Computational ballistic analysis of the cranial shot to John F. Kennedy.

Almost 60 years after the assassination of President John F. Kennedy in 1963, the majority of Americans are still reluctant to believe official reports presented by the commissions gathered in 1964 and again in 1976 that determined the direction of the shot resulting in the fatal head injury. Long-withheld, confidential government files released in 2017 reignited the controversy. The present investigation computationally simulated projectile-skull-impacts from the direction specified in official reports and from three other directions. Detailed geometric models of the human head and ammunition, as well as known parameters from the assassination site served as the supportive base for analysis. Constitutive mathematical models for the impact of projectile material with skull tissues at supersonic speed were employed to analyze bone and bullet fragmentation mechanics. Simulated fracture characteristics of bone and bullet were compared with photographic and X-ray evidence. The most likely origin of the fatal shot was determined based on the degree of corresponding deformation and fragmentation between simulation and documented evidence. Computational corroboration could be established as physically consistent with high-speed impact from the rear, as established by the official commissions. Simulations of three other speculative shot origins did not correspond with the documented evidence.

Perioperative Teaching and Feedback: How are we doing in Canadian OTL-HNS programs?

BACKGROUND: Discrepancies between resident and faculty perceptions regarding optimal teaching and feedback during surgery are well known but these differences have not yet been described in Otolaryngology - Head and Neck Surgery (OTL-HNS). The objectives were thus to compare faculty and resident perceptions of perioperative teaching and feedback in OTL-HNS residency programs across Canada with the aim of highlighting potential areas for improvement. METHODS: An anonymous electronic questionnaire was distributed to residents and teaching faculty in OTL-HNS across Canada with additional paper copies distributed at four institutions. Surveys consisted of ratings on a 5-point Likert scale and open-ended questions. Responses among groups were analysed with the Wilcoxon-Mann Whitney test, while thematic analysis was used for the open-ended questions. RESULTS: A total of 143 teaching faculty and residents responded with statistically significant differences on 11 out of 25 variables. Namely, faculty reported higher rates of pre and intra-operative teaching compared to resident reports. Faculty also felt they gave adequate feedback on residents' strengths and technical skills contrary to what the residents thought. Both groups did agree however that pre-operative discussion is not consistently done, nor is feedback consistently given or sought. CONCLUSION: Faculty and residents in OTL-HNS residency programs disagree on the frequency and optimal timing of peri-operative teaching and feedback. This difference in perception emphasizes the need for a more structured approach to feedback delivery including explicitly stating when feedback is being given, and the overall need for better communication between residents and staff.

Usp9X Regulates Cell Death in Malignant Peripheral Nerve Sheath Tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in neurofibromatosis type 1 (NF1) patients. Current treatment modalities have been largely unsuccessful in improving MPNST patient survival, making the identification of new therapeutic targets urgent. In this study, we found that interference with Usp9X, a deubiquitinating enzyme which is overexpressed in nervous system tumors, or Mcl-1, an anti-apoptotic member of the Bcl-2 family whose degradation is regulated by Usp9X, causes rapid death in human MPNST cell lines. Although both Usp9X and Mcl-1 knockdown elicited some features of apoptosis, broad spectrum caspase inhibition was ineffective in preventing knockdown-induced MPNST cell death suggesting that caspase-independent death pathways were also activated. Ultrastructural examination of MPNST cells following either Usp9X interference or pharmacological inhibition showed extensive cytoplasmic vacuolization and swelling of endoplasmic reticulum (ER) and mitochondria most consistent with paraptotic cell death. Finally, the Usp9X pharmacological inhibitor WP1130 significantly reduced human MPNST growth and induced tumor cell death in an in vivo xenograft model. In total, these findings indicate that Usp9X and Mcl-1 play significant roles in maintaining human MPNST cell viability and that pharmacological inhibition of Usp9X deubiquitinase activity could be a therapeutic target for MPNST treatment.

Factors determining outcome of corrective osteotomy for malunited paediatric forearm fractures: a systematic review and meta-analysis.

The aim of this study was to identify predictors of a superior functional outcome after corrective osteotomy for paediatric malunited radius and both-bone forearm fractures. We performed a systematic review and meta-analysis of individual participant data, searching databases up to 1 October 2016. Our primary outcome was the gain in pronosupination seen after corrective osteotomy. Individual participant data of 11 cohort studies were included, concerning 71 participants with a median age of 11 years at trauma. Corrective osteotomy was performed after a median of 12 months after trauma, leading to a mean gain of 77° in pronosupination after a median follow-up of 29 months. Analysis of variance and multiple regression analysis revealed that predictors of superior functional outcome after corrective osteotomy are: an interval between trauma and corrective osteotomy of less than 1 year, an angular deformity of greater than 20° and the use of three-dimensional computer-assisted techniques. LEVEL OF EVIDENCE: II.

Dairy farmers' perceptions toward the implementation of on-farm Johne's disease prevention and control strategies.

Implementation of specific management strategies on dairy farms is currently the most effective way to reduce the prevalence of Johne's disease (JD), an infectious chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). However, dairy farmers often fail to implement recommended strategies. The objective of this study was to assess perceptions of farmers participating in a JD prevention and control program toward recommended practices, and explore factors that influence whether or not a farmer adopts risk-reducing measures for MAP transmission. Semi-structured interviews were conducted with 25 dairy farmers enrolled in a voluntary JD control program in Alberta, Canada. Principles of classical grounded theory were used for participant selection, interviewing, and data analysis. Additionally, demographic data and MAP infection status were collected and analyzed using quantitative questionnaires and the JD control program database. Farmers' perceptions were distinguished according to 2 main categories: first, their belief in the importance of JD, and second, their belief in recommended JD prevention and control strategies. Based on these categories, farmers were classified into 4 groups: proactivists, disillusionists, deniers, and unconcerned. The first 2 groups believed in the importance of JD, and proactivists and unconcerned believed in proposed JD prevention and control measures. Groups that regarded JD as important had better knowledge about best strategies to reduce MAP transmission and had more JD risk assessments conducted on their farm. Although not quantified, it also appeared that these groups had more JD prevention and control practices in place. However, often JD was not perceived as a problem in the herd and generally farmers did not regard JD control as a "hot topic" in communications with their herd veterinarian and other farmers. Recommendations regarding how to communicate with farmers and motivate various groups of farmers according to their specific perceptions were provided to optimize adoption of JD prevention and control measures and thereby increase success of voluntary JD control programs.

Simulation-based otolaryngology - head and neck surgery boot camp: 'how I do it'.

BACKGROUND: In otolaryngology, surgical emergencies can occur at any time. An annual surgical training camp (or 'boot camp') offers junior residents from across North America the opportunity to learn and practice these skills in a safe environment. The goals of this study were to describe the set-up and execution of a simulation-based otolaryngology boot camp and to determine participants' confidence in performing routine and emergency on-call procedures in stressful situations before and after the boot camp. METHODS: There were three main components of the boot camp: task trainers, simulations and an interactive panel discussion. Surveys were given to participants before and after the boot camp, and their confidence in performing the different tasks was assessed via multiple t-tests. RESULTS: Participants comprised 22 residents from 12 different universities; 10 of these completed both boot camp surveys. Of the nine tasks, the residents reported a significant improvement in confidence levels for six, including surgical airway and orbital haematoma management. CONCLUSION: An otolaryngology boot camp gives residents the chance to learn and practice emergency skills before encountering the emergencies in everyday practice. Their confidence in multiple skillsets was significantly improved after the boot camp. Given the shift towards competency-based learning in medical training, this study has implications for all surgical and procedural specialties.

[Systematic Readability Analysis of Medical Texts on Websites of German University Clinics for General and Abdominal Surgery]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten von Kliniken für Allgemein- und Viszeralchirurgie deutscher Universitätskliniken.

Background: Besides the function as one of the main contact points, websites of hospitals serve as medical information portals. As medical information texts should be understood by any patients independent of the literacy skills and educational level, online texts should have an appropriate structure to ease understandability. Materials and Methods: Patient information texts on websites of clinics for general surgery at German university hospitals (n = 36) were systematically analysed. For 9 different surgical topics representative medical information texts were extracted from each website. Using common readability tools and 5 different readability indices the texts were analysed concerning their readability and structure. The analysis was furthermore stratified in relation to geographical regions in Germany. Results: For the definite analysis the texts of 196 internet websites could be used. On average the texts consisted of 25 sentences and 368 words. The reading analysis tools congruously showed that all texts showed a rather low readability demanding a high literacy level from the readers. Conclusion: Patient information texts on German university hospital websites are difficult to understand for most patients. To fulfill the ambition of informing the general population in an adequate way about medical issues, a revision of most medical texts on websites of German surgical hospitals is recommended.

Long-lived plasma cells are generated in mucosal immune responses and contribute to the bone marrow plasma cell pool in mice.

During systemic immune responses, plasma blasts are generated in secondary lymphoid organs and migrate to the bone marrow, where they can become long-lived, being responsible for the maintenance of long-term antibody titers. Plasma blasts generated in mucosal immune responses of the small intestine home to the lamina propria (LP), producing mainly immunoglobulin A. The migration of these antibody-secreting cells is well characterized during acute immune responses. Less is known about their lifetime and contribution to the long-lived bone marrow compartment. Here we investigate the lifetime of plasma cells (PCs) and the relationship between the PC compartments of the gut and bone marrow after oral immunization. Our findings indicate that PCs in the LP can survive for extended time periods. PCs specific for orally administered antigens can be detected in the bone marrow for at least 9 months after immunization, indicating that the mucosal PC compartment can contribute to the long-lived PC pool in this organ, independent of the participation of splenic B cells. Our findings suggest that the compartmentalization between mucosal and systemic PC pools is less strict than previously thought. This may have implications for the development of vaccines as well as for autoantibody-mediated diseases.

Imaging of a linear diode bar for an optical cell stretcher.

We present a simplified approach for imaging a linear diode bar laser for application as an optical stretcher within a microfluidic geometry. We have recently shown that these linear sources can be used to measure cell mechanical properties; however, the source geometry creates imaging challenges. To minimize intensity losses and simplify implementation within microfluidic systems without the use of expensive objectives, we combine aspheric and cylindrical lenses to create a 1:1 image of the source at the stretcher focal plane and demonstrate effectiveness by measuring the deformation of human red blood cells and neutrophils.

The prevalence of vitamin D deficiency in patients with vertebral fragility fractures.

Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, sd 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, sd 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women.

Liquid dextran does not increase the elution rate of different antibiotics from bone cement.

PURPOSE: To investigate the possibility of increasing elution of fosfomycin, gentamicin, clindamycin, and vancomycin by the addition of dextran fluid during the cement-mixing phase. METHODS: In 12 test series, we produced standardized, antibiotic-loaded test specimens of cement, with and without addition of dextran, and determined their effectiveness against three reference pathogens in agar diffusion and elution tests. RESULTS: In the test series using combined agents, Refobacin(®)-Palacos(®)R plus fosfomycin continuously produced the largest zone of inhibition, both against methicillin-sensitive Staphylococcus aureus (p = 0.009) and against methicillin-resistant Staphylococcus aureus (p = 0.009). The addition of dextran to the various test series had no useful effect on the size of the zone of inhibition for any of the antibiotics tested. CONCLUSIONS: Dextran supplementation in Refobacin(®)-Palacos(®)R bone cement did not have the hope for positive effect on the elution rate of bound antibiotics.

[Systematic analysis of the readability of patient information on the websites of clinics for plastic surgery]. / Systematische Analyse der Lesbarkeit von Patienteninformationen auf den Internetseiten von Kliniken für Plastische Chirurgie.

OBJECTIVE: The Internet is becoming increasing-ly important as a source of information for patients in medical issues. However, many patients have problems to adequately understand texts, especially with medical content. A basic requirement to understand a written text is the read-ability of a text. The aim of the present study was to examine texts on the websites of German -plastic-surgical hospitals with patient information regarding their readability. MATERIALS AND METHODS: In this study, the read-ability of texts of 27 major departments of plastic and Hand surgery in Germany was systematically analysed using 5 recognised readability indices. First, texts were searched based on 20 representative key words and themes. Thereafter, texts were assigned to one of 3 major themes in order to enable statistical analysis. In addition to the 5 readability indices, further objective text parameters were also recorded. RESULTS: Overall, 288 texts were found for analyzation. Most articles were found on the topic of "handsurgery" (n=124), less were found for "facial plastic surgery" (n=80) and "flaps, breast and reconstructive surgery" (n=84). Consistently, all readability indices showed a poor readability for the vast majority of analysed texts with the text appearing readable only for readers with a higher educational level. No significant differences in readability were found between the 3 major themes. CONCLUSION: Especially in the communication of medical information, it is important to consider the knowledge and education of the addressee. The texts studied consistently showed a readability that is understandable only for academics. Thus, a large part of the intended target group is probably not reached. In order to adequately deliver online information material, a revision of the analysed internet texts appears to be recommendable.

[Systematic analysis of the readability of patient information on websites of German nonuniversity ENT hospitals]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten deutscher nichtuniversitärer HNO-Kliniken.

BACKGROUND: Besides their function as one of the main contact points, websites of hospitals serve as medical information portals. All patients should be able to understand medical information texts; regardless of their literacy skills and educational level. Online texts should thus have an appropriate structure to ease their comprehension. MATERIALS AND METHODS: Patient information texts on every German nonuniversity ENT hospital website (n = 125) were systematically analysed. For ten different ENT topics a representative medical information text was extracted from each website. Using objective text parameters and five established readability indices, the texts were analysed in terms of their readability and structure. Furthermore, we stratified the analysis in relation to the hospital organisation system and geographical region in Germany. RESULTS: Texts from 142 internet sites could be used for the definite analysis. On average, texts consisted of 15 sentences and 237 words. Readability indices congruously showed that the analysed texts could generally only be understood by a well-educated or even academic reader. CONCLUSION: The majority of patient information texts on German hospital websites are difficult to understand for most patients. In order to fulfil their goal of adequately informing the general population about disease, therapeutic options and the particular focal points of the clinic, a revision of most medical texts on the websites of German ENT hospitals is recommended.

[Epidural injection shows no advantages over oral medication and physiotherapy in the treatment of sciatica, irrespective of the duration of symptoms]. / Kein Vorteil der epiduralen Injektion vs. oraler Medikation und Physiotherapie bei Ischialgie, unabhängig von der Beschwerdedauer.

BACKGROUND: The study presented here investigated the short-term effectiveness of one-off lumbar caudal epidural injection (EI) in sciatica in relationship to the reported duration of pain. MATERIALS AND METHODS: This retrospective analysis involved 106 consecutive in-patients who received either conservative treatment (Group I) or an additional EI on the first day of their treatment (Group II). Both groups were divided according to the duration of symptoms at the time of admission (less than three months, or more than six months). Propensity score matching was performed for the whole collective and the resulting subgroups. This incorporated gender, age and pain intensity at the time of admission. The target parameter were changes on a visual analogue scale (VAS) of pain intensity on days D1, D3, and D10 depending on the respective treatment. A routine evaluation of the mental variables anxiety, depression and somatisation was performed as part of the examination upon admission and their relationship to the success of treatment was later assessed. RESULTS: The mean age of the patients was 61.7 (± 11.6) in Group I and 63.6 (± 13.6) in Group II. 59 % of the patients were female (n = 63). The Lasègue sign was prevalent in 45 % of Group I and 51 % of Group II. The intensity of pain on the day of admission was similar in both groups (7.0 ± 1.0 for Group I, 6.7 ± 1.8 for Group II). The length of stay on the ward was also similar in both groups (10.2 ± 3.9 and 9.4 ± 3.7 d, respectively). It was found that, independent of the duration of symptoms, injection treatment was significantly more effective than conservative treatment only in the early stages (D1 and D3, p < 0.001). No differences could be found in the expression of these mental variables between treatment groups, as these factors showed no influence on the results of therapy. CONCLUSIONS: In the context of acute treatment a once only lumbar caudal epidural injection represents at most a short-term effectiveness for the therapy of sciatica. The results presented here indicate that neither the duration of symptoms nor the measured psychometric variables show any effect on the success of therapy.

Risk factors for heterotopic ossification and spur formation after total knee arthroplasty.

INTRODUCTION: The present study investigated the incidence and risk factors of heterotopic ossification (HO) after implantation of knee prosthesis. MATERIALS AND METHODS: We undertook a retrospective cohort study in 434 cases (363 patients) treated with a total knee replant using a Press-Fit-Condylar (P.F.C.(®)Sigma(®)) prosthesis. The occurrence of HO in radiograph after a follow-up period of 11.2 ± 2.4 months was correlated in a regression model with a variety of influencing factors. RESULTS: 21 patients (4.8 %) developed heterotopic ossifications, all located in the area of the distal femur. The only risk factor found concerning the development of HO was osteoarthritis when compared to rheumatoid arthritis (OR = 4.07, 95 % CI 1.18-14.05; p = 0.0201) and postoperative wound healing problems (OR = 11.32, 95 % CI 3.26-39.33; p = 0.0001). Notching (OR = 2.22, 95 % CI 0.92-5.36; p = 0.0765) and osteophyte forming (hypertrophic) arthrosis (OR = 2.40, 95 % CI 0.97-5.95; p = 0.0596), however, were associated with the development of a bony spur in the contact area of the femoral component of the prosthesis. CONCLUSIONS: Our study has revealed that patients with rheumatoid arthritis are at lower risk of HO than patients with osteoarthritis. An impairment of wound healing would appear to promote the development of a HO. Notching and hypertrophic arthrosis are highly likely to be associated with the development of a bony spur in the ventral contact area of the prosthesis.

[Readability of medical texts on websites of German ENT university hospitals]. / Lesbarkeit von medizinischen Texten im Internetangebot deutscher HNO-Universitätskliniken.

BACKGROUND: A certain proportion of the population has limited literacy skills; therefore, it is important that any patient information published on the internet is readable to the majority of patients for whom the information is intended. MATERIALS AND METHODS: Texts for 10 representative ear nose and throat (ENT) topics were extracted from each website of the 36 German ENT university hospitals. The texts were systematically analyzed by use of the German version of the Flesch ease of reading index. The texts of two topics were additionally analyzed with four more readability tools for the German language. Texts were analyzed in relation to the topic and to the geographical region. RESULTS: On average the texts of 185 websites consisted of 34 sentences and 401 words. Comparably, texts on cochlear implants showed the best readability scores and texts on middle ear pathology the worst. The results of the reading ease index and of the other reading analysis tools showed that all texts require a relatively high literacy level. CONCLUSIONS: To fulfil the ambition of informing the general population about medical issues in an adequate way, a revision of most medical texts on websites of German ENT departments at university hospitals is recommended.

Delayed but effective induction of mucosal memory immune responses against genital HSV-2 in the absence of secondary lymphoid organs.

To examine whether local immunization in the absence of secondary lymphoid organs (SLOs) could establish effective antiviral memory responses in the female genital tract, we examined immunity in the vaginal tracts of LTα-/- mice, LTα-/- SPL (splenectomized), and control C57BL/6 (WT) mice. All three groups of mice were immunized intravaginally (IVAG) with attenuated thymidine kinase-negative (TK(-)) Herpes simplex virus type 2 (HSV-2) and challenged 4-6 weeks later with wild-type (WT) HSV-2. Both groups of LTα-/- mice exhibited delayed viral clearance and prolonged genital pathology after immunization. Following IVAG WT HSV-2 challenge, LTα-/- and LTα-/- SPL mice had significantly lower levels of HSV-2-specific IgG and IgA in the vaginal secretions. Although the frequency of B and T cells in the vaginal mucosa was comparable or higher in both groups of LTα-/- mice, lower frequency of HSV-2-specific interferon-γ (IFNγ)-producing CD3+ T cells was seen after immunization and after challenge, compared with WT group. Despite this, immunized mice in all three groups showed complete sterile protection against IVAG WT HSV-2 challenge. These results show that even in the absence of SLOs, IVAG immunization generates effector memory immune responses at genital mucosa that can provide antiviral protection against subsequent viral exposures. This will inform new strategies to design mucosal vaccines against sexually transmitted infections.

Against all odds: a qualitative study of rehabilitation of persons with spinal cord injury in Afghanistan.

STUDY DESIGN: Cross-sectional, survey. OBJECTIVES: To describe the challenges in rehabilitating patients with spinal cord injury in the orthopaedic centres of the International Committee of the Red Cross in Afghanistan. SETTING: Afghanistan (Kabul, Herat, Mazar-i-Sharif, Jalalabad, Gulbahar), April 2012. METHODS: Semi-structured interviews were conducted with managers and professional staff of ICRC and other concerned organizations/institutions (Ministries, hospitals, non-governmental organizations), and with people with SCI and their families. Quantitative data were extracted from routine statistics. RESULTS: A reported annual incidence of roughly 21 SCI cases per million in Afghanistan could be established for the year 2011. Acts of violence were the most frequent cause, followed by spinal tuberculosis. Despite very elementary prehospital and hospital care, SCI individuals are rehabilitated within the limits set by available technology and socio-economic factors. Support to community reintegration is effective for the ones living within a radius determined by distance and security. CONCLUSION: Rehabilitation of SCI patients would be ineffective without covering at least part of the services usually provided during the phases of acute hospital care and community reintegration. The question of whether services currently provided by foreign-based or funded organizations can be extended into a potential postconflict period, and by whom, remains open.

Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer: a phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium.

BACKGROUND: Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC). METHODS: Chemotherapy-naïve patients with metastatic CRPC received sagopilone (one cycle: 16 mg m(-2) intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (≥50% PSA reduction confirmed ≥28 days apart). According to the Simon two-stage design, ≥3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available. RESULTS: In all, 53 patients received ≥2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m(-2) during initial six cycles, mean dose intensity 94±9%. The confirmed PSA response rate was 37%. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and pain in the extremities (47.2%). Sagopilone was associated with very little haematological toxicity. CONCLUSION: This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-naïve CRPC.