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Cell walls of bacteria of the genera Mycobacterium and Corynebacterium contain high levels of (coryno)mycolic acids. These very long chain fatty acids are synthesized on the cytoplasmic leaflet of the inner membrane (IM) prior to conjugation to the disaccharide, trehalose, and transport to the periplasm. Recent studies on Corynebacterium glutamicum have shown that acetylation of trehalose monohydroxycorynomycolate (hTMCM) promotes its transport across the inner membrane. Acetylation is mediated by the membrane acetyltransferase, TmaT, and is dependent on the presence of a putative methyltransferase, MtrP. Here, we identify a third protein that is required for the acetylation and membrane transport of hTMCM. Deletion of the C. glutamicum gene NCgl2761 (Rv0226c in Mycobacterium tuberculosis) abolished synthesis of acetylated hTMCM (AcTMCM), resulting in an accumulation of hTMCM in the inner membrane and reduced synthesis of trehalose dihydroxycorynomycolate (h2TDCM), a major outer membrane glycolipid. Complementation with the NCgl2761 gene, designated here as mmpA, restored the hTMCM:h2TDCM ratio. Comprehensive lipidomic analysis of the ΔtmaT, ΔmtrP and ΔmmpA mutants revealed strikingly similar global changes in overall membrane lipid composition. Our findings suggest that the acetylation and membrane transport of hTMCM is regulated by multiple proteins: MmpA, MtrP and TmaT, and that defects in this process lead to global, potentially compensatory changes in the composition of inner and outer membranes.

Background: Attrition of child sexual abuse (CSA) cases occurs at different stages of investigation, and only a small proportion of the cases reported to police are referred for prosecution. Different factors have been linked with the prosecution of CSA cases; however, little is known about how prosecutors determine which cases should proceed and which should not., Objectives: This paper investigated criteria and thresholds used by prosecuting lawyers in deciding whether a child sexual abuse case should proceed., Participants and Setting: Fifty-six Australian prosecution case files (79 complainants; 58 defendants) were reviewed. The cases included contemporaneous and historical allegations of child sexual abuse, ranging from a single incident to repeated, protracted abuse over a decade., Method: Written notes and emails in prosecutors' files were searched for perceptions of the complainants, decisions to proceed and verdicts., Results: When a complainant was considered inconsistent in some way, giving rise to recorded concerns about their credibility or reliability, 82.3 % of these cases culminated in discontinuance or an acquittal. Conversely, 78 % of cases with complainants who were regarded as largely consistent throughout the investigation resulted in a conviction. Recorded issues with a complainant's memory of the events, cognitive capacity, and confusion about the alleged assault were not associated with case outcomes., Conclusion: Most CSA cases that were referred for prosecution resulted in proceeding with charges against the defendant. Perceived issues with the consistency and credibility of the complainants' evidence were the most important decisional factors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: An important element of reducing the sexual abuse and exploitation of children is to understand the behaviors of individuals who consume child sexual abuse material (CSAM), including the predictors of continued use., Objective: To investigate predictors of 'ever viewing' CSAM and subsequent intentional use among individuals in the community., Method: This study used multivariate logistic regression analysis to identify significant predictors of ever viewing CSAM (n = 742) in an anonymous survey of 5512 Internet users in the community, and of subsequent intentional CSAM use among a subset of 459 CSAM viewers., Results: The characteristics of respondents that were significantly associated with ever viewing CSAM were being male, older in age (25-34 and 55+ years cf. 18-24 years), residing in Australia, New Zealand, or Canada (cf. the United Kingdom), earlier exposure to adult pornography (<14 years), experiencing childhood physical abuse or neglect, viewing bestiality pornography featuring adults, viewing bondage/S&M (BDSM) pornography featuring adults, being likely (self-reported) to have sexual contact with a child, and visiting pedophilic chat forums online. In the subset sample, almost half (218, 47.5 %) viewed CSAM again intentionally after first exposure. Predictors of subsequent intentional viewing of CSAM after adjusting for age and country of residence were being male, ever experiencing loneliness, searching for CSAM intentionally at first exposure, being likely (self-reported) to have sexual contact with a child, and visiting pedophilic chat forums online., Conclusions: The findings have strong implications for prevention of first exposure to CSAM, and of continued CSAM use after exposure does occur., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Pathways of Care Longitudinal Study (POCLS) is the first large-scale prospective longitudinal study of children and young people in out-of-home care in Australia. It includes a cohort of all 4126 children and young people (age 0 to 17 years) who entered out-of-home care for the first time over an 18-month period from May 2010 to October 2011 in New South Wales, with a focus on 2828 of these children with final court orders. It involved interviews with participating caregivers for children on final orders and standardised assessments for the children in their care as well as interviews for 7-17 year-olds, together with linked administrative data from a range of agencies for all 4126 children. Data for the interview cohort includes information on children's development, permanency and wellbeing while in care, tracking their physical health, socio-emotional wellbeing and cognitive development, as well as their experiences in care, and after they exit care to return home, or to guardianship and adoption. POCLS currently includes data from five waves of interviews with caregivers and the children in their care. This special issue includes articles that present findings from a range of analyses across various domains from the first four waves of the study. This introductory article outlines the Australian context of the study, its conceptual framework, design and methodology. Using a range of analytical approaches, the nine articles expose an array of issues, including children's developmental, socio-emotional and academic outcomes and trajectories (including reunification), associated with factors such as placement type, stability, pre-care maltreatment, disability, and age at entry to care, and caregiver stress., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Objective: Single prolonged breath-holds of >5 min can be obtained in cancer patients. Currently, however, the preparation time in each radiotherapy session is a practical limitation for clinical adoption of this new technique. Here, we show by how much our original preparation time can be shortened without unduly compromising breath-hold duration., Methods: 44 healthy subjects performed single prolonged breath-holds from 60% O 2 and mechanically induced hypocapnia. We tested the effect on breath-hold duration of shortening preparation time (the durations of acclimatization, hyperventilation and hypocapnia) by changing these durations and or ventilator settings., Results: Mean original breath-hold duration was 6.5 ± 0.2 (standard error) min. The total original preparation time (from connecting the facemask to the start of the breath-hold) was 26 ± 1 min. After shortening the hypocapnia duration from 16 to 5 min, mean breath-hold duration was still 6.1 ± 0.2 min ( ns vs the original). After abolishing the acclimatization and shortening the hypocapnia to 1 min (a total preparation time now of 9 ± 1 min), a mean breath-hold duration of >5 min was still possible (now significantly shortened to 5.2 ± 0.6 min, p < 0.001). After shorter and more vigorous hyperventilation (lasting 2.7 ± 0.3 min) and shorter hypocapnia (lasting 43 ± 4 s), a mean breath-hold duration of >5 min (5.3 ± 0.2 min, p < 0.05) was still possible. Here, the final total preparation time was 3.5 ± 0.3 min., Conclusions: These improvements may facilitate adoption of the single prolonged breath-hold for a range of thoracic and abdominal radiotherapies especially involving hypofractionation., Advances in Knowledge: Multiple short breath-holds improve radiotherapy for thoracic and abdominal cancers. Further improvement may occur by adopting the single prolonged breath-hold of >5 min. One limitation to clinical adoption is its long preparation time. We show here how to reduce the mean preparation time from 26 to 3.5 min without compromising breath-hold duration.

Objective: Breast cancer radiotherapy is increasingly delivered supine with multiple, short breath-holds. There may be heart and lung sparing advantages for locoregional breast cancer of both prone treatment and in a single breath-hold. We test here whether single prolonged breath-holds are possible in the prone, front crawl position., Methods: 19 healthy volunteers were trained to deliver supine, single prolonged breath-holds with pre-oxygenation and hypocapnia. We tested whether all could achieve the same durations in the prone, front crawl position., Results: 19 healthy volunteers achieved supine, single prolonged breath-holds for mean of 6.2 ± 0.3 min. All were able to hold safely for the same duration while prone (6.1 ± 0.2 min ns . by paired ANOVA). With prone, the increased weight on the chest did not impede chest inflation, nor the ability to hold air in the chest. Thus, the rate of chest deflation (mean anteroposterior deflation movement of three craniocaudally arranged surface markers on the spinal cord) was the same (1.2 ± 0.2, 2.0 ± 0.4 and 1.2 ± 0.4 mm/min) as found previously during supine prolonged breath-holds. No leakage of carbon dioxide or air was detectable into the facemask., Conclusion: Single prolonged (>5 min) breath-holds are equally possible in the prone, front crawl position., Advances in Knowledge: Prolonged breath-holds in the front crawl position are possible and have the same durations as in the supine position. Such training would therefore be feasible for some patients with breast cancer requiring loco-regional irradiation. It would have obvious advantages for hypofractionation.

The CRC has a challenging and ambitious agenda in relation to the protection of children from all forms of violence, particularly the large and increasing numbers of children affected by natural disasters, armed conflict, trafficking, poverty and increasing inequality, displacement and trafficking. In this article, we outline some of the issues in the implementation and understanding of the Convention and highlight three major international developments over the last decade: the adoption of General Comment No 13, the work of the Special Representative of the Secretary General on Violence Against Children, and the adoption of the 2030 Agenda for Sustainable Development by the UN General Assembly in 2005. We also identify four broad domains in which the Convention can and is being used to enhance efforts to ensure the protection of children based on a rights framework - advocacy and litigation, policy design, service delivery and research and monitoring methodology - rather than a welfare-based approach. The key to a rights-based approach in efforts to protect children is a focus on children's right to be involved in decision-making - and in research - that affect their lives., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study of attrition compares the prosecution of child sexual offenses reported while the complainant was still a child with those in which the report was delayed into adulthood; it also compares matters involving adult and young (under 18 years) suspects/defendants. It is based on an analysis of police and court administrative data in New South Wales, Australia over a 14-year period (2003-2016). Only one in five (21.6%) proceeded beyond the investigation stage. Criminal proceedings were more likely to commence when the alleged victim was 7-12 years old at the time of the incident, when the suspect was an adult and at least 10 years older than the victim, and also when the report to police was made when the victim was an adult. Just over half (55.5%) of the matters finalized in court resulted in a conviction. Cases in the higher courts were less likely to be dismissed and more likely to feature guilty pleas and convictions at trial than cases in the lower courts. The overall estimate is that only 12% of offenses reported to police resulted in a conviction, at a relatively stable rate over 14 years. These findings are consistent with those of comparable studies.

Background & Purpose: Multiple, short breath-holds are now used in single radiotherapy treatment sessions. Here we investigated the feasibility and safety of multiple prolonged breath-holds in a single session. We measured how long is a second breath-hold if we prematurely terminate a single, prolonged breath-hold of >5 min either by using a single breath of oxygen (O 2 ), or by reintroducing preoxygenation and hypocapnia. We also investigated the feasibility and safety of undertaking 9 prolonged breath-holds in a row., Materials & Methods: 30 healthy volunteers with no previous breath-holding experience were trained to perform single prolonged breath-holds safely., Results: Their mean single, prolonged breath-hold duration was 6.1 ± 0.3 se minutes (n = 30). In 18/18 subjects, premature termination (at 5.1 ± 0.2 min) with a single breath of 60% O 2 , enabled a 2nd safe breath-hold lasting 3.3 ± 0.2 min. In 18/18 subjects, premature termination at 5.3 ± 0.2 min) by reintroducing preoxygenation and hypocapnia, enabled a 2nd safe breath-hold lasting 5.8 ± 0.3 min. 17/17 subjects could safely perform 9 successive prolonged breath-holds, each terminated (at 4.3 ± 0.2 min) by reintroducing preoxygenation and hypocapnia for 3.1 ± 0.2 min. The 9th unconstrained breath-hold (mean of 6.0 ± 0.3 min) lasted as long as their single breath-hold., Conclusions: Multiple prolonged breath-holds are possible and safe. In a ∼19 min treatment session, it would therefore be possible to have ∼13 min for radiotherapy treatment (3 breath-holds) and ∼6 min for setup and recovery. In a 65 min session, it would be possible to have 41 min for radiotherapy and 25 min for setup and recovery., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Reducing respiratory motion during the delivery of radiation therapy reduces the volume of healthy tissues irradiated and may decrease radiation-induced toxicity. The purpose of this study was to assess the potential for rapid shallow non-invasive mechanical ventilation to reduce internal anatomy motion for radiation therapy purposes., Methods and Materials: Ten healthy volunteers (mean age, 38 years; range, 22-54 years; 6 female and 4 male) were scanned using magnetic resonance imaging during normal breathing and at 2 ventilator-induced frequencies: 20 and 25 breaths per minute for 3 minutes. Sagittal and coronal cinematic data sets, centered over the right diaphragm, were used to measure internal motions across the lung-diaphragm interface. Repeated scans assessed reproducibility. Physiologic parameters and participant experiences were recorded to quantify tolerability and comfort., Results: Physiologic observations and experience questionnaires demonstrated that rapid shallow non-invasive ventilation technique was tolerable and comfortable. Motion analysis of the lung-diaphragm interface demonstrated respiratory amplitudes and variations reduced in all subjects using rapid shallow non-invasive ventilation compared with spontaneous breathing: mean amplitude reductions of 56% and 62% for 20 and 25 breaths per minute, respectively. The largest mean amplitude reductions were found in the posterior of the right lung; 40.0 mm during normal breathing to 15.5 mm (P < .005) and 15.2 mm (P < .005) when ventilated with 20 and 25 breaths per minute, respectively. Motion variations also reduced with ventilation; standard deviations in the posterior lung reduced from 14.8 mm during normal respiration to 4.6 mm and 3.5 mm at 20 and 25 breaths per minute, respectively., Conclusions: To our knowledge, this study is the first to measure internal anatomic motion using rapid shallow mechanical ventilation to regularize and minimize respiratory motion over a period long enough to image and to deliver radiation therapy. Rapid frequency and shallow, non-invasive ventilation both generate large reductions in internal thoracic and abdominal motions, the clinical application of which could be profound-enabling dose escalation (increasing treatment efficacy) or high-dose ablative radiation therapy., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Aims: Oropharyngeal squamous cell carcinoma (OPSCC) can be divided into favourable and poor prognostic groups by association with human papilloma virus (HPV) and smoking. This study prospectively investigated a dose-intensified schedule in poor/intermediate prognosis OPSCC., Materials and Methods: Patients with p16/HPV-negative or p16-positive N2b OPSCC with a greater than 10 pack-year smoking history were eligible. Patients were planned to receive 64 Gy in 25 fractions with cisplatin. The primary end point was absence of grade 3 mucositis at 3 months., Results: Fifteen patients were recruited over 14 months. All patients completed a minimum of 2 years of follow-up. All patients completed full-dose radiotherapy within a median treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at 3 months. There was one grade 4 toxicity event due to cisplatin (hypokalaemia). Complete response rates at 3 months were 100% and 93% for local disease and lymph nodes, respectively. One patient developed metastatic disease and subsequently died. Overall survival at 2 years was 93% (95% confidence interval 61-99%)., Conclusions: The schedule of 64 Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor and intermediate prognosis OPSCC., (Copyright © 2018. Published by Elsevier Ltd.)

Delays in disclosing and reporting child sexual abuse to the police are common, particularly among males and those who have been abused by clergy and others in a position of trust. This study, commissioned by the Royal Commission into Institutional Responses to Child Sexual Abuse, examined the patterns of timely and delayed reporting of sexual offences against children, and the likelihood of legal action commencing. De-identified unit record data for all sexual offences against children reported to the police over 20 years were obtained from official crime statistics agencies in two Australian states. While there were similarities between the two states in terms of the influence of public inquiries on reporting numbers over this period, and in the factors associated with delayed reporting, there were substantial differences in the likelihood of legal action being taken in cases reported by a child or adult complainants. In one state, legal action was more likely with increasing delay, until the delays extended to 10-20 years, after which the likelihood of legal action decreased. In the other state, the pattern was quite different - reports of sexual assault were somewhat more likely to result in legal action with immediate reporting. The least likely to proceed were cases involving young children in more recent years; long delays into adulthood were not necessarily adverse for prosecution., (Copyright © 2017. Published by Elsevier Ltd.)

Flattening filter free (FFF) beams are now commonly available with new standard linear accelerators. These beams have recognised clinical advantages in certain circumstances, most notably the reduced beam-on times for high dose per fraction stereotactic treatments. Therefore FFF techniques are quickly being introduced into clinical use. The purpose of this report is to provide practical implementation advice and references for centres implementing FFF beams clinically. In particular UK-specific guidance is given for reference dosimetry and radiation protection.

As the use of linear accelerators operating in flattening filter-free (FFF) modes becomes more widespread, it is important to have an understanding of the surface doses delivered to patients with these beams. Flattening filter removal alters the beam quality and relative contributions of low-energy X-rays and contamination electrons in the beam. Having dosimetric data to describe the surface dose and buildup regions under a range of conditions for FFF beams is important if clinical decisions are to be made. An Elekta Synergy linac with standard MLCi head has been commissioned to run at 6 MV and 10 MV running with the flattening filter in or out. In this linac the 6 MV FFF beam has been energy-matched to the clinical beam on the central axis (D10). The 10 MV beam energy has not been adjusted. The flattening filter in both cases is replaced by a thin (2 mm) stainless steel plate. A thin window parallel plate chamber has been used to measure a comprehensive set of surface dose data in these beams for variations in field size and SSD, and for the presence of attenuators (wedge, shadow tray, and treatment couch). Surface doses are generally higher in FFF beams for small field sizes and lower for large field sizes with a crossover at 10 × 10 cm2 at 6 MV and 25 × 25 cm2 at 10 MV. This trend is also seen in the presence of the wedge, shadow tray, and treatment couch. Only small differences (< 0.5%) are seen between the beams on varying SSD. At both 6 and 10 MV the filter-free beams show far less variation with field size than conventional beams. By removing the flattening filter, a source of contamination electrons is exchanged for a source of low-energy photons (as these are no longer attenuated). In practice these two components almost balance out. No significant effects on surface dose are expected by the introduction of FFF delivery., (© 2016 The Authors.)

Aims: Between 2012 and 2014 the number of patients treated in the UK with intensity-modulated radiotherapy (IMRT) techniques increased significantly. One reason for this was the radiotherapy innovation fund for the centres in England. Before the announcement of the fund, a survey of radiotherapy centres was carried out in 2012 which collected data on IMRT uptake, obstacles to implementation, equipment used, delivery techniques and verification methods. A repeat survey was carried out in 2014 to identify key changes to IMRT quality assurance and verification practices., Materials and Methods: An online questionnaire was sent out to all 65 UK radiotherapy centres in the summer of 2012 and again in the summer of 2014. Questions covered background and equipment, machine tolerance and quality assurance, machine-based verification, software-based verification and future plans., Results: There have been significant changes in the delivery techniques used for IMRT, with more than twice as many centres reporting the use of volumetric-modulated arc therapy techniques in 2014 compared with 2012. This has been combined with an increase in Monte Carlo-based algorithms in treatment planning systems. In 2012 all centres reported the need to carry out machine-based measurements for IMRT plan verification, dropping to 93% in 2014. Nineteen per cent of centres now report making only one measurement per month for prostate plans and 8% of breast plans never have physical measurements. Most centres use detector arrays for quality assurance measurement (86% in 2012 and 91% in 2014), but a significant number still use film and/or ionisation chambers (51% and 41%). In the analysis of these measurements there has been an increase in the use of tighter criteria. There has been a significant increase in the use of software for verification from 63% in 2012 to 95% in 2014. All centres reported that they needed further resources in order to efficiently achieve the quality assurance required for the number of patients planned to be treated in their centre., Conclusions: The increased numbers of patients being treated with IMRT has meant that there have been significant changes in the way that quality assurance is carried out. These have been mainly in the reduction of measurements and the increase in software-based verification. However, quality assurance is still a significant burden and still has an effect on the numbers of patients who can be treated with IMRT., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)