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Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a Staphylococcus epidermidis Kirschner wire-based prosthesis rat model. We used 52 male Sprague–Dawley rats in four groups: negative controls (no phage, sterile implant), PJI controls (bacteria, no phage), sterile phage (phages given, sterile implant), and PJI (bacteria, phages given). The PJI groups were inoculated with ~106 CFU of S. epidermidis. The groups receiving phage were intra-articularly injected with ~108 PFU of vB_SepM_Alex five days post-implantation. The rats were euthanized between 30 min and 48 h post-injection. The measured phage concentrations between the PJI rats and the sterile controls in periarticular tissues were not significantly different. In a noncompartmental pharmacokinetic analysis, the estimated phage half-lives were under 6 h (combined: 3.73 [IQR, 1.45, 10.07]). The maximum phage concentrations were reached within 2 h after administration (combined: 0.75 [0.50, 1.75]). The estimated phage mean residence time was approximately three hours (combined: 3.04 [1.44, 4.19]). Our study provides a preliminary set of pharmacokinetic parameters that can inform future phage dosing studies and animal models of phage therapy for PJIs.

Background and Objectives: Despite the promise of phage therapy (PT), its efficacy in prosthetic joint infection (PJI) management is unknown. Much of the current literature is largely limited to case reports and series. Materials and Methods: In order to help inform power calculations for future clinical trials and comparative analyses, we performed a systematic review and proportional meta-analysis of early PT outcomes to provide a preliminary assessment of early phage therapy treatment outcomes for cases of PJI. Results: In a search of available literature across MEDLINE (Ovid, Wolters Kluwer, Alphen aan den Rijn, The Netherlands), Embase (Elsevier, Amsterdam, The Netherlands), the Web of Science Core Collection (Clarivate, London, UK), and Cochrane Central (Wiley, Hoboken, NJ, USA) up to 23 September 2023, we identified 37 patients with PJIs receiving adjunctive PT. Patients most frequently reported Staphylococcal species infection (95%) and intraarticular phage delivery (73%). Phage cocktail (65%) and antibiotic co-administration (97%) were common. A random-effects proportional meta-analysis suggested infection remission in 78% of patients (95% CI: 39%, 95%) (I2 = 55%, p = 0.08) and 83% with a minimum 12-month follow-up (95% CI: 53%, 95%) (I2 = 26%, p = 0.26). Conclusions: Our study provides a preliminary estimate of PT’s efficacy in PJIs and informs future comparative studies.

Background:. Extensive research collaborations exist between researchers from high-income countries (HICs) and those from low-income countries (LICs) and lower-middle-income countries (LMICs). Previous research has suggested that authors from LICs and LMICs are underrepresented as first and last authors in the orthopaedic literature on local populations, particularly in LICs. We present a bibliometric analysis of authorship solely in studies published in orthopaedic journals that are based in LICs and LMICs. Methods:. The Global Index Medicus was queried, and all articles published from January 1, 2010, to December 31, 2021, in journals with a focus on orthopaedic surgery that were based in an LIC or an LMIC were included. Logistic regressions were calculated to assess the predictors of local authorship. Results:. Over 92% of studies included in our analysis had first or last authors from LICs or LMICs. In terms of study type, the majority (89%) of studies were clinical, although largely of low-level evidence (78% of clinical studies were case reports, case series, or descriptive studies). None received funding. LIC or LMIC first authorship and last authorship were less likely for most types of nonclinical studies. LIC or LMIC first authorship was more likely when there were more study authors. LIC or LMIC first authorship and last authorship were less likely when there were more countries affiliated with the study authors. Finally, when compared with studies with only LIC or LMIC authors, those with a combination of HIC and LIC or LMIC authors had significantly lower rates of LIC or LMIC first authorship (93.3% versus 62.5%) and last authorship (97.7% versus 70.8%). Conclusions:. Our study presents one of the first analyses to assess authorship patterns in the orthopaedic literature of locally published journals in LICs and LMICs. Future studies are needed to contextualize our findings within a broader bibliometric landscape in order to better address the ongoing challenges to building research capacity in LICs and LMICs. Clinical Relevance:. Our study highlights important observations regarding authorship in international, collaborative research in orthopaedics.

We present an analysis of eight JWST Mid-Infrared Instrument (MIRI) 5.6 μ m images with 5 σ depths of ≈0.1 μ Jy. We detect 2854 sources within our combined area of 18.4 arcmin ^2 . We compute the MIRI 5.6 μ m number counts, including an analysis of the field-to-field variation. Compared to earlier published MIRI 5.6 μ m counts, our counts have a more pronounced knee, at roughly 2 μ Jy. The location and amplitude of the counts at the knee are consistent with the Cowley et al. model predictions, although these models tend to overpredict the counts below the knee. In areas of overlap, 84% of the MIRI sources have a counterpart in the COSMOS2020 catalog. These MIRI sources have redshifts that are mostly in the z ∼ 0.5–2, with a tail out to z ∼ 5. They are predominantly moderate to low stellar masses (10 ^8 –10 ^10 M _⊙ ) main-sequence star-forming galaxies, suggesting that with ≈2 hr exposures, MIRI can reach well below M _* at cosmic noon and reach higher mass systems out to z ∼ 5. Nearly 70% of the COSMOS2020 sources in areas of overlap now have a data point at 5.6 μ m (rest-frame near-IR at cosmic noon), which allows for more accurate stellar population parameter estimates. Finally, we discovered 31 MIRI-bright sources not present in COSMOS2020. A crossmatch with IRAC channel 1 suggests that 10%–20% of these are likely lower mass ( M _* ≈ 10 ^9 M _⊙ ), z ∼ 1 dusty galaxies. The rest (80%–90%) are consistent with more massive but still very dusty galaxies at z > 3.

The Balmer decrement (H α /H β ) provides a constraint on attenuation, the cumulative effects of dust grains in the ISM. The ratio is a reliable spectroscopic tool for deriving the dust properties of galaxies that determine many different quantities such as star formation rate, metallicity, and SED models. Here, we measure independently both the attenuation and H α /H β of an occulting galaxy pair: VV 191. Attenuation measurements in the visible spectrum ( A _V _,stars ) from dust maps derived from the F606W filter of HST and the F090W filter of JWST are matched with spaxel-by-spaxel H α /H β observations from the George and Cynthia Mitchell Spectrograph of the McDonald Observatory. The 0.5–0.7 μ m bandpass covers the Balmer lines for VV 191. The dust maps of JWST and HST provide the high sensitivity necessary for comparisons and tracking trends of the geometrically favorable galaxy. We present maps and plots of the Balmer lines for the VV 191 galaxy pair and for a specific region highlighting dust lanes for VV 191b in the overlap region. We compute A _V _,H _II from H α /H β and plot both quantities against A _V _,stars . Our results show that regions with higher dust content, residing closer to the spiral center, dominate ionized gas attenuation, leading to an overestimation of A _V _,H _II by a factor of 2. Further out in the spiral arms, the lower dust content leads to more agreement between the attenuations, indicating a lower star formation rate and larger contribution from older stars to the stellar continuum outside the Petrosian radius.

We present JWST Mid-InfraRed Instrument/Medium-Resolution Spectrometer (MIRI/MRS) observations of an infrared luminous disk galaxy, FLS1, at z ∼ 0.54. With a lookback time of 5 Gyr, FLS1 is chronologically at the midpoint between the peak epoch of star formation and the present day. The MRS data provide maps of the atomic fine structure lines [Ar ii ]6.99, [Ar iii ]8.99, [Ne ii ]12.81, and [Ne iii ]15.55 μ m, polycyclic aromatic hydrocarbon (PAH) features at 3.3, 6.2, and 11.3 μ m, and the warm molecular gas indicators H _2 S(5) and H _2 S(3); all these emission features are spatially resolved. We find that the PAH emission is more extended along the northern side of the galaxy when compared to the well-studied star formation tracer [Ne ii ]. The H _2 rotational lines, which are shock indicators, are strongest and most extended on the southern side of the galaxy. [Ar ii ] is the second brightest fine structure line detected in FLS1 and we show that it is a useful kinematic probe that can be detected with JWST out to z ∼ 3. Velocity maps of [Ar ii ] show a rotating disk with signs of turbulence. Our results provide an example of how spatially resolved mid-infrared spectroscopy can allow us to better understand the star formation and interstellar medium conditions in a galaxy halfway back to the peak epoch of galaxy evolution.

BackgroundPrisoners generally have a higher prevalence of HIV infection compared to the general population from which they come. Whether this higher prevalence reflects a higher HIV prevalence in those entering prisons or intramural transmission of HIV within prisons or both is unclear. Any of these possibilities would increase the prevalence found in resident prisoners above that in the general population. Moreover, comparisons of HIV prevalence in entrants and residents and in men and women in African prisons are not well documented. The purpose of this study was to estimate and compare the prevalence and risk factors for HIV infection amongst both male as well as female and entrant and resident prisoners in a large Ethiopian Federal Prison.MethodsWe studied consenting prisoners cross-sectionally from August 2014 through November 2016. Prison entrants were screened continuously for HIV infection and its associated risk factors and residents were screened in two waves one year apart. HIV was diagnosed at the prison hospital laboratory based on the Ethiopian national HIV rapid antibody testing protocol. An external, internationally-accredited reference laboratory confirmed results. Agreement of results between the laboratories were assessed.ResultsA total of 10,778 participants were screened for HIV. Most participants were young (median age of 26 years, IQR: 21-33), male (84%), single (61%), literate (89%), and urban residents (91%) without prior incarceration (96%). Prevalence of HIV was 3.4% overall. Rates of HIV (p = 0.80) were similar in residents and entrants in wave 1 and in entrants in both waves, but were 1.9-fold higher (5.4% vs 2.8%) in residents than entrants in wave 2 (both pConclusionsPrevalence of HIV in the residents at this large, central Ethiopian prison was higher than that estimated for the general population and lower than in many other studies from other smaller Ethiopian prisons. A higher prevalence in residents than in entrants were found only in our second wave of screening after one year of continuous screening and treatment, possibly representing increased willingness of residents at increased risk of HIV to participate in the second wave. Thus, this findings did not clearly support intramural transmission of HIV or the effectiveness of screening to reduce prevalence. Finally, the higher HIV prevalence in women than men requires that they be similarly screened and treated for HIV infection.

Background The ophthalmology residency match is highly competitive, and fourth-year medical students frequently complete away rotations at other institutions hoping to increase their chances of matching. Objective The study aimed to determine the impact of away rotations on the ophthalmology residency selection process and to provide recommendations to faculty for counseling fourth-year medical students as they prepare for the ophthalmology match. Methods A survey was sent in June 2020 to program directors (PDs), medical student educators (MSEs), and residents at 119 accredited ophthalmology residency programs via the Association of University Professors of Ophthalmology e-mail listserv. The 43 PDs and 38 MSEs who responded were asked questions about their views regarding away rotations and visiting students during the residency selection process. The 83 resident respondents were asked about their interview and match success after completing away rotations. Categorical variables were analyzed by Chi-square test. Results The majority of PDs and MSEs typically recommend that fourth-year medical students complete away rotations (p = 0.022 and p = 0.194, respectively). The majority believe that an away rotation will increase the chance of the applicant matching with the host institution (p = 0.004 and p = 0.001, respectively). The vast majority of PDs were more likely to offer an interview to a visiting student compared with another equally qualified applicant (p

Background The fundus examination is an essential part of any ophthalmologic evaluation. However, medical students and primary care physicians often lack confidence with direct ophthalmoscopy. Virtual reality simulators are being employed in medical education to teach this technically challenging examination. Objective To compare medical student ratings of the Eyesi Direct Ophthalmoscope Simulator and traditional small group teaching methods for learning direct ophthalmoscopy skills. Methods All medical students at Indiana University School of Medicine traditionally learn direct ophthalmoscopy in their first 2 years during a small group session led by a physician instructor. Students who later enrolled in ophthalmology clinical electives during 2019 and 2020 were invited to additionally complete the Eyesi Direct Ophthalmoscope Simulator virtual reality curriculum. A voluntary, anonymous survey was sent between June and August 2020 to students who had completed both the traditional and Eyesi simulator sessions. Students were asked to rate their confidence in performing direct ophthalmoscopy following each session, and to indicate which teaching method was superior and why. Chi-square analysis was used to compare categorical variables. Results Students' confidence ratings for performing direct ophthalmoscopy were significantly higher following completion of the Eyesi simulator session compared with the traditional small group session (p

Background:. Online patient information (OPI) plays an important role in pediatric orthopaedic patient/caregiver education and decision-making. We assessed the availability and readability of OPI about osteosarcoma found at pediatric hospital and U.S. National Cancer Institute-designated cancer center (NCIDCC) websites. Methods:. The websites of all NCIDCCs and the top 50 pediatric hospitals identified using U.S. News & World Report were included. The names of NCIDCCs and pediatric hospitals along with the terms “osteosarcoma,” “bone sarcoma,” and “sarcoma” were entered into Google.com, and were classified according to the availability of osteosarcoma-specific web pages. Unpaid monthly visits were assessed using the Ahrefs.com Organic Traffic Score (OTS) metric. Readability was assessed using 5 validated metrics and the composite grade level (CGL), the rounded mean of the 5 metrics. Results:. Of the 71 NCIDCCs and 50 pediatric hospitals, 48 (67.6%) and 18 (36.0%), respectively, did not have at least 1 web page dedicated to osteosarcoma-specific OPI. The mean OTS for all 116 NCIDCC and pediatric hospital osteosarcoma-specific web pages assessed was 177 estimated visits per month, which was less than the mean OTS for the top 10 Google.com “osteosarcoma” search results (3,287.9; p < 0.001). The 52 NCIDCC web pages with osteosarcoma OPI (representing 23 centers) had an average CGL of 12.9, representing a readability level of at least a high school degree. The mean CGL for the 64 pediatric hospital web pages with osteosarcoma OPI (representing 32 hospitals) was 12.8, also representing readability of at least a high school degree. Only 8 (12.5%) of the 64 web pages were written at a seventh or eighth-grade level. Conclusions:. Taken together, the majority of NCIDCCs and pediatric hospitals did not have a dedicated page of OPI for osteosarcoma. Of those that did, NCIDCC and pediatric hospital sites were visited much less frequently than sites visited through the most common Google.com searches. None of the osteosarcoma web pages offering OPI from NCIDCCs and pediatric hospitals met the American Medical Association readability recommendation (sixth-grade reading level). Therefore, greater effort must be made to create and direct patients and parents toward high-quality OPI of the appropriate level. Clinical Relevance:. The clinical relevance of this study lies in its evaluation of OPI and its ability to impact the patient experience of clinical care.

Responses to the Belt and Road Initiative (BRI) have been mixed. Many commentators have welcomed the opportunity for infrastructure development and projects to build economic, political and social connectivity across the region. Others have been openly critical or slow to formulate a clear position. In general, advanced economies have responded less positively than developing economies. This paper employs a constructivist approach to interpret responses to the BRI in advanced economies through analysis of commentary in the United States, the European Union, Japan, Australia and New Zealand. It identifies a diversity of responses within and among these economies and a strong ideational coherence in the frameworks used to assess the BRI. It is concluded that the reception of Chinese-promoted concepts in international affairs, like the BRI, remains challenging due to the dominance of liberal and realist assessments and the accompanying political values. This suggests a need for greater intellectual engagement and more substantial feedback between China and the advanced economies, so as to open the way for a long overdue regional conversation on how development is conceptualized and co-created in a region with diverse approaches to regional economic policy.

BackgroundPulmonary Tuberculosis (PTB) is a major health problem in prisons. Multiple studies of TB in regional Ethiopian prisons have assessed prevalence and risk factors but have not examined recently implemented screening programs for TB in prisons. This study compares bacteriologically-confirmed PTB (BC-PTB) prevalence in prison entrants versus residents and identifies risk factors for PTB in Kality prison, a large federal Ethiopian prison located in Addis Ababa, through a study of an enhanced TB screening program.MethodsParticipating prisoners (n = 13,803) consisted of 8,228 entrants screened continuously and 5,575 residents screened in two cross-sectional waves for PTB symptoms, demographics, TB risk factors, and medical history. Participants reporting at least one symptom of PTB were asked to produce sputum which was examined by microscopy for acid-fast bacilli, Xpert MTB/RIF assay and MGIT liquid culture. Prevalence of BC-PTB, defined as evidence of Mycobacterium tuberculosis (MTB) in sputum by the above methods, was compared in entrants and residents for the study. Descriptive analysis of prevalence was followed by bivariate and multivariate analyses of risk factors.ResultsPrisoners were mainly male (86%), young (median age 26 years) and literate (89%). Prevalence of TB symptoms by screening was 17% (2,334/13,803) with rates in residents >5-fold higher than entrants. Prevalence of BC-PTB detected by screening in participating prisoners was 0.16% (22/13,803). Prevalence in residents increased in the second resident screening compared to the first (R1 = 0.10% and R2 = 0.39%, p = 0.027), but remained higher than in entrants (4.3-fold higher during R1 and 3.1-fold higher during R2). Drug resistance (DR) was found in 38% (5/13) of culture-isolated MTB. Risk factors including being ever diagnosed with TB, history of TB contact and low Body Mass Index (BMI) (ConclusionsBC-PTB prevalence was strikingly lower than previously reported from other Ethiopian prisons. PTB appears to be transmitted within this prison based on its higher prevalence in residents than in entrants. Whether a sustained program of PTB screening of entrants and/or residents reduces prevalence of PTB in prisons is not clear from this study, but our findings suggest that resources should be prioritized to resident, rather than entrant, screening due to higher BC-PTB prevalence. Detection of multi- and mono-DR TB in both entrant and resident prisoners warrants regular screening for active TB and adoption of methods to detect drug resistance.

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios.

Background: Surgical site complications (SSCs) are an important source of morbidity after kidney transplantation. We assessed the incidence, risk factors, outcomes and economic impact of SSCs in a large, diverse population of kidney transplant recipients. Methods: We conducted a single-centre, observational cohort study of adult (age [greater than or equal to] 18 yr) patients who underwent kidney transplantation between Jan. 1, 2005, and Dec. 31, 2015, with a minimum of 1 year of follow-up. Cases of SSC, including infections and wound dehiscence, were determined from patient records. Inpatient and outpatient hospital costs were determined 6 and 12 months after transplantation. We used the Kaplan-Meier product-limit method to determine the cumulative probability of SSCs and other outcomes. We evaluated risk factors and clinical outcomes using Cox proportional hazard ratios. Linear regression models were used to study the effect of SSCs on graft function. Results: The incidence rate of SSCs within 30 days after transplantation was 4.19 per 100 person-months. The cumulative probability of developing an SSC within 30 days after transplantation was 4.13% (95% confidence interval [CI] 3.23%-5.28%). Increased recipient body mass index (BMI) (hazard ratio [HR] 1.07, 95% CI 1.02-1.11), longer cold ischemic time (HR 1.05, 95% CI 1.01-1.09) and transplantation in 2010-2012 versus 2005-2009 (HR 2.20, 95% CI 1.19-4.04) were risk factors for SSC development. In multivariable stepwise Cox proportional hazard models, SSC was a significant risk factor for death-censored graft failure (HR 3.08, 95% CI 1.60-5.90) and total graft failure (HR 2.09, 95% CI 1.32-3.32). Cumulative median hospital costs were $22 38.46 greater for patients with an SSC than for those without. Conclusion: Increased BMI, longer cold ischemic time and the 2010-2012 transplantation period predisposed to SSCs. The development of SSCs was associated with a higher risk of graft failure. Strategies to minimize SSCs may improve outcomes after kidney transplantation and reduce costs. Contexte : Les complications affectant le site opératoire (CSO) sont une importante cause de morbidité après la transplantation rénale. Nous avons évalué l'incidence, les facteurs de risque, les résultats et l'impact économique des CSO auprès d'une volumineuse population hétérogène de receveurs de transplantations rénales. Méthodes : Nous avons procédé à une étude de cohorte d'observation monocentrique regroupant des patients adultes (âge [greater than or equal to] 18 ans) soumis à une transplantation rénale entre le 1er janvier 2005 et le 31 décembre 2015, et suivis pendant au moins 1 an. Les cas de CSO, incluant les infections et les déhiscences de plaies ont été confirmés à partir des dossiers des patients. Le coût des hospitalisations et des soins ambulatoires a été calculé 6 et 12 mois après la transplantation. Nous avons utilisé l'estimateur de produit-limite de Kaplan-Meier pour établir la probabilité cumulative de CSO et d'autres paramètres. Nous avons évalué les facteurs de risque et les paramètres cliniques par la méthode des risques proportionnels de Cox. Des modèles de régression linéaire ont servi à l'analyse de l'impact des CSO sur le fonctionnement des greffons. Résultats : Le taux d'incidence des CSO dans les 30 jours suivant la transplantation a été de 4,19 par 100 mois-personnes. La probabilité cumulative d'une CSO dans les 30 jours suivant la transplantation a été de 4,13% (intervalle de confiance [IC] de 95% 3,23%-5,28%). Les facteurs de risque de CSO étaient indice de masse corporelle (IMC) élevé (risque relatif [RR] 1,07, IC de 95% 1,02-1,11), durée plus longue de l'ischémie froide (RR 1,05, IC de 95% 1,01-1,09) et transplantation effectuée en 2010-2012 c. 2005-2009 (RR 2,20, IC de 95% 1,19-4,04). Dans les modèles à risques proportionnels de Cox multivariés séquentiels, les CSO ont été d'importants facteurs de risque d'échec du greffon après censure des décès survenus avec des greffons fonctionnels (RR 3,08, IC de 95% 1,60-5,90) et d'échec total du greffon (RR 2,09, IC de 95% 1,32-3,32). Les coûts hospitaliers médians cumulatifs ont été de 2238,46 $ de plus chez les patients ayant connu une CSO par rapport aux patients indemnes de CSO. Conclusion : Un IMC élevé, une durée plus longue de l'ischémie froide et la transplantation effectuée entre 2010 et 2012 ont prédisposé les patients à des CSO. Les CSO ont été associées à un risque plus grand d'échec du greffon. Les stratégies visant à prévenir les CSO pourraient améliorer les résultats de la transplantation rénale et en réduire les coûts., Kidney transplantation is the preferred treatment for end-stage renal disease, offering enhanced survival and quality of life as compared to dialysis. However, surgical site complications (SSCs) represent an important source [...]