"There should be one spot that you can go:" BRCA mutation carriers' perspectives on cancer risk management and a hereditary cancer registry.

Individuals who carry BRCA1 or BRCA2 pathogenic variants are recommended to have extensive cancer prevention screening and risk-reducing surgeries. Uptake of these recommendations is variable, and there remains room for improvement in the risk management of BRCA carriers. This paper explores female BRCA carriers' experiences with the current model of care and their perspectives on (and interest in) an inherited cancer registry. Findings can inform the development of a dedicated high-risk screening and management program for these patients. Quantitative and qualitative data were gathered through a provincial descriptive survey and semi-structured qualitative interviews to assess BRCA carriers' opinions toward risk management services in the province of Newfoundland and Labrador (NL), Canada. Survey (n = 69) and interview data (n = 15) revealed continuity and coordination challenges with the current system of care of high-risk individuals. Respondents suggested an inherited cancer registry would help identify high-risk individuals and provide a centralized system of risk management for identified carriers. Respondents identified concerns about the privacy of their registry data, including who could access it. Findings suggest BRCA carriers see great value in an inherited cancer registry. Specifically, participants noted it could provide a centralized system to help improve the coordination of burdensome, life-long risk management. Important patient concerns about protecting their privacy and their health data confidentiality must be addressed in patient and public information and informed consent documents about a registry.

Tradeoffs and synergies in wetland multifunctionality: A scaling issue.

Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.

Blood Indices In Adult Acute Burn: A Window Into Milieu Interieur - The Future Biomarkers?

Optimal treatment of sepsis in burned patients depends on early diagnosis and includes prompt administration of antimicrobials as well as management of hemodynamic alterations and other organ dysfunctions. The role of red blood cell distribution width (RDW) and platelet indices in prognosticating and identifying sepsis in acute burn patients is studied. This study was done as a prospective study over 18 months, including patients in the age group >18 or <60 years, with burns >20% and <70% TBSA, burn time to resuscitation time 24 hours or less and with thermal and scald burns. Data of 157 patients were analyzed and the following observations were made. The mean age of the study population was 31.36 years (18-59 years). RDW values were higher in the non-survivor group. Platelet count and plateletcrit were higher in the survivor group and the no sepsis group. Positive rising trends of platelet count and plateletcrit were seen in the survivor group. Day 1, 3, 7 values of RDW, platelet count and plateletcrit were significant in determining the outcome of the patient on mortality and sepsis related morbidity of the patient. RDW, platelet count and plateletcrit in combination can predict mortality and sepsis as early as the third day, thus giving a clinical advantage of initiating targeted treatment to the at-risk burn population before sepsis is detected clinically. This could better the outcomes in treatment of burn patients.

Le traitement optimal du sepsis des brûlés dépend d'un diagnostic précoce et d'une antibiothérapie rapide ainsi que de la prise en charge du choc et des défaillances d'organe. Nous rapportons ici l'intérêt de l'index de distribution des globules rouges (IDGR) et d'indices plaquettaires dans le diagnostic et le pronostic du sepsis chez les brûlés. Nous présentons une étude prospective réalisée auprès de 157 patients de 18 à 60 ans (moyenne 31,36), brûlés sur 20 à 70% de SCT, pris en charge dans les 24 h après brûlure par flamme ou ébouillantement, recrutés pendant 18 mois. L'IDGR était plus élevés chez les patients décédés, quand la numération (NP) et le volume plaquettaire total (VPT) étaient plus élevés chez les survivants et les patients non infectés. La cinétique d'augmentation de NP et de VPT entre J1, J3 et J7 permettait de prédire sepsis et mortalité. Ainsi, IDGR, NP et VPT permettent de prédire la survenue de sepsis et un décès dès J3, permettant de débuter un traitement avant la survenue d'une infection, ce qui pourrait améliorer le devenir des brûlés.

A Risk Score Model for Locoregional Recurrence Following Upfront Surgery for Pancreatic Adenocarcinoma: Implications for Adjuvant Therapy.

AIMS: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF. MATERIALS AND METHODS: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF. RESULTS: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001). CONCLUSION: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.

Dysautonomia as the Presenting Symptom in Anti-Muscle-Specific Kinase Antibody Myasthenia Gravis.

In an minority of Myasthenia Gravis (MG) patients, the autoantibodies bind to muscle-specific kinase (MUSK). These MuSK antibody-mediated MG (MuSK MG) patients are not only immunologically distinct, but also have different characteristic clinical features. Dysautonomia in MG is rarely reported. We present a MuSK MG patient who suffered from life-threatening autonomic dysfunction. MuSK MG should be considered in the differential diagnosis in cases of unclarified dysautonomia, given the potential for treatment in those cases.

Across and within breed differences in the relationship between packed cell volume and fecal egg count in growing meat goat and hair sheep males naturally and artificially infected with gastrointestinal nematodes.

The relationship between packed cell volume (PCV) and fecal egg count (FEC) in different breeds of meat goats and hair sheep infected with gastrointestinal nematodes, including Haemonchus contortus, was characterized. Growing males from eight commercial and two research farms (one Kiko, Spanish, Dorper, and St. Croix; three Boer; four Katahdin) in the southcentral United States were evaluated in a central performance test with ad libitum intake of a 50% concentrate pelleted diet. There were 84 Boer, 55 Kiko, and 57 Spanish goats and 52 Dorper, 129 Katahdin, and 49 St. Croix sheep. During adaptation, animals were dewormed then dosed with 10,000 infective H. contortus larvae. PCV and FEC were determined before deworming (i.e., natural infection potentially with multiple internal parasites) and 21, 28, 35, 42, and 49 days after artificial infection. Effects of species, breed, and year were analyzed with mixed effects models including day of sampling post dosing as a repeated measure and FEC and FEC × breed as covariates. Moreover, differences in correlation coefficients between PCV and logarithmic FEC (lnFEC) among species, breed, year, and day of sampling were evaluated. Breed affected (P ≤ 0.001) PCV in goats (24.8, 27.2, and 26.0% for Boer, Kiko, and Spanish, respectively; SEM = 0.42) and sheep (29.8, 26.7, and 31.0% for Dorper, Katahdin, and St. Croix, respectively; SEM = 0.28). There were effects of FEC × breed (P ≤ 0.029) on PCV for Boer, Kiko, Dorper, Katahdin, and St. Croix (-0.31, -0.33, -0.46, -0.46, and - 0.49% per 1000 eggs, respectively) but not for Spanish goats (P = 0.451). With all data, PCV and lnFEC with natural infection were highly correlated (P < 0.001) for Boer and Kiko goats and Dorper and Katahdin sheep (r = -0.59, -0.67, -0.77, and - 0.84, respectively) but not for Spanish goats or St. Croix sheep (P ≥ 0.323). Correlation coefficients for artificial infection with H. contortus were significant (P ≤ 0.002) except for Spanish goats, although values were lower (-0.40, -0.21, -0.23, -0.47, and - 0.28 for Boer, Kiko, Dorper, Katahdin, and St. Croix, respectively) compared with natural infection. In conclusion, PCV was not related to FEC in Spanish goats infected either naturally or artificially, and the nature of the relationship varied among breeds of goats and sheep. Based on the magnitude of the FEC × breed coefficient, sheep incurred a relatively greater reduction in PCV as FEC increased, and correlation coefficients indicate stronger relationships with natural than artificial infection.

Contrasting Some Differences in Managing Advanced Unresectable Hepatocellular Carcinoma Between the East and the West.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, although its aetiologies vary significantly between the East and the West. About a half of HCC cases present with advanced unresectable HCC at the time of diagnosis, leading to a worse prognosis. Over the past 20 years, the treatment paradigm for advanced unresectable HCC has shifted from an entirely palliative approach to a multidisciplinary treatment, with continuous reassessment and possible repeat treatment attributed to the advent of novel and improved local, regional and systemic therapeutic options, contributed by both the East and the West. An individualised treatment plan should be determined for each patient, as there can be substantial differences in the decision-making and treatment response to the same treatment for different patients and different patient populations. This review provides a summary of the recent advances in management and compares Eastern and Western strategies for HCC.

The discrimination of geoforensic trace material from close proximity locations by organic profiling using HPLC and plant wax marker analysis by GC.

There is a need to develop a wider empirical research base to expand the scope for utilising the organic fraction of soil in forensic geoscience, and to demonstrate the capability of the analytical techniques used in forensic geoscience to discriminate samples at close proximity locations. The determination of wax markers from soil samples by GC analysis has been used extensively in court and is known to be effective in discriminating samples from different land use types. A new HPLC method for the analysis of the organic fraction of forensic sediment samples has also been shown recently to add value in conjunction with existing inorganic techniques for the discrimination of samples derived from close proximity locations. This study compares the ability of these two organic techniques to discriminate samples derived from close proximity locations and finds the GC technique to provide good discrimination at this scale, providing quantification of known compounds, whilst the HPLC technique offered a shorter and simpler sample preparation method and provided very good discrimination between groups of samples of different provenance in most cases. The use of both data sets together gave further improved accuracy rates in some cases, suggesting that a combined organic approach can provide added benefits in certain case scenarios and crime reconstruction contexts.

Knowing about you: eliciting dimensions of personhood within tuberculosis care.

BACKGROUND: Knowing someone with tuberculosis (TB) as a person, rather than defining them by their illness, is part of recognising their dignity and unique individuality, and a requirement for effective care. OBJECTIVE: An adaptation of the Patient Dignity Question (PDQ) was formalised for persons receiving treatment for active TB or latent tuberculous infection (LTBI), and its impact was evaluated for both the person and health care providers (HCPs). DESIGN: Individuals with active TB or LTBI receiving treatment in Winnipeg, MB, Canada, were asked the PDQ as part of routine care. Patients and HCPs were subsequently invited to evaluate the application of the PDQ. RESULTS: Of the 58 participants who responded to the PDQ, 97% felt both that it was important to ask about them as an individual, and that the PDQ should be asked of all patients, while 55% thought it made a difference to their care. Thirty-eight per cent of HCPs said they learned something new about their patient, and 31% said it influenced their sense of connectedness with and sense of empathy for patients, as well as their personal satisfaction in providing care. CONCLUSION: Formalising a dignity question as part of person-centred care provides a mechanism to create a respectful environment that is caring of the most marginalised who carry the burden of TB.

The identification of markers for Geoforensic HPLC profiling at close proximity sites.

Soil is a highly transferable source of trace physical material that is both persistent in the environment and varied in composition. This inherent variability can provide useful information to determine the geographical origin of a questioned sample or when comparing and excluding samples, since the composition of soil is dependent on geographical factors such as climate, bedrock geology and land use. Previous studies have limited forensic relevance due to the requirement for large sample amounts and unrealistic differences between the land use and geographical location of the sample sites. In addition the philosophical differences between the disciplines of earth sciences, for which most analytical techniques have been designed, and forensic sciences, particularly with regard to sample preparation and data interpretation have not been fully considered. This study presents an enhanced technique for the analysis of organic components of geoforensic samples by improving the sample preparation and data analysis strategies used in previous research into the analysis of soil samples by high performance liquid chromatography (HPLC). This study provides two alternative sets of marker peaks to generate HPLC profiles which allow both easy visual comparison of samples and the correct assignment of 100% of the samples to their location of origin when discriminating between locations of interest in multivariate statistical analyses. This technique thereby offers an independent form of analysis that is complementary to inorganic geoforensic techniques and offers an easily accessible method for discriminating between close proximity forensically relevant locations.

Search for Neutrinoless Quadruple-ß Decay of

We report the results of a first experimental search for lepton number violation by four units in the neutrinoless quadruple-ß decay of ^{150}Nd using a total exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane Underground Laboratory. We find no evidence of this decay and set lower limits on the half-life in the range T_{1/2}>(1.1-3.2)×10^{21} yr at the 90% C.L., depending on the model used for the kinematic distributions of the emitted electrons.

Degenerative Encephalopathy in Nova Scotia Duck Tolling Retrievers Presenting with a Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Neurodegenerative diseases are a heterogeneous group of disorders characterized by loss of neurons and are commonly associated with a genetic mutation. HYPOTHESIS/OBJECTIVES: To characterize the clinical and histopathological features of a novel degenerative neurological disease affecting the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs). ANIMALS: Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and rapid eye movement sleep behavior disorder. METHODS: Case series review. RESULTS: Clinical signs of neurological dysfunction began between 2 months and 5 years of age and were progressive in nature. They were characterized by episodes of marked movements during sleep, increased anxiety, noise phobia, and gait abnormalities. Magnetic resonance imaging documented symmetrical, progressively increasing, T2-weighted image intensity, predominantly within the caudate nuclei, consistent with necrosis secondary to gray matter degeneration. Abnormalities were not detected on clinicopathological analysis of blood and cerebrospinal fluid, infectious disease screening or urine metabolite screening in most cases. Postmortem examination of brain tissue identified symmetrical malacia of the caudate nuclei and axonal dystrophy within the brainstem and spinal cord. Genealogical analysis supports an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: A degenerative encephalopathy was identified in young adult NSDTRs consistent with a hereditary disease. The prognosis is guarded due to the progressive nature of the disease, which is minimally responsive to empirical treatment.

The Overseas Registration Examination of the General Dental Council.

The Overseas Registration Examination is a route to entry to the UK Dentists Register for dentists who have qualified outside the European Economic Area. The role of the examination is to protect the public by ensuring that such dentists meet minimum standards of competence. Candidates invest considerable time and resource in attempting the examination. For these reasons it is essential that the examination is both robust and fair. This paper describes the fundamental principles of assessment underpinning the design of the examination and the steps taken by the General Dental Council's ORE Advisory Group to assure its ongoing quality.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats.

In certain forms of nerve injury and inflammation, noradrenaline augments pain via actions on up-regulated α1-adrenoceptors (α1-ARs). The aim of this study was to use immunohistochemistry to examine α1-AR expression on peripheral neurons, cutaneous blood vessels and keratinocytes after distal tibia fracture and cast immobilization, a model of complex regional pain syndrome type 1. We hypothesized that there would be increased α1-AR expression on neurons and keratinocytes in the injured limb in comparison to the contralateral unaffected limb after distal tibia fracture, in association with inflammatory changes and pain. α1-AR expression was increased on plantar keratinocytes, dermal blood vessels and peripheral nerve fibers at 16weeks after injury both in the fractured and contralateral uninjured limb. Similar changes were seen in controls whose limb had been immobilized in a cast for 4weeks but not fractured. Neurofilament 200 (NF200), a marker of myelinated neurons, and calcitonin gene-related peptide (CGRP), a neuropeptide involved in neuro-inflammatory signaling, decreased 4weeks after fracture and casting but then increased at the 16-week time point. As some of these changes were also detected in the contralateral hind limb, they probably were triggered by a systemic response to fracture and casting. Soon after the cast was removed, intraplantar injections of the α1-AR antagonist prazosin released local vasoconstrictor tone but had no effect on pain behaviors. However, systemic injection of prazosin inhibited behavioral signs of pain, suggesting that fracture and/or casting triggered an up-regulation of α1-ARs in central nociceptive pathways that augmented pain. Together, these findings indicate that α1-AR expression increases in the hind limbs after distal tibia fracture and cast immobilization. However, these peripheral increases do not contribute directly to residual pain.

Metabolic syndrome-related hepatocellular carcinoma treated by volumetric modulated arc therapy.

Hepatocellular carcinoma (hcc) is a leading cause of cancer mortality, and its incidence is increasing in developed countries. Risk factors include cirrhosis from viral hepatitis or alcohol abuse. Metabolic syndrome is a newly recognized, but important, risk factor that is likely contributing to the increased incidence of hcc. Surgery is the therapy of choice for hcc, but local therapies are often contraindicated, usually because of advanced disease or comorbid conditions such as cardiac disease (which is associated with metabolic syndrome). Current radiation therapy techniques such as stereotactic body radiotherapy allow for treatment plans that highly conform to the target and provide excellent sparing of normal structures. Radiation therapy is emerging as a viable option in patients not eligible for surgery or other locoregional therapies. Here, we report a case of a large hcc presenting in a patient with metabolic syndrome without significant alcohol history or biochemical liver dysfunction. The patient was not a candidate for locoregional therapies because of cardiac and renal comorbidities typical of patients experiencing the long-term sequelae of metabolic syndrome. Treatment using an arc-based volumetric-modulated arc therapy technique allowed for the highest dose of radiation to be delivered to the tumour while the peripheral radiation dose was minimized. A complete local response was confirmed by computed tomography imaging 21 months after treatment completion.