Captain Scott rewrote his story: January–June 1911

This article reveals that Captain Robert Falcon Scott rewrote his Terra Nova journals for the period 24 January to 18 June 1911, making extensive changes, in places. He made carbon copies of his journal from then until 31 October 1911. The Royal Geographical Society (with IBG) holds the combined manuscript as Carbon copy of diary as leader of British Antarctic Expedition, Jan. to Oct. 1911 with reference number RFS/1. This little-known version of Scott’s journals has apparently been overlooked by many researchers and scholars. The main research question addressed by the article is: “What was the significance of Captain Scott rewriting his story?” The article reviews two versions of Scott’s story – the published narrative Scott’s Last Expedition, and RFS/1. It investigates the provenance of each version and then reviews differences between the two texts. Three key differences stand out, suggesting the underlying pressures that drove Scott to rewrite his story in mid-1911. The article touches upon editorial changes made by Leonard Huxley in compiling Scott’s Last Expedition and contrasts those changes with changes made by Scott when rewriting the same passages. It also investigates the provenance of a typescript version of RFS/1 held by Canterbury Museum.

Rationale, design and protocol of a cross-sectional study on pregnancy-related cardiovascular diseases in Tanzania (PRECARDT): burden, characterisation and prognostic significance at delivery

IntroductionThe paucity of data describing cardiovascular disease (CVD) in pregnancy in many parts of Africa including Tanzania has given rise to challenges in proper management by the healthcare providers. This study is set out to (1) determine the prevalence of a range of CVDs during pregnancy in women attending antenatal clinics in Tanzania and (2) determine the impact of these CVDs on maternal and fetal outcomes at delivery.Methods and analysisThis is a cross-sectional study with a prospective component to be conducted in two referral hospitals in Tanzania. Pregnant women aged ≥18 years diagnosed with a CVD during the antenatal period are being identified and extensively characterised by performing clinical assessment, modified WHO staging, electrocardiography, echocardiography and laboratory tests. Patients identified with CVDs (exposed) and a subset without (unexposed) will be followed up to determine maternal and fetal outcomes at delivery. A minimum sample of 1560 will be sufficient to estimate the prevalence of CVDs with a 95% CI of 2.75% to 5.25%.Ethics and disseminationThe study is being conducted in accordance with the Helsinki declaration on studies involving human subjects. Ethical approvals have been obtained from Muhimbili University (reference number DA.282/298/01.C/) and Bugando Medical Centre (reference number CREC/330/2019) Ethics Committees. Informed consent is sought from all potential participants before any interview or investigations are performed. Study findings will be disseminated to the scientific community through different methods. Results will also be communicated to policymakers and to the public, as appropriate.

Survey On Biometric Based ATMs

Nowadays Automated Teller Machines (ATMs) are widely used by people. People are dependent upon ATMs to conveniently meet their day-to-day needs. As it is an important factor there comes security. ATMs are electronic machines that are operated by customers to deposit or withdraw cash from banks. It is observed that the number of crimes related to ATMs is increased hence there is a need to provide better security to ATM machines. There are different technologies that are used to provide security to ATM machine which includes – RFID technology, fingerprint, face recognition, iris scan, OTP, reference number, random keypad, etc. In a traditional ATM system card and PIN numbers are used for authentication, where security plays a big concern, such as losing cards, stolen pin numbers, card cloning, shoulder surfing, fake keyboard, skimming, etc. In order to overcome these issues, this paper discusses various systems where ATM cards and pins are replaced by biometrics and how they made ATMs more secure.

Development and external validation of a nomogram for neurosyphilis diagnosis among non-HIV patients: a cross-sectional study

Background The diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests. Therefore, a convenient diagnostic nomogram for neurosyphilis is warranted. This study aimed to construct diagnostic models for diagnosing neurosyphilis. Methods This cross-sectional study included data of two patient cohorts from Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin Hospital between September 2019 and April 2021 as the development cohort and the external validation cohort, respectively. A diagnostic model using logistic regression analysis was constructed to readily provide the probability of diagnosis at point of care and presented as a nomogram. The clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) and Harrell concordance (Harrell C) index for discrimination and calibration plots for accuracy, which adopted bootstrap resampling 500 times. Results One hundred forty-eight and 67 patients were included in the development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive neurosyphilis under the criteria of positive results in both CSF treponemal and non-treponemal tests. In the development cohort, male, psychiatric behaviour disorders, and serum toluidine red unheated serum test were selected as diagnostic indicators applying a stepwise procedure in multivariable logistic model. The model reached 80% specificity, 79% sensitivity, and 0·85 area under the curves (AUC) (95% confidence interval, 0·76–0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive neurosyphilis was 0·71. Conclusions A convenient model using gender, presence of psychiatric behaviour disorders, and serum TRUST titre was developed and validated to indicate diagnostic results in patients suspected of neurosyphilis. Checking the model value of factors on nomogram is a feasible way to assist clinicians and primary health servers in updating patients’ medical charts and making a quantitatively informed decision on neurosyphilis diagnosis. Trial registration This research was retrospectively registered in the Ethics committee on biomedical research, West China Hospital of Sichuan University. The research registration and committee’s reference number was 1163 in 2020 approval.

Prospective pilot study protocol evaluating the safety and feasibility of robot-assisted nipple-sparing mastectomy (RNSM)

IntroductionNipple-sparing mastectomy (NSM) can be performed for the treatment of breast cancer and risk reduction, but total mammary glandular excision in NSM can be technically challenging. Minimally invasive robot-assisted NSM (RNSM) has the potential to improve the ergonomic challenges of open NSM. Recent studies in RNSM demonstrate the feasibility and safety of the procedure, but this technique is still novel in the USA.Methods and analysisThis is a single-arm prospective pilot study to determine the safety, efficacy and potential risks of RNSM. Up to 12 RNSM will be performed to assess the safety and feasibility of the procedure. Routine follow-up visits and study assessments will occur at 14 days, 30 days, 6 weeks, 6 months and 12 months. The primary outcome is to assess the feasibility of removing the breast gland en bloc using the RNSM technique. To assess safety, postoperative complication information will be collected. Secondary outcomes include defining benefits and challenges of RNSM for both surgeons and patients using surveys, as well as defining the breast and nipple-areolar complex sensation recovery following RNSM. Mainly, descriptive analysis will be used to report the findings.Ethics and disseminationThe RNSM protocol was reviewed and approved by the US Food and Drug Administration using the Investigational Device Exemption mechanism (reference number G200096). In addition, the protocol was registered with ClinicalTrials.gov (NCT04537312) and approved by The Ohio State University Institutional Review Board, reference number 2020C0094 (18 August 2020). The results of this study will be distributed through peer-reviewed journals and presented at surgical conferences.Trial registration numberNCT04537312.

340 A phase Ib study of the safety and tolerability of pixatimod plus nivolumab in subjects with advanced solid tumors with an expansion cohort in metastatic pancreatic adenocarcinoma (mPDAC)

BackgroundPixatimod is a novel immunomodulatory agent which stimulates dendritic cells (DC) via Toll-Like Receptor (TLR9) pathway to activate natural killer (NK) cells.1 In combination with PD1 inhibitors, it also enhances T cell infiltration in vivo.2 We report on safety, pharmacokinetics (PK) and pharmacodynamics (PD), and antitumor activity of pixatimod plus nivolumab in advanced cancer patients (stage 1) and in an expansion cohort of mPDAC (stage 2).MethodsIn the dose escalation stage (3+3 design), eligible patients (ECOG≤1) with advanced solid malignancies who failed standard therapies received pixatimod once weekly as a 1-hour i.v. infusion plus nivolumab (240 mg, every other week) until disease progression or discontinuation due to intolerability. The primary objective was determination of the maximum tolerated dose (MTD). Secondary objectives evaluated safety, antitumor activity per RECIST v1.1, PK of pixatimod, and PD (PBMC, plasma cytokines and chemokines). Stage 2 comprised mPDAC subjects who had received no more than one prior line of chemotherapy in the metastatic setting.ResultsThe dose-escalation stage recruited 16 subjects across two cohorts (25 & 50 mg pixatimod). Two dose limiting toxicities (DLTs) in 50 mg cohort were pulmonary edema and multi-organ failure. Of note, the subject with multi-organ failure had substantially higher CA19.9, Pan-immune-Inflammatory Value (PIV = Neutrophils x Platelets x Monocytes/Lymphocytes) and interleukins (IL) IL-1α and IL-23 at baseline compared with the cohort. One DLT occurred in the 25 mg cohort, pneumonitis, which was identified as the MTD. A further 14 mPDAC subjects were recruited to the expansion stage (25 mg). Seven SAEs were reported to be possibly or likely related to the combination. No objective responses were reported in the mPDAC stage, the best response was SD (n = 3). In another submitted abstract by Lemech et al, we report two subjects in the dose escalation stage with MSS mCRC were confirmed PR, and data from the amended study to include an MSS mCRC expansion cohort will also be presented. Time versus concentration data for pixatimod in advanced cancer patients was similar to that previously reported in monotherapy setting. In mPDAC subjects, there was minimal immune activation as evidenced by a lack of change in effector memory T cells or NK cells in PBMC, plasma cytokines and chemokines.ConclusionsPixatimod is well tolerated at 25 mg in combination with nivolumab but did not provide clear clinical benefit or evidence of immune activation in the mPDAC cohort.AcknowledgementsResearch funding was provided by Zucero Therapeutics Ltd and Bristol Myers Squibb (BMS), Australia.Trial RegistrationClinical trial informationACTRN12617001573347.ReferencesBrennan TV, Lin L, Brandstadter JD, Rendell VR, Dredge K, Huang X, et al. Heparan sulfate mimetic PG545-mediated antilymphoma effects require TLR9-dependent NK cell activation. J Clin Invest 2016;126(1):207–19.Hammond E, Haynes NM, Cullinane C, Brennan TV, Bampton D, Handley P, et al. Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors. J Immunother Cancer 2018;6(1):54.Ethics ApprovalThe clinical trial entitled “An open-label, multi-centre Phase Ib study of the safety and tolerability of IV infused PG545 in combination with nivolumab in patients with advanced solid tumours with an expansion cohort in patients with metastatic pancreatic cancer. Protocol ZU545102” obtained ethics approval from the Royal Adelaide Hospital (HREC Reference number, HREC/17/RAH/195 and the CALHN Reference number, R20170515) and Bellberry Limited (Application No: 2018-08-695). All participants in the study gave informed consent before taking part in ZU545102.

Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey

Background The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions. Methods The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden. Results In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: − 4.5 (95% CI − 7.8 to − 1.3), p = 0.006, Study 2: − 3.1 (95% CI − 4.6 to − 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: − 6.8 (95% CI − 12.2 to − 1.4), p = 0.013; Study 2: − 4.5 (95% CI − 7.3 to − 1.7), p = 0.002. Conclusions We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules. Trial registration: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759).

The role of scar massage in cleft lip surgery

Introduction: Despite advances in surgical technique for cleft lip, minimal evidence exists for methods of scar management, particularly scar massage. Some parents express concern that lip massage creates pain and distress to their children. This study aims to determine whether scar massage has enough cosmetic advantage to justify its use. Method: We reviewed 33 unilateral complete cleft lip repairs performed at our institution. Information on repair technique, suture material and scar management were recorded. Parent questionnaires and clinical photography were used with a panel of eight trained blinded observers asked to assess photos taken 24 months postoperatively. Scars were graded using a scale of 1 (very poor) to 5 (excellent). Twenty patients were included. Ethics approval was obtained from The Royal Children’s Hospital Melbourne Research Ethics and Governance office with HREC reference number QA/60562/RCHM-2019. Results: Frequency of scar massage was not associated with a better scar score (p= 0.36). Both the technique of repair and type of suture material used had greater effect on scar grading than massage therapy. Discussion: Problematic scarring following cleft lip surgery is a challenging outcome. This is the first study aiming to explore the effect of scar massage following cleft lip surgery. Conclusion: We found no conclusive evidence to support the use of scar massage in the postoperative care of cleft lip patients. Limitations include the retrospective nature of the study, low patient numbers and heterogeneity of surgical techniques. Nevertheless, there was no correlation seen between the frequency of massage and scar quality. Lip scar massage can cause significant pain to patients and distress to their family, warranting further studies to justify its use.

Cognitive-bias modification intervention to improve physical activity in patients following a rehabilitation programme: protocol for the randomised controlled IMPACT trial

IntroductionBeing physically active is associated with a wide range of health benefits in patients. However, many patients do not engage in the recommended levels of physical activity (PA). To date, interventions promoting PA in patients mainly rely on providing knowledge about the benefits associated with PA to develop their motivation to be active. Yet, these interventions focusing on changing patients’ conscious goals have proven to be rather ineffective in changing behaviours. Recent research on automatic factors (eg, automatic approach tendencies) may provide additional targets for interventions. However, the implementation and evaluation of intervention designed to change these automatic bases of PA are rare. Consequently, little is known about whether and how interventions that target automatically activated processes towards PA can be effective in changing PA behaviours. The Improving Physical Activity (IMPACT) trial proposes to fill this knowledge gap by investigating the effect of a cognitive-bias modification intervention aiming to modify the automatic approach towards exercise-related stimuli on PA among patients.Methods and analysisThe IMPACT trial is a single-centre, placebo (sham controlled), triple-blinded, phase 3 randomised controlled trial that will recruit 308 patients enrolled in a rehabilitation programme in the Division of General Medical Rehabilitation at the University Hospital of Geneva (Switzerland) and intends to follow up them for up to 1 year after intervention. Immediately after starting a rehabilitation programme, patients will be randomised (1:1 ratio) to receive either the cognitive-bias modification intervention consisting of a 12-session training programme performed over 3 weeks or a control condition (placebo). The cognitive-bias modification intervention aims to improve PA levels through a change in automatic approach tendencies towards PA and sedentary behaviours. The primary outcome is the sum of accelerometer-based time spent in light-intensity, moderate-intensity and vigorous-intensity PA over 1 week after the cognitive-bias modification intervention (in minutes per week). Secondary outcomes are related to changes in (1) automatic approach tendencies and self-reported motivation to be active, (2) physical health and (3) mental health. Sedentary behaviours and self-reported PA will also be examined. The main time point of the analysis will be the week after the end of the intervention. These outcomes will also be assessed during the rehabilitation programme, as well as 1, 3, 6 and 12 months after the intervention for secondary analyses.Ethics and disseminationThe study will be conducted in accordance with the Declaration of Helsinki. This trial was approved by the Ethics Committee of Geneva Canton, Switzerland (reference number: CCER2019-02257). All participants will give an informed consent to participate in the study. Results will be published in relevant scientific journals and be disseminated in international conferences.Trial registration detailsThe clinical trial was registered at the German clinical trials register (reference number: DRKS00023617); Pre-results.

Higher Termination of Brachial Artery in Cadavers in the Department of Anatomy of a Medical College: A Descriptive Cross-sectional Study

Introduction: The main blood supply for arm is provided by the brachial artery. It shows variation in branching and termination patterns in some individuals. Variation in brachial artery may cause difficulties during various clinical and surgical procedures. The present study aims to find out the prevalence of higher termination of brachial artery in cadavers in the department of anatomy of a medical college. Methods: A descriptive cross-sectional study was carried out from 10th January 2020 to 20th April 2021 after the ethical approval was taken from the Institutional Review Committee of Nobel Medical College (reference number: IRC-NMCTH 280/2020). The study was done in 58 upper limbs of 29 properly embalmed cadavers. Convenient sampling was done. They were carefully dissected. The level of termination of brachial artery was noted. The length of the brachial artery and the distance between its termination and the intercondylar line of humerus was recorded. Results: Higher termination of brachial artery was observed in 3 (5.17%) extremities; one (1.72%) at middle third of arm and two (3.45%) at lower third of arm. In 52 (89.66%) extremities, the site of termination was at the level of neck of radius. The brachial artery terminated a few centimeters below its usual site at the level of upper part of shaft of the radius in 3 (5.17%) extremities. Conclusions: The prevalence of higher termination of brachial artery in cadavers is slightly lower than the studies performed in similar settings. It is not an uncommon finding. It may have impact on clinical and surgical procedures.