Recurrence and return to duty following patellar instability events in military personnel.

INTRODUCTION: Military service members experience patellar dislocations at a rate 10 times that of civilians. The purpose of this study was to determine the return to duty rate of active duty military personnel following first-time or recurrent patellar dislocation. Secondary goals were to identify patient variables and radiographic parameters associated with recurrent instability and requiring medical separation from military service. METHODS: The Military Health System Data Repository was used to identify all active-duty military personnel who sustained a patellar dislocation between 2013 and 2018. Medical records were searched for patient variables including demographics, clinical findings, radiographic findings, treatment, adverse outcomes and military disposition. Patient variables associated with recurrent instability and undergoing medical separation were determined using univariate analysis and multivariate logistic regression. A total of 207 patients met inclusion and exclusion criteria. RESULTS: Following patellar instability event, 30% of the cohort underwent surgical treatment. Fourteen per cent (29 of 207) underwent medical separation from military service. Regardless of treatment, 9% (18 of 207) experienced recurrent dislocation and 3% (6 of 207) experienced recurrent instability without dislocation. On multivariate analysis, none of the studied patient variables were associated with recurrent instability or medical separation. CONCLUSIONS: Among military personnel, return to duty rates are similar to return to sport rates in civilians. This study demonstrates no difference in risk of recurrent instability or medical separation based on anatomical factors, which is useful during shared decision-making regarding treatment options and goals.

Unusual coordination mode for 1,3-diphosphete ligands towards a Cr-Cr quintuple bond complex.

The reaction of LCr5̲CrL (L = N2C25H29, 1) with the phosphaalkynes R-C≡P (R = tBu, Me, Ad) yields the neutral dimerisation compounds [L2Cr2(µ,η1:η1:η2:η2-P2C2R2)] (R = tBu (2), Me (3)) and the tetrahedrane complex [L2Cr2(µ,η2:η2-PCAd)] (4). The 1,3-diphosphete ligands in complexes 2 and 3 are the first to possess this structural feature spanned over a metal-metal multiple bond, while the slightly bigger adamantyl phosphaalkyne remains a monomer in 4 with a side-on coordination mode.

Why are US military personnel prescribed transdermal fentanyl patches?

INTRODUCTION: Transdermal fentanyl is a continuous release opioid delivery system intended for use in opioid-tolerant patients requiring around-the-clock opioid therapy. The purpose of this study is to identify the most common indications for transdermal fentanyl prescriptions in active duty US military personnel, and determine whether these prescriptions meet US Food and Drug Administration (FDA) labelling. METHODS: Active duty US military personnel initiating transdermal fentanyl therapy with prescriptions filled at Military Health System pharmacies between 2015 and 2019 were identified in the Military Data Repository. Electronic health records were searched for patient demographic information, clinical information and prescription data. A total of 225 patients with complete data were identified. RESULTS: The most common reason for transdermal fentanyl initiation was chronic non-cancer musculoskeletal pain. Among patients with non-cancer pain, 36% received their initial prescription from an internal medicine/primary care provider, and 35% did not meet published US FDA criteria for opioid tolerance prior to treatment initiation. There was an 81% decrease in patients initiating therapy between 2015 and 2019. CONCLUSIONS: While a substantial minority of transdermal fentanyl prescriptions to US military personnel did not meet FDA guidelines on appropriate use, the overall number of prescriptions fell dramatically over the study period. This suggests that automated profile review or additional targeted policies to limit transdermal fentanyl prescribing are unnecessary at this time.

The 2020 MELODI workshop on the effects of spatial and temporal variation in dose delivery.

A key activity of MELODI is to organise annual European meetings where scientific results and future directions and strategies of relevant research are discussed. The annual meetings, previously organised solely under the auspices of MELODI are, since 2016, jointly organised by the European platforms and referred to as European Radiation Protection Weeks (ERPW). In addition to ERPW meetings, MELODI organises and finances annual workshops dedicated to specific topics. Outputs and recommendations from the meetings are published as review articles. The 2020 workshop focussed on one of the cross cutting topics: the effects of spatial and temporal variation in dose delivery on disease risk. The current issue of REBS includes five review articles from the workshop on the effects of spatial and temporal variation in dose delivery and this editorial is a short summary of their content.

Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general.

Datasets of in vitro clonogenic assays showing low dose hyper-radiosensitivity and induced radioresistance.

Low dose hyper-radiosensitivity and induced radioresistance are primarily observed in surviving fractions of cell populations exposed to ionizing radiation, plotted as the function of absorbed dose. Several biophysical models have been developed to quantitatively describe these phenomena. However, there is a lack of raw, openly available experimental data to support the development and validation of quantitative models. The aim of this study was to set up a database of experimental data from the public literature. Using Google Scholar search, 46 publications with 101 datasets on the dose-dependence of surviving fractions, with clear evidence of low dose hyper-radiosensitivity, were identified. Surviving fractions, their uncertainties, and the corresponding absorbed doses were digitized from graphs of the publications. The characteristics of the cell line and the irradiation were also recorded, along with the parameters of the linear-quadratic model and/or the induced repair model if they were provided. The database is available in STOREDB, and can be used for meta-analysis, for comparison with new experiments, and for development and validation of biophysical models.

Aerosol Transport Modeling: The Key Link Between Lung Infections of Individuals and Populations.

The recent COVID-19 pandemic has propelled the field of aerosol science to the forefront, particularly the central role of virus-laden respiratory droplets and aerosols. The pandemic has also highlighted the critical need, and value for, an information bridge between epidemiological models (that inform policymakers to develop public health responses) and within-host models (that inform the public and health care providers how individuals develop respiratory infections). Here, we review existing data and models of generation of respiratory droplets and aerosols, their exhalation and inhalation, and the fate of infectious droplet transport and deposition throughout the respiratory tract. We then articulate how aerosol transport modeling can serve as a bridge between and guide calibration of within-host and epidemiological models, forming a comprehensive tool to formulate and test hypotheses about respiratory tract exposure and infection within and between individuals.

Total hip and knee arthroplasty after lower extremity amputation in a military population.

INTRODUCTION: The military includes lower extremity amputees requiring arthroplasty; however, there is little literature on this population. The primary aim of this study was to report demographics and clinical factors in amputees who undergo total hip or knee arthroplasty (THA/TKA) in the Military Health System (MHS). Second, patient-reported outcome measures (PROMs) are reported. METHODS: The Military Data Repository was queried for patients with lower extremity amputations and TKA or THA between 1 October 2014 and 12 October 2020. The medical records were reviewed and patients were contacted to complete PROMs. Mean follow-up for TKA and THA was 5.5 and 2.5 years, respectively. RESULTS: Nineteen TKAs (76%) and eight THAs (28%) were performed in 25 patients. Mean age of TKA and THA patients at the time of arthroplasty was 57 years old. A majority of TKA (68%) and THA (57%) patients underwent amputations secondary to trauma. Nearly all TKAs were performed on the contralateral side to the amputation (95%), while half of THAs were performed on the ipsilateral side (50%). Two THAs (29%) were revised due to periprosthetic fractures, whereas six TKAs (32%) were revised or reoperated on due to infection. Ten TKA patients completed PROMs. The mean score on Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) was 41.8 and Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) was 41.6 (Global Physical Health) and 49.6 (Global Mental Health). CONCLUSIONS: Most TKAs were performed on the contralateral limb, suggesting increased demand on the joint. The most common indication for amputation and post-TKA complication was trauma and infection, respectively. KOOS JR may not accurately capture the outcomes of this population, or they simply do worse. However, PROMIS-10 scores were similar to the non-amputee population, suggesting that the PROMIS-10 may be more useful than the KOOS JR.

Tracing genetic connections of ancient Hungarians to the 6th-14th century populations of the Volga-Ural region.

Most of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological and archaeological data. We present here the uniparental genetic makeup of the mediaeval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originate from ancient proto-Ob-Ugric people from Western Siberia (6th-13th century), the pre-Conquest period and subsisting Hungarians from the Volga-Ural region (6th-14th century) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework. We analyzed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups' genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East Eurasian uniparental lineages in their gene pool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups. Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors' maternal gene pool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.

Ancient genomes reveal origin and rapid trans-Eurasian migration of 7th century Avar elites.

The Avars settled the Carpathian Basin in 567/68 CE, establishing an empire lasting over 200 years. Who they were and where they came from is highly debated. Contemporaries have disagreed about whether they were, as they claimed, the direct successors of the Mongolian Steppe Rouran empire that was destroyed by the Turks in ∼550 CE. Here, we analyze new genome-wide data from 66 pre-Avar and Avar-period Carpathian Basin individuals, including the 8 richest Avar-period burials and further elite sites from Avar's empire core region. Our results provide support for a rapid long-distance trans-Eurasian migration of Avar-period elites. These individuals carried Northeast Asian ancestry matching the profile of preceding Mongolian Steppe populations, particularly a genome available from the Rouran period. Some of the later elite individuals carried an additional non-local ancestry component broadly matching the steppe, which could point to a later migration or reflect greater genetic diversity within the initial migrant population.

Modeling of nursing care-associated airborne transmission of SARS-CoV-2 in a real-world hospital setting.

Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient's activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm2/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens).

From tangled banks to toxic bunnies; a reflection on the issues involved in developing an ecosystem approach for environmental radiation protection.

The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach.

Author Correction: Genetic insights into the social organisation of the Avar period elite in the 7th century AD Carpathian Basin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated aerosol

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the peripheral airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the peripheral airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated aerosol. For this purpose, the Stochastic Lung Deposition Model has been applied. Aerosol size distribution and breathing parameters were taken from the literature supposing normal breathing through the nose. We found that the probability of direct infection of the peripheral airways due to inhalation of aerosol generated by a bystander cough is very low. As the number of pathogens deposited in the extrathoracic airways is {bsim}10 times higher than in the peripheral airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous. The period between the onset of initial symptoms and the potential clinical deterioration could provide an opportunity for prevention of pneumonia by blocking or significantly reducing the transport of viruses towards the peripheral airways. Coughing into a tissue or cloth even at home in order to absorb the emitted aerosol is highly recommended to avoid the continuous re-inhalation of own cough.

A massacre of early Neolithic farmers in the high Pyrenees at Els Trocs, Spain.

Violence seems deeply rooted in human nature and an endemic potential for such is today frequently associated with differing ethnic, religious or socio-economic backgrounds. Ethnic nepotism is believed to be one of the main causes of inter-group violence in multi-ethnic societies. At the site of Els Trocs in the Spanish Pyrenees, rivalling groups of either migrating early farmers or farmers and indigenous hunter-gatherers collided violently around 5300 BCE. This clash apparently resulted in a massacre of the Els Trocs farmers. The overkill reaction was possibly triggered by xenophobia or massive disputes over resources or privileges. In the present, violence and xenophobia are controlled and sanctioned through social codes of conduct and institutions. So that, rather than representing an insurmountable evolutionary inheritance, violence and ethnic nepotism can be overcome and a sustainable future achieved through mutual respect, tolerance and openness to multi-ethnic societies.

Genetic insights into the social organisation of the Avar period elite in the 7th century AD Carpathian Basin.

After 568 AD the Avars settled in the Carpathian Basin and founded the Avar Qaganate that was an important power in Central Europe until the 9th century. Part of the Avar society was probably of Asian origin; however, the localisation of their homeland is hampered by the scarcity of historical and archaeological data. Here, we study mitogenome and Y chromosomal variability of twenty-six individuals, a number of them representing a well-characterised elite group buried at the centre of the Carpathian Basin more than a century after the Avar conquest. The studied group has maternal and paternal genetic affinities to several ancient and modern East-Central Asian populations. The majority of the mitochondrial DNA variability represents Asian haplogroups (C, D, F, M, R, Y and Z). The Y-STR variability of the analysed elite males belongs only to five lineages, three N-Tat with mostly Asian parallels and two Q haplotypes. The homogeneity of the Y chromosomes reveals paternal kinship as a cohesive force in the organisation of the Avar elite strata on both social and territorial level. Our results indicate that the Avar elite arrived in the Carpathian Basin as a group of families, and remained mostly endogamous for several generations after the conquest.

Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated droplets and aerosol particles.

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the acinar airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the acinar airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid to how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated droplets and aerosol particles. For this purpose, the Stochastic Lung Deposition Model has been applied. Particle size distribution, breathing parameters supposing normal breathing through the nose, and viral loads were taken from the literature. We found that the probability of direct infection of the acinar airways due to inhalation of particles emitted by a bystander cough is very low. As the number of viruses deposited in the extrathoracic airways is about 7 times higher than in the acinar airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous. The period between the onset of initial symptoms and the potential clinical deterioration could provide an opportunity for prevention of pneumonia by blocking or significantly reducing the transport of viruses towards the acinar airways. Therefore, even non-specific treatment forms like disinfection of the throat and nasal and oral mucosa may effectively keep the viral load of the upper airways low enough to avoid or prolong the progression of the disease. In addition, using a tissue or cloth in order to absorb droplets and aerosol particles emitted by own coughs of infected patients before re-inhalation is highly recommended even if they are alone in quarantine.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract.

Inhalation of short-lived radon progeny is an important cause of lung cancer. To characterize the absorbed doses in the bronchial region of the airways due to inhaled radon progeny, mostly regional lung deposition models, like the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection, are used. However, in this model the site specificity of radiation burden in the airways due to deposition and fast airway clearance of radon progeny is not described. Therefore, in the present study, the Radact version of the stochastic lung model was used to quantify the cellular radiation dose distribution at airway generation level and to simulate the kinetics of the deposited radon progeny resulting from the moving mucus layer. All simulations were performed assuming an isotope ratio typical for an average dwelling, and breathing mode characteristic of a healthy adult sitting man. The study demonstrates that the cell nuclei receiving high doses are non-uniformly distributed within the bronchial airway generations. The results revealed that the maximum of the radiation burden is at the first few bronchial airway generations of the respiratory tract, where most of the lung carcinomas of former uranium miners were found. Based on the results of the present simulations, it can be stated that regional lung models may not be fully adequate to describe the radiation burden due to radon progeny. A more realistic and precise calculation of the absorbed doses from the decay of radon progeny to the lung requires deposition and clearance to be simulated by realistic models of airway generations.

QUANTITATIVE ANALYSIS OF THE POTENTIAL ROLE OF BASAL CELL HYPERPLASIA IN THE RELATIONSHIP BETWEEN CLONAL EXPANSION AND RADON CONCENTRATION.

Applying the two-stage clonal expansion model to epidemiology of lung cancer among uranium miners, it has been revealed that radon acts as a promoting agent facilitating the clonal expansion of already mutated cells. Clonal expansion rate increases non-linearly by radon concentration showing a plateau above a given exposure rate. The underlying mechanisms remain unclear. Earlier we proposed that progenitor cell hyperplasia may be induced upon chronic radon exposure. The objective of the present study is to test whether the induction of hyperplasia may provide a quantitative explanation for the plateau in clonal expansion rate. For this purpose, computational epithelium models were prepared with different number of basal cells. Cell nucleus hits were computed by an own-developed Monte-Carlo code. Surviving fractions were estimated based on the number of cell nucleus hits. Cell division rate was computed supposing equilibrium between cell death and cell division. It was also supposed that clonal expansion rate is proportional to cell division rate, and therefore the relative increase in cell division rate and clonal expansion rate are the same functions of exposure rate. While the simulation results highly depend on model parameters with high uncertainty, a parameter set has been found resulting in a cell division rate-exposure rate relationship corresponding to the plateau in clonal expansion rate. Due to the high uncertainty of the applied parameters, however, further studies are required to decide whether the induction of hyperplasia is responsible for the non-linear increase in clonal expansion rate or not. Nevertheless, the present study exemplifies how computational modelling can contribute to the integration of observational and experimental radiation protection research.

SURVEY ON DATA MANAGEMENT IN RADIATION PROTECTION RESEARCH.

The importance of datasharing is of increasing concern to funding bodies and institutions. With some prescience, the radiobiology community has established datasharing infrastructures over the last two decades, including STORE; however, the utilization of these databases is disappointing. The aim of the present study was to identify the current state of datasharing amongst researchers in radiation protection, and to identify barriers to effective sharing. An electronic survey was prepared, including questions on post-publication data provision, institutional, funding agency, and journal policies, awareness of datasharing infrastructures, attitudinal barriers and technical support. The survey was sent to the members of a mailing list maintained by the EC funded CONCERT project. Responses identified that the radiation protection community shared similar concerns to other groups canvassed in earlier studies; the perceived negative impact of datasharing on competitiveness, career development and reputation, along with concern about the costs of data management. More surprising was the lack of awareness of existing datasharing platforms. We find that there is a clear need for education and training in data management and for a significant programme of improving awareness of Open Data issues.