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Motivation: Data is increasingly used for improvement and research in public health, especially administrative data such as that collected in electronic health records. Patients enter and exit these typically open-cohort datasets non-uniformly; this can render simple questions about incidence and prevalence time-consuming and with unnecessary variation between analyses. We therefore developed methods to automate analysis of incidence and prevalence in open cohort datasets, to improve transparency, productivity and reproducibility of analyses., Implementation: We provide both a code-free set of rules for incidence and prevalence that can be applied to any open cohort, and a python Command Line Interface implementation of these rules requiring python 3.9 or later., General Features: The Command Line Interface is used to calculate incidence and point prevalence time series from open cohort data. The ruleset can be used in developing other implementations or can be rearranged to form other analytical questions such as period prevalence., Availability: The command line interface is freely available from https://github.com/THINKINGGroup/analogy_publication ., (© 2024. The Author(s).)

Deep convection in the Asian summer monsoon is a significant transport process for lifting pollutants from the planetary boundary layer to the tropopause level. This process enables efficient injection into the stratosphere of reactive species such as chlorinated very-short-lived substances (Cl-VSLSs) that deplete ozone. Past studies of convective transport associated with the Asian summer monsoon have focused mostly on the south Asian summer monsoon. Airborne observations reported in this work identify the East Asian summer monsoon convection as an effective transport pathway that carried record-breaking levels of ozone-depleting Cl-VSLSs (mean organic chlorine from these VSLSs ~500 ppt) to the base of the stratosphere. These unique observations show total organic chlorine from VSLSs in the lower stratosphere over the Asian monsoon tropopause to be more than twice that previously reported over the tropical tropopause. Considering the recently observed increase in Cl-VSLS emissions and the ongoing strengthening of the East Asian summer monsoon under global warming, our results highlight that a reevaluation of the contribution of Cl-VSLS injection via the Asian monsoon to the total stratospheric chlorine budget is warranted., Competing Interests: Competing interests statement:The authors declare no competing interest.

The primary goal of medical care during the pre-antiretroviral therapy (ART) era was to keep persons living with human immunodeficiency virus (HIV) alive, whereas since the advent of ART, the treatment objective has shifted to decreasing viral loads and infectiousness while increasing CD4+ T-cell counts and longevity. The health crisis, however, is in preventing and managing multimorbidity (ie, type 2 diabetes), which develops at a more accelerated or accentuated pace among aging persons living with HIV. Relative to the general population and age-matched uninfected adults, it may be more difficult for aging HIV-positive persons who also suffer from multimorbidity to improve negative lifestyle factors to the extent that their behaviors could support the prevention and management of diseases. With recommendations and a viable solution, this article explores the impact of negative lifestyle factors (ie, poor mental health, suboptimal nutrition, physical inactivity, alcohol use) on the health of aging individuals living with HIV., 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.

Background: Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk., Methods: A UK retrospective cohort study (1995-2021) using data from a nationwide database (The Health Improvement Network). Women aged 18-40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls., Results: During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00-1.19), IHD 1.18 (1.01-1.37), cerebrovascular disease 1.04 (0.92-1.17), HF 1.30 (1.02-1.65), hypertension 1.07 (1.03-1.11), T2DM 1.37 (1.29-1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02-1.52), IHD 1.13 (0.81-1.57), cerebrovascular disease 1.43 (1.10-1.87), HF 0.99 (0.57-1.75), hypertension 1.31 (1.21-1.43), T2DM 1.74 (1.52-1.98)., Conclusions: History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health., (© 2023. The Author(s).)

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing., Competing Interests: Competing interests: MDC is the inventor on a patent held by the Secretary of State for Health (UK Government) EP2788503, which covers some of the genetic sequences used in this study. VN is a founder, Director and shareholder in Cambridge Infection Diagnostics Ltd (CID Ltd) which is a commercial company aimed at developing molecular diagnostics in infection and antimicrobial and AMR stewardship. NMB, GD and ACM are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd (CID Ltd). All other authors declare no conflict of interest., (Copyright: © 2022 Navapurkar V et al.)

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing., Competing Interests: Competing interests: MDC is the inventor on a patent held by the Secretary of State for Health (UK Government) EP2788503, which covers some of the genetic sequences used in this study. VN is a founder, Director and shareholder in Cambridge Infection Diagnostics Ltd (CID Ltd) which is a commercial company aimed at developing molecular diagnostics in infection and antimicrobial and AMR stewardship. NMB, GD and ACM are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd (CID Ltd). All other authors declare no conflict of interest., (Copyright: © 2021 Navapurkar V et al.)

Background: Head and neck surgeons often face a challenge in order to achieve adequate three-dimensional resection of tumours in the oral cavity, especially in the dentate patient., Methods: We compared the outcomes of lip-split mandibulotomy and trans-oral access, respectively, in patients treated for primary pT2 oral tongue SCC with regard to the status of the resection margins and the incidence of tumour recurrence., Results: Multivariate analysis showed a non-significant effect of the surgical technique used to the reported recurrence, F(1, 224) = 0.350, p = .555 and a significant effect on the margins achieved F(1, 224) = 11.381, p = .001., Conclusions: Defects after excision of larger and more posterior tumours that are going to be reconstructed with free flaps represent a more probable indication for using an osteotomy access technique. Lip-split mandibulotomy is a low-morbidity technique which can deliver a sound oncological outcome and can be relatively easily taught to less experienced surgeons., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment., (© 2020 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.)

Background: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours., Methods: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials., Results: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001)., Conclusion: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours., Clinical Trial Registration: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

Objective: To evaluate the value of fetal scalp blood sampling (FBS) as an adjunct test to cardiotocography, to predict adverse neonatal outcomes., Study Design: A multicentre service evaluation observational study in forty-four maternity units in the UK. We collected data retrospectively on pregnant women with singleton pregnancy who received FBS in labour using a standardised data collection tool. The primary outcome was prediction of neonatal acidaemia diagnosed as umbilical cord arterial pH < 7.05, the secondary outcomes were the prediction of Apgar scores<7 at 1st and 5th minutes and admission to the neonatal intensive care unit (NICU). We evaluated the correlation between the last FBS blood gas before birth and the umbilical cord blood and adjusted for time intervals. We constructed 2 × 2 tables to calculate the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) and generated receiver operating curves to report on the Area Under the Curve (AUC)., Results: In total, 1422 samples were included in the analysis; pH values showed no correlation (r = 0.001, p = 0.9) in samples obtained within an hour (n = 314), or within half an hour from birth (n = 115) (r=-0.003, p = 0.9). A suboptimal FBS pH value (<7.25) had a poor sensitivity (22%) and PPV (4.9%) to predict neonatal acidaemia with high specificity (87.3%) and NPV (97.4%). Similar performance was noted to predict Apgar scores <7 at 1st (sensitivity 14.5%, specificity 87.5%, PPV 23.4%, NPV 79.6%) and 5th minute (sensitivity 20.3%, specificity 87.4%, PPV 7.6%, NPV 95.6%), and admission to NICU (sensitivity 20.3%, specificity 87.5%, PPV 13.3%, NPV 92.1%). The AUC for FBS pH to predict neonatal acidaemia was 0.59 (95%CI 0.59-0.68, p = 0.3) with similar performance to predict Apgar scores<7 at 1st minute (AUC 0.55, 95%CI 0.51-0.59, p = 0.004), 5th minute (AUC 0.55, 95%CI 0.48-0.62, p = 0.13), and admission to NICU (AUC 0.58, 95%CI 0.52-0.64, p = 0.002). Forty-one neonates had acidaemia (2.8%, 41/1422) at birth. There was no significant correlation in pH values between the FBS and the umbilical cord blood in this subgroup adjusted for sampling time intervals (r = 0.03, p = 0.83)., Conclusions: As an adjunct tool to cardiotocography, FBS offered limited value to predict neonatal acidaemia, low Apgar Scores and admission to NICU., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To characterize reproducibility of patient breath-hold positioning and compare tracking system performance for Deep Inspiration Breath Hold (DIBH) gated left breast radiotherapy., Methods: 29 consecutive left breast DIBH patients (655 fractions) were treated under the guidance of Calypso surface beacons with audio-feedback and 35 consecutive patients (631 fractions) were treated using C-RAD Catalyst HD surface imaging with audiovisual feedback. The Calypso system tracks a centroid determined by two radio-frequency transponders, with a manually enforced institutional tolerance, while the surface image based CatalystHD system utilizes real-time biometric feedback to track a pre-selected point with an institutional tolerance enforced by the Elekta Response gating interface. DIBH motion data from Calypso was extracted to obtain the displacement of breath hold marker in ant/post direction from a set-zero reference point. Ant/post point displacement data from CatalystHD was interpreted by computing the difference between raw tracking points and the center of individual gating windows. Mean overall errors were compared using Welsh's unequal variance t-test. Wilcoxon rank sum test were used for statistical analysis with P < 0.05 considered significant., Results: Mean overall error for Calypso and CatalystHD were 0.33 ± 1.17 mm and 0.22 ± 0.43 mm, respectively, with t-test comparison P-value < 0.034. Absolute errors for Calypso and CatalystHD were 0.95 ± 0.75 mm and 0.38 ± 0.30 mm, respectively, with Wilcoxon rank sum test P-value <2×10 -16 . Average standard deviation per fraction was found to be 0.74 ± 0.44 mm for Calypso patients versus 0.54 ± 0.22 mm for CatalystHD., Conclusion: Reduced error distribution widths in overall positioning, deviation of position, and per fraction deviation suggest that the use of functionalities available in CatalystHD such as audiovisual biofeedback and patient surface matching improves accuracy and stability during DIBH gated left breast radiotherapy., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

IntroductionMajor-incident triage ensures effective emergency care and utilization of resources. Prehospital emergency care providers are often the first medical professionals to arrive at any major incident and should be competent in primary triage. However, various factors (including level of training) influence their triage performance.Hypothesis/ProblemThe aim of this study was to determine the difference in major-incident triage performance between different training levels of prehospital emergency care providers in South Africa utilizing the Triage Sieve algorithm., Methods: This was a cross-sectional study involving differently trained prehospital providers: Advanced Life Support (ALS); Intermediate Life Support (ILS); and Basic Life Support (BLS). Participants wrote a validated 20-question pre-test before completing major-incident training. Two post-tests were also completed: a 20-question written test and a three-question face-to-face evaluation. Outcomes measured were triage accuracy and duration of triage. The effect of level of training, gender, age, previous major-incident training, and duration of service were determined., Results: A total of 129 prehospital providers participated. The mean age was 33.4 years and 65 (50.4%) were male. Most (n=87; 67.4%) were BLS providers. The overall correct triage score pre-training was 53.9% (95% CI, 51.98 to 55.83), over-triage 31.4% (95% CI, 29.66 to 33.2), and under-triage 13.8% (95% CI, 12.55 to 12.22). Post-training, the overall correct triage score increased to 63.6% (95% CI, 61.72 to 65.44), over-triage decreased to 17.9% (95% CI, 16.47 to 19.43), and under-triage increased to 17.8% (95% CI, 16.40 to 19.36). The ALS providers had both the highest likelihood of a correct triage score post-training (odds ratio 1.21; 95% CI, 0.96-1.53) and the shortest duration of triage (median three seconds, interquartile range two to seven seconds; P=.034). Participants with prior major-incident training performed better (P=.001)., Conclusion: Accuracy of major-incident triage across all levels of prehospital providers in South Africa is less than optimal with non-significant differences post-major-incident training. Prior major-incident training played a significant role in triage accuracy indicating that training should be an ongoing process. Although ALS providers were the quickest to complete triage, this difference was not clinically significant. The BLS and ILS providers with major-incident training can thus be utilized for primary major-incident triage allowing ALS providers to focus on more clinical roles. AlenyoAN, SmithWP, McCaulM, Van HovingDJ. A comparison between differently skilled prehospital emergency care providers in major-incident triage in South Africa. Prehosp Disaster Med. 2018;33(6):575-580.

Purpose: The review of a radiation therapy plan by a physicist prior to treatment is a standard tool for ensuring the quality of treatments. However, little is known about how well this task is performed in practice. The goal of this study is to present a novel method to measure the effectiveness of physics plan review by introducing simulated errors into computerized "mock" treatment charts and measuring the performance of plan review by physicists., Methods: We generated six simulated treatment charts containing multiple errors. To select errors, we compiled a list based on events from a departmental incident learning system and an international incident learning system (SAFRON). Seventeen errors with the highest scores for frequency and severity were included in the simulations included six mock treatment charts. Eight physicists reviewed the simulated charts as they would a normal pretreatment plan review, with each chart being reviewed by at least six physicists. There were 113 data points for evaluation. Observer bias was minimized using a simple error vs hidden error approach, using detectability scores for stratification. The confidence interval for the proportion of errors detected was computed using the Wilson score interval., Results: Simulated errors were detected in 67% of reviews [58-75%] (95% confidence interval [CI] in brackets). Of the errors included in the simulated plans, the following error scenarios had the highest detection rates: an incorrect isocenter in DRR (93% [70-99%]), a planned dose different from the prescribed dose (92% [67-99%]) and invalid QA (85% [58-96%]). Errors with low detection rates included incorrect CT dataset (0%, [0-39%]) and incorrect isocenter localization in planning system (38% [18-64%]). Detection rates of errors from simulated charts were compared against observed detection rates of errors from a departmental incident learning system., Conclusions: It has been notoriously difficult to quantify error and safety performance in oncology. This study uses a novel technique of simulated errors to quantify performance and suggests that the pretreatment physics plan review identifies some errors with high fidelity while other errors are more challenging to detect. These data will guide future work on standardization and automation. The example process studied here was physics plan review, but this approach of simulated errors may be applied in other contexts as well and may also be useful for training and education purposes., (© 2018 American Association of Physicists in Medicine.)

Clinical trial design most often focuses on a single or several related outcomes with corresponding calculations of statistical power. We consider a clinical trial to be a decision problem, often with competing outcomes. Using a current controversy in the treatment of HPV-positive head and neck cancer, we apply several different probabilistic methods to help define the range of outcomes given different possible trial designs. Our model incorporates the uncertainties in the disease process and treatment response and the inhomogeneities in the patient population. Instead of expected utility, we have used a Markov model to calculate quality adjusted life expectancy as a maximization objective. Monte Carlo simulations over realistic ranges of parameters are used to explore different trial scenarios given the possible ranges of parameters. This modeling approach can be used to better inform the initial trial design so that it will more likely achieve clinical relevance.

Background: Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients., Methods: An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses., Results: Upfront proton treatment costs exceeded that of photons [$16,730.37 (3DCRT), $23,893.83 (IMRT), $41,061.80 (protons)]. Based upon expected population pneumonitis and esophagitis rates for each modality, protons would be expected to recover $1,065.62 and $1,139.63 of the cost difference compared to 3DCRT or IMRT. For patients treated with IMRT experiencing grade 4 pneumonitis or grade 4 esophagitis, costs exceeded patients treated with protons without this toxicity. 3DCRT patients with grade 4 esophagitis had higher costs than proton patients without this toxicity. For the risk group analysis, high risk patients (age >65, carboplatin/paclitaxel) benefited more from proton therapy. A biomarker may allow patient selection for proton therapy, although the AUC alone is not sufficient to determine if the biomarker is clinically useful., Conclusions: The comparison between proton and photon/X-ray radiation therapy for NSCLC needs to consider both the up-front cost of treatment and the possible long term cost of complications. In our analysis, current costs favor X-ray therapy. However, relatively small reductions in the cost of proton therapy may result in a shift to the preference for proton therapy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: This study investigated the clinical relevance of the distance between the resection margin and tumor cells of the primary sites for oral squamous cell carcinoma, with particular attention to local recurrence rate., Patients and Methods: All patients diagnosed with oral squamous cell carcinoma from 1995 to 2006 and treated primarily with surgery formed the initial cohort of the study. Patient with various degrees of dysplasia in the margin, patients who received radiotherapy, and patients who died of causes other than oral cancer were excluded. Margins 1 to 5 mm were considered close. A margin of at least 5 mm was considered free of disease (clear). Local recurrence was defined as tumor development at the site of the primary tumor during the follow-up period (≥5 yr). The Fisher exact test was used to determine the relevance of the differences between the studied groups (free vs close margins) in relation to local recurrence., Results: Histologic analysis of the specimens was performed. Of the 53 patients, 32 had free margins and 3 of the 32 had a local recurrence. In addition, 21 patients had close margins and 3 of the 21 had a local recurrence. The difference between the 2 groups was not statistically relevant., Conclusions: The authors advocate that the strategy of using close resection margins as a generic indicator for local recurrence and adverse prognosis might have to be reassessed. The histopathologic evidence of tumor cells within a distance less than 0.5 cm from the surgical margins does not necessarily seem to offer a certain indication for additional treatment. Other prognostic factors, such as involvement of cervical lymph nodes and tumor depth, must be considered in the decision making for further treatment., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The endocannabinoid system is involved in many areas of physiological function and homeostasis. Cannabinoid receptors are expressed in the peripheral and central nervous system and on immune cells, all areas ideally suited to modulation of pain processing. There are a wealth of preclinical data in a number of acute, chronic, neuropathic and cancer pain models that have demonstrated a potent analgesic potential for cannabinoids, especially in patients with cancer. However, although there are some positive results in pain of cancer patients, the clinical evidence for cannabinoids as analgesics has not been convincing and their use can only be weakly recommended. The efficacy of cannabinoids seems to have been 'lost in translation' which may in part be related to using extracts of herbal cannabis rather than targeted selective full agonists at the cannabinoid CB1 and CB2 receptors., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this report is to present an overview of the authors' experience in treating parotid gland tumors for a period of 10 years. This report describes patients' demographics, surgical outcomes, and complications and discusses the management of benign disease with particular emphasis on the importance of facial nerve dissection., Patients and Methods: A total of 205 consecutive patients with different parotid gland tumors underwent surgery at Northampton General Hospital (Northampton, UK) from October 2000 to November 2010. Data were prospectively collected and entered into an electronic database. Patients' demographics, clinical tumor size, type of operation, fine-needle aspiration result, facial nerve status, final histopathologic report, and intraoperative and postoperative complications were recorded and analyzed., Results: This study confirmed that good results in low recurrence rate and minimal risk of facial nerve weakness can be achieved with operations less aggressive than traditional superficial parotidectomy, such as partial superficial parotidectomy. Transient facial nerve palsy was significantly more frequent after total (40%; P < .001) and superficial (28%; P < .05) parotidectomy, respectively, than after partial superficial parotidectomy (9.6%)., Conclusion: Because the risk or recurrence is higher when surgery is performed by inexperienced surgeons, the authors advocate that parotid gland surgery should be performed by adequately trained operators and the surgical specimen ideally should be examined by a histopathologist experienced in the diagnosis of salivary gland tumors. Recurrence rate for these tumors increases with time; therefore, long-term follow-up is required for these patients., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Multisession stereotactic radiation therapy is increasingly being seen as a preferred option for intracranial diseases in close proximity to critical structures and for larger target volumes. The objective of this study is to investigate the reproducibility of the Extend system from Elekta. A retrospective review was conducted for all patients treated with multisession Gamma Knife between July 2010 and June 2015, including both malignant and benign lesions. Eighty-four patients were treated in this 5-year span. The average residual daily setup uncertainty was 0.48 (0.19) mm. We compare measurements of setup uncertainty from the Extend system to measurements performed with a linac-based approach previously used in our center. The Extend system has significantly reduced setup uncertainty for fractionated intracranial treatments at our institution. Positive results were observed in a small population of edentulous patients. The Extend system compares favorably with other approaches to delivering intracranial stereotactic radiotherapy and is a robust, simple-to-use, and precise method for treating multisession intracranial lesions.

Purpose: The aim of this study is to present the survival rates in patients treated for oral cancer with primary surgery in a large district general hospital. We discuss the influence of the most significant prognostic factors on survival and compare our results with larger centres specializing in the management of oral cancer., Methods: All patients diagnosed with oral cancer from 1995 to 2006 and were treated in the Department had their details entered prospectively onto a computerized database. Demographic details of patients, type of treatment, pathological stage of tumor (TNM), local and regional recurrence rate, overall survival, disease specific survival and incidence of involved margins were recorded and calculated., Results: Of the 178 patients, 96 (54 %) were alive and free of oral cancer 5 years after surgery. Forty-four patients died of oral cancer (24.7 %) but 38 (21.3 %) died of other causes. The overall survival rate after primary surgery in relation to stage was: I 84 %, II 71 %, III 36 % and IV 28 %., Discussion: As almost half of our patients presented with advanced cancer and had discouraging survival rates, we emphasize the need for early recognition of the disease. Advanced disease signifies difficulty in obtaining clear margins which actually indicates a higher recurrence rate. 25 % of our patients died of oral cancer within 5 years of surgery which highlights the poor prognosis that recurrence carries after treatment. Effective educational campaign with purpose to raise oral cancer awareness and earlier referral may result in improvement of survival.

The clearest phenotypic characteristic of microbial cells is their shape, but we do not understand how cell shape affects the dense communities, known as biofilms, where many microbes live. Here, we use individual-based modeling to systematically vary cell shape and study its impact in simulated communities. We compete cells with different cell morphologies under a range of conditions and ask how shape affects the patterning and evolutionary fitness of cells within a community. Our models predict that cell shape will strongly influence the fate of a cell lineage: we describe a mechanism through which coccal (round) cells rise to the upper surface of a community, leading to a strong spatial structuring that can be critical for fitness. We test our predictions experimentally using strains of Escherichia coli that grow at a similar rate but differ in cell shape due to single amino acid changes in the actin homolog MreB. As predicted by our model, cell types strongly sort by shape, with round cells at the top of the colony and rod cells dominating the basal surface and edges. Our work suggests that cell morphology has a strong impact within microbial communities and may offer new ways to engineer the structure of synthetic communities., Competing Interests: The authors declare no conflict of interest.

Purpose: To build a new treatment planning approach that extends beyond radiation transport and IMRT optimization by modeling the radiation therapy process and prognostic indicators for more outcome-focused decision making., Methods: An in-house treatment planning system was modified to include multiobjective inverse planning, a probabilistic outcome model, and a multi-attribute decision aid. A genetic algorithm generated a set of plans embodying trade-offs between the separate objectives. An influence diagram network modeled the radiation therapy process of prostate cancer using expert opinion, results of clinical trials, and published research. A Markov model calculated a quality adjusted life expectancy (QALE), which was the endpoint for ranking plans., Results: The Multiobjective Evolutionary Algorithm (MOEA) was designed to produce an approximation of the Pareto Front representing optimal tradeoffs for IMRT plans. Prognostic information from the dosimetrics of the plans, and from patient-specific clinical variables were combined by the influence diagram. QALEs were calculated for each plan for each set of patient characteristics. Sensitivity analyses were conducted to explore changes in outcomes for variations in patient characteristics and dosimetric variables. The model calculated life expectancies that were in agreement with an independent clinical study., Conclusions: The radiation therapy model proposed has integrated a number of different physical, biological and clinical models into a more comprehensive model. It illustrates a number of the critical aspects of treatment planning that can be improved and represents a more detailed description of the therapy process. A Markov model was implemented to provide a stronger connection between dosimetric variables and clinical outcomes and could provide a practical, quantitative method for making difficult clinical decisions.

Monthly QA is recommended to verify the constancy of high-energy electron beams generated for clinical use by linear accelerators. The tolerances are defined as 2%/2 mm in beam penetration according to AAPM task group report 142. The practical implementation is typically achieved by measuring the ratio of readings at two different depths, preferably near the depth of maximum dose and at the depth corresponding to half the dose maximum. Based on beam commissioning data, we show that the relationship between the ranges of energy ratios for different electron energies is highly nonlinear. We provide a formalism that translates measurement deviations in the reference ratios into change in beam penetration for electron energies for six Elekta (6-18 MeV) and eight Varian (6-22 MeV) electron beams. Experimental checks were conducted for each Elekta energy to compare calculated values with measurements, and it was shown that they are in agreement. For example, for a 6 MeV beam a deviation in the measured ionization ratio of ± 15% might still be acceptable (i.e., be within ± 2 mm), whereas for an 18 MeV beam the corresponding tolerance might be ± 6%. These values strongly depend on the initial ratio chosen. In summary, the relationship between differences of the ionization ratio and the corresponding beam energy are derived. The findings can be translated into acceptable tolerance values for monthly QA of electron beam energies.

Background: Major incidents put pressure on any health system. There are currently no studies describing the epidemiology of major incidents in South Africa (SA). The lack of data makes planning for major incidents and exercising of major incident plans difficult., Objective: To describe the epidemiology of major incidents in the Western Cape Province, SA., Methods: A retrospective analysis of the Western Cape Major Incident database was conducted for the period 1 December 2008-30 June 2014. Variables collected related to patient demographics and incident details. Summary statistics were used to describe all variables., Results: Seven hundred and seventy-seven major incidents were reviewed (median n=11 per month). Most major incidents occurred in the City of Cape Town (57.8%, n=449), but the Central Karoo district had the highest incidence (11.97/10 000 population). Transport-related incidents occurred most frequently (94.0%, n=730). Minibus taxis were involved in 312 major incidents (40.2%). There was no significant difference between times of day when incidents occurred. A total of 8,732 patients were injured (median n=8 per incident); ten incidents involved 50 or more victims. Most patients were adults (80.0%, n=6 986) and male (51.0%, n=4,455). Of 8,440 patients, 630 (7.5%) were severely injured. More than half of the patients sustained minor injuries (54.6%, n=4,605)., Conclusion: Major incidents occurred more often than would have been expected compared with other countries, with road traffic crashes the biggest contributor. A national database will provide a better perspective of the burden of major incidents.

Introduction: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized., Methods: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers., Results: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification., Conclusion: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.

A population-based cohort study on pediatric infectious diseases was established at Khanh Hoa Province, central Vietnam in 2006, to determine the etiology and risk factors for severe pediatric infectious diseases (SPID) such as acute respiratory infection (ARI), diarrhea and dengue which are the major causes of under 5 mortality. A population census survey was conducted in Nha-Trang and Ninh-Hoa to collect demographic, social-behavioral data and disease burden on SPID. The study site covered a population of 353,525 residing in 75,826 households with 24,781 children less than 5 years. Hospital databases from two hospitals covering the region were obtained. Linking the census and hospital databases, we were able to investigate on a variety of SPID such as environmental tobacco smoking exposure and increased risked of pediatric pneumonia hospitalization, population density, water supply and risk of dengue fever and animal livestock and risk of hospitalized diarrhea. To determine incidence, viral etiology and risk factors for pediatric ARI/pneumonia, we setup a population based prospective hospitalized Pediatric ARI surveillance at Khanh Hoa General Hospital, Nha-Trang in February 2007. The study has revealed RSV, rhinovirus and influenza A as major viral pathogens, role of multiple viral infection and its interaction with bacteria in the development of pneumonia. In addition, we are also conducting a birth cohort study to investigate the incidence of congenital infection and its impact on physical-neurological development, and role of host genetic polymorphism on SPID hospitalization in Vietnam. Population mobility, high cost of regular census update and low mortality are the challenges.

Background: A helicopter emergency medical service (HEMS) was established in 2005 in Richards Bay, KwaZulu-Natal, South Africa, to provide primary response and inter-facility transfers to a largely rural area with a population of 3.4 million people., Objective: To describe the first 5 years of operation of the HEMS., Methods: A chart review of all flights from 1 January 2006 to 31 December 2010 was conducted., Results: A total of 1 429 flights were undertaken; 3 were excluded from analysis (missing folders). Most flights (88.4%) were inter-facility transfers (IFTs). Almost 10% were cancelled after takeoff. The breakdown by age was 61.9% adult, 15.1% paediatric and 21.6% neonate. The main indications for IFTs were obstetrics (34.5%), paediatrics (27.9%) and trauma (15.9%). For primary response most cases were trauma (72.9%) and obstetrics (11.3%). The median on-scene time for neonates was significantly longer (48 min, interquartile range (IQR) 35 - 64 min) than that for adults (36 min, IQR 26 - 48; p < 0.001) and paediatrics (36 min, IQR 25 - 51; p < 0.02). On-scene times for doctor-paramedic crews (45 min, IQR 27 - 50) were significantly longer than for paramedic-only crews (38 min, IQR 27 - 57; p < 0.001)., Conclusion: The low flight-to-population ratio and primary response rate may indicate under-utilisation of the air medical service in an area with a shortage of advanced life support crews and long transport distances. Further studies on HEMSs in rural Africa are needed, particularly with regard to cost-benefit analyses, optimal activation criteria and triage systems.

To simulate long time and length scale processes involving DNA it is necessary to use a coarse-grained description. Here we provide an overview of different approaches to such coarse-graining, focussing on those at the nucleotide level that allow the self-assembly processes associated with DNA nanotechnology to be studied. OxDNA, our recently-developed coarse-grained DNA model, is particularly suited to this task, and has opened up this field to systematic study by simulations. We illustrate some of the range of DNA nanotechnology systems to which the model is being applied, as well as the insights it can provide into fundamental biophysical properties of DNA.

The primary purpose of this two-phased study was to examine the structural validity and statistical utility of a racism scale specific to Black men who have sex with men (MSM) who resided in the Washington, DC, metropolitan area and Baltimore, Maryland. Phase I involved pretesting a 10-item racism measure with 20 Black MSM. Based on pretest findings, the scale was adapted into a 21-item racism scale for use in collecting data on 166 respondents in Phase II. Exploratory factor analysis of the 21-item racism scale resulted in a 19-item, two-factor solution. The two factors or subscales were the following: General Racism and Relationships and Racism. Confirmatory factor analysis was used in testing construct validity of the factored racism scale. Specifically, the two racism factors were combined with three homophobia factors into a confirmatory factor analysis model. Based on a summary of the fit indices, both comparative and incremental were equal to .90, suggesting an adequate convergence of the racism and homophobia dimensions into a single social oppression construct. Statistical utility of the two racism subscales was demonstrated when regression analysis revealed that the gay-identified men versus bisexual-identified men in the sample were more likely to experience increased racism within the context of intimate relationships and less likely to be exposed to repeated experiences of general racism. Overall, the findings in this study highlight the importance of continuing to explore the psychometric properties of a racism scale that accounts for the unique psychosocial concerns experienced by Black MSM.

Background: High prevalence of physical inactivity contributes to adverse health outcomes. Active transportation (cycling or walking) is associated with better health outcomes, and bike-sharing programs can help communities increase use of active transportation., Community Context: The Minneapolis Health Department funded the Nice Ride Minnesota bike share system to expand to the Near North community in Minneapolis, Minnesota. Near North is a diverse, low-income area of the city where residents experience health disparities, including disparities in physical activity levels., Methods: The installation of new bike share kiosks in Near North resulted in an environmental change to support physical activity. Community engagement was conducted pre-intervention only and consisted of focus groups, community meetings, and interviews. Postintervention data on bike share trips and subscribers were collected to assess intervention effectiveness., Outcome: Focus group participants offered insights on facilitators and barriers to bike share and suggested system improvements. Community engagement efforts showed that Near North residents were positive about Nice Ride and wanted to use the system; however, the numbers of trips and subscriptions in Near North were low., Interpretation: Results show that the first season of the expansion was moderately successful in improving outreach efforts and adapting bike share to meet the needs of low-income populations. However, environmental change without adequate, ongoing community engagement may not be sufficient to result in behavior change.

Objective: The aim of this study was to identify the relative risk of damage to the inferior dental (ID) and lingual nerves in patients undergoing lower third molar removal., Study Design: A single surgeon reviewed 1,000 patients., Results: Temporary ID neurosensory deficit was highest (11%) when root apices were intimate to the ID nerve and lowest (0.9%) when close or distant from the nerve. Permanent ID neurosensory deficit was 0.4% per tooth but only when intimate to the canal. Bone removal, tooth division, and lingual split technique increase the risk of excessive hemorrhage which appears to be linked to the highest risk of temporary ID neurosensory deficit (20%). Permanent lingual nerve injury was rare (0.06%) and not related to lingual retraction., Conclusions: Preoperative warning for lower third molar removal can be individually tailored depending on the intimacy of the ID canal to the root apices and the anticipated surgical technique., (Crown Copyright © 2013. Published by Mosby, Inc. All rights reserved.)

Introduction: The aim of this study was to describe the current state of disaster preparedness in hospitals in the public sector in the Western Cape, South Africa with the advent of the FIFA 2010 Soccer World Cup. The objectives included the completion of a self-reported assessment of readiness at all Western Cape public sector hospitals, to identify best practice and shortfalls in these facilities, as well as putting forward recommendations for improving disaster preparedness at these hospitals., Methods: The National Department of Health, as part of the planning for the FIFA 2010 World Cup, appointed an expert committee to coordinate improvements in disaster medicine throughout the country. This workgroup developed a Self Reported Hospital Assessment Questionnaire, which was sent to all hospitals across the country. Data only were collected from public hospitals in the Western Cape and entered onto a purpose-built database. Basic descriptive statistics were calculated. Ethical approval was obtained from the Health Sciences Faculty Research Committee of the University of Cape Town., Results: Twenty-seven of the 41 (68%) public hospitals provided completed data on disaster planning. The study was able to ascertain what infrastructure is available and what planning already has been implemented at these institutions., Recommendations: Most hospitals in the Western Cape have a disaster plan for their facility. Certain areas need more focus and attention; these include: (1) increasing collaborative partnerships; (2) improving HAZMAT response resources; (3) specific plans for vulnerable populations; (4) contingency plans for communication failure; (5) visitor, media and VIP dedicated areas and personnel; (6) evacuation and surge capacity plans; and (7) increased attention to training and disaster plan exercises.