Quantitative Assessment of Desensitizing Agents in Occluding Dentine Tubules using Image Analysis

Previous in vitro studies assessing the tubule occluding properties of various desensitizing agents in the dentine disc model appear to provide only qualitative data. The aim of this study was to establish a reliable and reproducible system to evaluate the in vitro effectiveness of three desensitizing agents. Six selected fields from SEM negatives (magnification x1000; working distance 10mm) of test and control dentine disc specimens treated with the desensitizing agents (Butler Protect, Colgate FluoriGard (GelKam), Macleans Sensitive) were evaluated. Fields were assessed using a Quantimet 520 Image analysis system (Leica UK) and the data recorded included patent tubule area, mean tubule diameter, mean patent/field area and number of tubules per unit area. Comparison of test and control specimens indicated that differences in the number of tubules, patent area, width of tubules and percentage of patent areas can be assessed quantitatively Furthermore, this methodology also demonstrated differences between the tubule occluding properties of the selected desensitizing agents

Mom-I don't want to hear it: Brain response to maternal praise and criticism in adolescents with major depressive disorder

Recent research has implicated altered neural response to interpersonal feedback as an important factor in adolescent depression, with existing studies focusing on responses to feedback from virtual peers. We investigated whether depressed adolescents differed from healthy youth in neural response to social evaluative feedback from mothers. During neuroimaging, twenty adolescents in a current episode of major depressive disorder (MDD) and 28 healthy controls listened to previously recorded audio clips of their own mothers' praise, criticism and neutral comments. Whole-brain voxelwise analyses revealed that MDD youth, unlike controls, exhibited increased neural response to critical relative to neutral clips in the parahippocampal gyrus, an area involved in episodic memory encoding and retrieval. Depressed adolescents also showed a blunted response to maternal praise clips relative to neutral clips in the parahippocampal gyrus, as well as areas involved in reward and self-referential processing (i.e. Ventromedial prefrontal cortex, precuneus, and thalamus/caudate). Findings suggest that maternal criticism may be more strongly encoded or more strongly activated during memory retrieval related to previous autobiographical instances of negative feedback from mothers in depressed youth compared to healthy youth. Furthermore, depressed adolescents may fail to process the reward value and self-relevance of maternal praise

Description of the BRIGHTLIGHT cohort: the evaluation of teenage and young adult cancer services in England

Objective International recognition of the unique needs of young people with cancer is growing. Many countries have developed specialist age-appropriate cancer services believing them to be of value. In England, 13 specialist principal treatment centres (PTCs) deliver cancer care to young people. Despite this expansion of specialist care, systematic investigation of associated outcomes and costs has, to date, been lacking. The aim of this paper is to describe recruitment and baseline characteristics of the BRIGHTLIGHT cohort and the development of the bespoke measures of levels of care and disease severity, which will inform the evaluation of cancer services in England. Design Prospective, longitudinal, observational study. Setting Ninety-seven National Health Service hospitals in England. Participants A total of 1114 participants were recruited and diagnosed between July 2012 and December 2014: 55% (n=618) were men, mean age was 20.1 years (SD=3.3), most (86%) were white and most common diagnoses were lymphoma (31%), germ cell tumour (19%) and leukaemia (13%). Results At diagnosis, median quality of life score was significantly lower than a published control threshold (69.7 points); 40% had borderline to severe anxiety, and 21% had borderline to severe depression. There was minimal variation in other patient-reported outcomes according to age, diagnosis or severity of illness. Survival was lower in the cohort than for young people diagnosed during the same period who were not recruited (cumulative survival probability 4 years after diagnosis: 88% vs 92%). Conclusions Data collection was completed in March 2018. Longitudinal comparisons will determine outcomes and costs associated with access/exposure to PTCs. Findings will inform international intervention and policy initiatives to improve outcomes for young people with cancer

Scaling of Entanglement close to a Quantum Phase Transitions

In this Letter we discuss the entanglement near a quantum phase transition by analyzing the properties of the concurrence for a class of exactly solvable models in one dimension. We find that entanglement can be classified in the framework of scaling theory. Further, we reveal a profound difference between classical correlations and the non-local quantum correlation, entanglement: the correlation length diverges at the phase transition, whereas entanglement in general remains short ranged.Comment: 4 pages, 4 figures, revtex. Stylistic changes and format modifie

Emerging Concepts for Pelvic Organ Prolapse Surgery: What is Cure?

The objective of this review is to discuss emerging concepts in pelvic organ prolapse, in particular, “What is cure?” In a post-trial data analysis of the CARE (Colpopexy and Urinary Reduction Efforts) trial, treatment success varied tremendously depending on the definition used (19.2%–97.2%). Definitions that included the absence of vaginal bulge symptoms had the strongest relationships with the patients’ assessment of overall improvement and treatment success. As demonstrated by this study, there are several challenges in defining cure in prolapse surgery. Additionally, the symptoms of prolapse are variable. The degree of prolapse does not correlate directly with symptoms. There are many surgical approaches to pelvic organ prolapse. Multiple ways to quantify prolapse are used. There is a lack of standardized definition of cure. The data on prolapse surgery outcomes are heterogeneous. The goal of surgical repair is to return the pelvic organs to their original anatomic positions. Ideally, we have four main goals: no anatomic prolapse, no functional symptoms, patient satisfaction, and the avoidance of complications. The impact of transvaginal mesh requires thoughtful investigation. The driving force should be patient symptoms in defining cure of prolapse

Specialist cancer services for teenagers and young adults in England: BRIGHTLIGHT research programme

Background: When cancer occurs in teenagers and young adults, the impact is far beyond the physical disease and treatment burden. The effect on psychological, social, educational and other normal development can be profound. In addition, outcomes including improvements in survival and participation in clinical trials are poorer than in younger children and older adults with similar cancers. These unique circumstances have driven the development of care models specifically for teenagers and young adults with cancer, often focused on a dedicated purpose-designed patient environments supported by a multidisciplinary team with expertise in the needs of teenagers and young adults. In England, this is commissioned by NHS England and delivered through 13 principal treatment centres. There is a lack of evaluation that identifies the key components of specialist care for teenagers and young adults, and any improvement in outcomes and costs associated with it. / Objective: To determine whether or not specialist services for teenagers and young adults with cancer add value. / Design: A series of multiple-methods studies centred on a prospective longitudinal cohort of teenagers and young adults who were newly diagnosed with cancer. / Settings: Multiple settings, including an international Delphi study of health-care professionals, qualitative observation in specialist services for teenagers and young adults, and NHS trusts. / Participants: A total of 158 international teenage and young adult experts, 42 health-care professionals from across England, 1143 teenagers and young adults, and 518 caregivers. / Main outcome measures: The main outcomes were specific to each project: key areas of competence for the Delphi survey; culture of teenagers and young adults care in the case study; and unmet needs from the caregiver survey. The primary outcome for the cohort participants was quality of life and the cost to the NHS and patients in the health economic evaluation. / Data sources: Multiple sources were used, including responses from health-care professionals through a Delphi survey and face-to-face interviews, interview data from teenagers and young adults, the BRIGHTLIGHT survey to collect patient-reported data, patient-completed cost records, hospital clinical records, routinely collected NHS data and responses from primary caregivers. / Results: Competencies associated with specialist care for teenagers and young adults were identified from a Delphi study. The key to developing a culture of teenage and young adult care was time and commitment. An exposure variable, the teenagers and young adults Cancer Specialism Scale, was derived, allowing categorisation of patients to three groups, which were defined by the time spent in a principal treatment centre: SOME (some care in a principal treatment centre for teenagers and young adults, and the rest of their care in either a children’s or an adult cancer unit), ALL (all care in a principal treatment centre for teenagers and young adults) or NONE (no care in a principal treatment centre for teenagers and young adults). The cohort study showed that the NONE group was associated with superior quality of life, survival and health status from 6 months to 3 years after diagnosis. The ALL group was associated with faster rates of quality-of-life improvement from 6 months to 3 years after diagnosis. The SOME group was associated with poorer quality of life and slower improvement in quality of life over time. Economic analysis revealed that NHS costs and travel costs were similar between the NONE and ALL groups. The ALL group had greater out-of-pocket expenses, and the SOME group was associated with greater NHS costs and greater expense for patients. However, if caregivers had access to a principal treatment centre for teenagers and young adults (i.e. in the ALL or SOME groups), then they had fewer unmet support and information needs. / Limitations: Our definition of exposure to specialist care using Hospital Episode Statistics-determined time spent in hospital was insufficient to capture the detail of episodes or account for the variation in specialist services. Quality of life was measured first at 6 months, but an earlier measure may have shown different baselines. / Conclusions: We could not determine the added value of specialist cancer care for teenagers and young adults as defined using the teenage and young adult Cancer Specialism Scale and using quality of life as a primary end point. A group of patients (i.e. those defined as the SOME group) appeared to be less advantaged across a range of outcomes. There was variation in the extent to which principal treatment centres for teenagers and young adults were established, and the case study indicated that the culture of teenagers and young adults care required time to develop and embed. It will therefore be important to establish whether or not the evolution in services since 2012–14, when the cohort was recruited, improves quality of life and other patient-reported and clinical outcomes. / Future work: A determination of whether or not the SOME group has similar or improved quality of life and other patient-reported and clinical outcomes in current teenage and young adult service delivery is essential if principal treatment centres for teenagers and young adults are being commissioned to provide ‘joint care’ models with other providers. / Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 12. See the NIHR Journals Library website for further project information

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

In situ Biological Dose Mapping Estimates the Radiation Burden Delivered to ‘Spared’ Tissue between Synchrotron X-Ray Microbeam Radiotherapy Tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to ‘spared’ tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30–40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies