical and administrative aspects. For each year, we examined the intensity of interhospital competition and the unique position each provider has within a larger network of relationships with other hospitals. Other idiosyncratic organizational characteristics were examined as well., Findings: Our results show that hospital productivity is negatively related to the degree of competition that a hospital faces and positively related to the degree with which hospitals establish collaborative relationships. We also found that the negative impact on hospital productivity due to competition was lessened when hospitals were more likely to create cooperative network ties., Practice Implications: Because interhospital collaboration and competition are related to hospital productivity, they should constitute a core element in the strategic planning of a hospital's operation. Health administrators should implement policies that favor collaborative network ties at the regional level and mitigate interorganizational rivalries when establishing collaborative relationships with local competitors.