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Re-planning mid-treatment, with the adjustment of target volumes, has been performed as part of the normal workflow at our institution. We sought to quantify the benefit of this approach and identify factors to optimise plan adaptive strategies.
Materials and methods:
Patients with locally advanced oropharyngeal cancer treated to 70 Gy with concurrent chemoradiation (CCRT) on TomoTherapy® who underwent re-planning during the treatment were eligible. Survival and prognostic factors were evaluated with Kaplan–Meier and Cox proportional hazards, two-side p-value <0·05 significant.
Forty-two patients were identified with Stage III (n = 5), IVA (n = 34) and IVB (n = 3) [AJCC 7th] disease. Median re-planning dose was 40 Gy (14–60 Gy). Median change in mean total parotid dose was reduction of 1 Gy (range –7·5 Gy to +13·9 Gy). The volume of PTV70 and PTV60 receiving 99% of the prescribed (V99) dose was increased by 2·2% (–3·3 to +16·6%) and 1·9% (–11·5 to +12·6%) by re-planning. As a continuous variable, increasing per cent nodal regression was associated with the improved disease control in a multivariate model including stage, pack years smoking and human papilloma viral (HPV) status (HR: 0·85, 0·71–0·99, p = 0·05).
Adaptive planning generates a superior plan for the majority of patients, but there is modest overall parotid gland sparing.
A new fossil spider is described from the early Eocene (Ypresian) Palana Formation (54 to 57 Ma) at the Gurha opencast lignite mine, near Bikaner, western Rajasthan, India. It is the first report of a nonamber fossil spider from India. The fossil is referred to the modern genus Nephila Leach, 1815, but with hesitation because, while its habitus is similar to that genus, it lacks the behavioral synapomorphies that distinguish the genus.
The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.
This study examined the effect of the timing of administration of oseltamivir chemoprophylaxis for the control of influenza A H3N2 outbreaks among residents in long-term care facilities (LTCFs) in Manitoba, Canada, during the 2014–2015 influenza season.
A retrospective cohort study was conducted of all LTCF influenza A H3N2 outbreaks (n=94) using a hierarchical logistic regression analysis. The main independent variable was how many days passed between the start of the outbreak and commencement of oseltamivir chemoprophylaxis. The dependent variable was whether each person in the institution developed influenza-like illness (yes or no).
Delay of oseltamivir chemoprophylaxis was associated with increased odds of infection in both univariate (t=5·41; df=51; P<·0001) and multivariable analyses (t=6·04; df=49; P<·0001) with an adjusted odds ratio of 1.3 (95% confidence interval [CI], 1·2–1·5) per day for influenza A H3N2.
The sooner chemoprophylaxis is initiated, the lower the odds of secondary infection with influenza in LTCFs during outbreaks caused by influenza A H3N2 in Manitoba. For every day that passed from the start of the outbreak to the initiation of oseltamivir, the odds of a resident at risk of infection in the facility developing symptomatic infection increased by 33%.
OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.
The appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available.
As part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals' understanding of the ATT, and its impact on clinical practice.
Forty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process.
We found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient's age rather than diagnosis. The ATT has had little impact on clinical practice.
Our findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended.
Soft X-ray spectro-tomography provides three-dimensional (3D) chemical mapping based on natural X-ray absorption properties. Since radiation damage is intrinsic to X-ray absorption, it is important to find ways to maximize signal within a given dose. For tomography, using the smallest number of tilt series images that gives a faithful reconstruction is one such method. Compressed sensing (CS) methods have relatively recently been applied to tomographic reconstruction algorithms, providing faithful 3D reconstructions with a much smaller number of projection images than when conventional reconstruction methods are used. Here, CS is applied in the context of scanning transmission X-ray microscopy tomography. Reconstructions by weighted back-projection, the simultaneous iterative reconstruction technique, and CS are compared. The effects of varying tilt angle increment and angular range for the tomographic reconstructions are examined. Optimization of the regularization parameter in the CS reconstruction is explored and discussed. The comparisons show that CS can provide improved reconstruction fidelity relative to weighted back-projection and simultaneous iterative reconstruction techniques, with increasingly pronounced advantages as the angular sampling is reduced. In particular, missing wedge artifacts are significantly reduced and there is enhanced recovery of sharp edges. Examples of using CS for low-dose scanning transmission X-ray microscopy spectroscopic tomography are presented.
The mean delay for bipolar disorder diagnosis is 10 years. Identification of patients with previous hypomania is challenging, sometimes resulting in misdiagnosis. The aims of this study were: (a) to estimate the proportion of primary care patients with depression currently taking antidepressants who have undiagnosed bipolar disorder and (b) to compare a brief 3-item manic features questionnaire with the Hypomania Checklist (HCL-13). The sample comprised patients with a recorded diagnosis of depression, either on long-term antidepressant therapy or with previous multiple courses of antidepressants.
Of 149 participants assessed, 24 (16.1%) satisfied criteria for bipolar disorder. Areas under the curve (AUC) for the 3-item questionnaire and the HCL-13 were similar (0.79 and 0.72, respectively) but positive predictive values (PPV) were low.
Bipolar disorder may be underdiagnosed in primary care. A 3-item questionnaire could be used by general practitioners to screen for bipolar disorder in their patients with depression.
Infinite series are an important topic in mathematical analysis and convergence is the most crucial concept in the theory of infinite series. The speed at which the sequence of the partial sums of a series approaches its limiting sum has been a subject of investigation for many a mathematician. Euler , Kummer  and Markoff  all developed techniques for accelerating the convergence of slowly converging series. Euler's method only works for alternating series, Kummer's and Markoff's are suitable for general series with a special form.
Gosper  illustrates how the rate of convergence of infinite series can be accelerated by a suitable splitting of each term into two parts and then combining the second part of the n th term with the first part of n + 1 th the term and leaving the first part of the first term. Repeated application of this process yields a new series which approaches 0 and the series of the left out first parts (‘orphans’) that converges faster than the original series.
The Transitions of Care from Child and Adolescent Mental Health Services to Adult Mental Health Services (TRACK) study was a multistage, multicentre study of adolescents' transitions between child and adult mental health services undertaken in England. We conducted a secondary analysis of the TRACK study data to investigate healthcare provision for young people (n = 64) with ongoing mental health needs, who were not transferred from child and adolescent mental health services (CAMHS) to adult mental health services mental health services (AMHS).
The most common outcomes were discharge to a general practitioner (GP; n =29) and ongoing care with CAMHS (n = 13), with little indication of use of third-sector organisations. Most of these young people had emotional/neurotic disorders (n = 31, 48.4%) and neurodevelopmental disorders (n = 15, 23.4%).
GPs and CAMHS are left with the responsibility for the continuing care of young people for whom no adult mental health service could be identified. GPs may not be able to offer the skilled ongoing care that these young people need. Equally, the inability to move them decreases the capacity of CAMHS to respond to new referrals and may leave some young people with only minimal support.
Early intervention services (EIS) comprise low-stigma, youth-friendly mental health teams for young people undergoing first-episode psychosis (FEP). Engaging with the family of the young person is central to EIS policy and practice.
By analysing carers' accounts of their daily lives and affective challenges during a relative's FEP against the background of wider research into EIS, this paper explores relationships between carers' experiences and EIS.
Semi-structured longitudinal interviews with 80 carers of young people with FEP treated through English EIS.
Our data suggest that EIS successfully aid carers to support their relatives, particularly through the provision of knowledge about psychosis and medications. However, paradoxical ramifications of these user-focused engagements also emerge; they risk leaving carers' emotions unacknowledged and compounding an existing lack of help-seeking.
By focusing on EIS's engagements with carers, this paper draws attention to an urgent broader question: as a continuing emphasis on care outside the clinic space places family members at the heart of the care of those with severe mental illness, we ask: who can, and should, support carers, and in what ways?
Tuberculosis (TB) researchers and clinicians, by virtue of the social disease they study, are drawn into an engagement with ways of understanding illness that extend beyond the strictly biomedical model. Primers on social science concepts directly relevant to TB, however, are lacking. The particularities of TB disease mean that certain social science concepts are more relevant than others. Concepts such as structural violence can seem complicated and off-putting. Other concepts, such as gender, can seem so familiar that they are left relatively unexplored. An intimate familiarity with the social dimensions of disease is valuable, particularly for infectious diseases, because the social model is an important complement to the biomedical model. This review article offers an important introduction to a selection of concepts directly relevant to TB from health sociology, medical anthropology and social cognitive theory. The article has pedagogical utility and also serves as a useful refresher for those researchers already engaged in this genre of work. The conceptual tools of health sociology, medical anthropology and social cognitive theory offer insightful ways to examine the social, historical and cultural dimensions of public health. By recognizing cultural experience as a central force shaping human interactions with the world, TB researchers and clinicians develop a more nuanced consideration of how health, illness and medical treatment are understood, interpreted and confronted.
The ITRACK study explored the process and predictors of transition between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) in the Republic of Ireland.
Following ethical approval, clinicians in each of Ireland’s four Health Service Executive (HSE) areas were contacted, informed about the study and were invited to participate. Clinicians identified all cases who had reached the transition boundary (i.e. upper age limit for that CAMHS team) between January and December 2010. Data were collected on clinical and socio-demographic details and factors that informed the decision to refer or not refer to the AMHS, and case notes were scrutinised to ascertain the extent of information exchanged between services during transition.
A total of 62 service users were identified as having crossed the transition boundary from nine CAMHS [HSE Dublin Mid-Leinster (n=40, 66%), HSE South (n=18, 30%), HSE West (n=2, 3%), HSE Dublin North (n=1, 2%)]. The most common diagnoses were attention deficit hyperactivity disorder (ADHD; n=19, 32%), mood disorders (n=16, 27%), psychosis (n=6, 10%) and eating disorders (n=5, 8%). Forty-seven (76%) of those identified were perceived by the CAMHS clinician to have an ‘on-going mental health service need’, and of these 15 (32%) were referred, 11 (23%) young people refused and 21 (45%) were not referred, with the majority (12, 57%) continuing with the CAMHS for more than a year beyond the transition boundary. Young people with psychosis were more likely to be referred [χ2 (2, 46)=8.96, p=0.02], and those with ADHD were less likely to be referred [χ2 (2, 45)=8.89, p=0.01]. Being prescribed medication was not associated with referral [χ2 (2, 45)=4.515, p=0.11]. In referred cases (n=15), there was documented evidence of consent in two cases (13.3%), inferred in another four (26.7%) and documented preparation for transition in eight (53.3%). Excellent written communication (100%) was not supported by face-to-face planning meetings (n=2, 13.3%), joint appointments (n=1, 6.7%) or telephone conversations (n=1, 6.7%) between corresponding clinicians.
Despite perceived on-going mental health (MH) service need, many young people are not being referred or are refusing referral to the AMHS, with those with ADHD being the most affected. CAMHS continue to offer on-going care past the transition boundary, which has resource implications. Further qualitative research is warranted to understand, in spite of perceived MH service need, the reason for non-referral by the CAMHS clinicians and refusal by the young person.