Diagnosis delay of breast cancer and its associated factors in Malaysian women

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the leading cause of cancer mortality among women in Malaysia. Delayed diagnosis is preventable and has major effects on patients' prognosis and survival. The objectives of our study were to identify the magnitude of delayed diagnosis and its associated factors in women with breast cancer in Malaysia.</p> <p>Methods</p> <p>This study had a cross-sectional design. Respondents had histologically confirmed breast cancer and were registered at five medical centres between 2005 and 2007. All breast cancer patients who attended hospital clinics at the East Coast were included. Patients at Kuala Lumpur hospitals were selected by systematic sampling. A standardised questionnaire was developed to interview respondents. We measured the time from the first recognition of symptoms to the first general practitioners' consultation and to the histological diagnosis of breast cancer. Diagnosis delay was defined when there was more than 6 months from the recognition of symptoms to the histological diagnosis. Multiple logistic regression was used for analysis.</p> <p>Results</p> <p>In total, 328 respondents were included. The mean (standard deviation) age was 47.9 (9.4) years. Most respondents were of Malay ethnicity, were married housewives with a median family income of RM1500 a month. Most respondents had ductal carcinoma (89.3%) and the stage distribution was as follows: 5.2% stage I, 38.7% stage II, 44.8% stage III and 11.3% stage IV. The median time to consultation was 2 months and the median time to diagnosis was 5.5 months. The frequency of diagnosis delay of more than 3 months was 72.6% and delay of more than 6 months occurred in 45.5% of the cases. The factors associated with diagnosis delay included the use of alternative therapy (odds ratio (OR) 1.77; 95% confidence interval (CI): 1.06, 2.94), breast ulcer (OR 5.71; 95% CI: 1.59, 20.47), palpable axillary lymph nodes (OR 2.19; 95% CI: 1.23, 3.90), false-negative diagnostic test (OR 5.32; 95% CI: 2.32, 12.21), non-cancer interpretation (OR 1.68; 95% CI: 1.01, 2.78) and negative attitude toward treatment (OR 2.09; 95% CI: 1.15, 3.82).</p> <p>Conclusions</p> <p>Delays in consultation and diagnosis are serious problems in Malaysia. Diagnosis delay was influenced by complex interactions between many factors. Breast awareness and education are required to promote early detection, diagnosis and treatment before the tumours enlarge and metastasis.</p

The National Pediatric Surgery Simulation Program in France: A tool to develop resident training in pediatric surgery

BACKGROUND/PURPOSE: To implement resident curriculum in France based on theoretical teaching and bed side training, the national council known as the "Collège Hospitalier et Universitaire de Chirurgie Pédiatrique" examined the relevance and feasibility of systematically introducing simulation program in the pediatric surgery resident training. MATERIAL AND METHODS: A national simulation training program was developed and took place in a 2-day session organized in 7 simulation centers in France. The program included technical (laparoscopic/suturing technique on low-fidelity models) and nontechnical (6 scenarios for standardized consultation, and a team work scenario based on errors prevention in the operative room) skills. Evaluation of the program (Likert scale from 1 (bad) to 5 (excellent) and notation on 20 points) concerned trainees and trainers. RESULTS: 40 residents (95% of all pediatric surgery French residents) attended with a ratio of trainees/trainer of ½. The training objectives earned a score of 4.46/5. The pedagogical value of the seminar scored 4.7/5, teaching quality 17.95/20, and the overall seminar score was 17.35/20. CONCLUSION: This program, unique nationally, was assessed very favorably by the participating residents and by the involved trainers. To our knowledge, it represents the first mandatory national simulation training program included within a surgical training model. LEVEL OF EVIDENCE: Level IV

Low back pain and association with whole body vibration among military armoured vehicle drivers in Malaysia.

A cross sectional study was conducted among military armoured vehicle drivers in the two largest mechanized battalions with the objective to determine the prevalence of low back pain (LBP), and its association with whole body vibration (WBV) and other associated factors. A self-administered questionnaire and Human Vibration Meter were used in this study. A total of 159 respondents participated in this study and 102 (64.2%) of them were subjected to WBV measurement. One-hundred-and-seventeen respondents complained of LBP for the past 12 months giving a prevalence of 73.6%. The prevalence of LBP among tracked armoured vehicle drivers was higher (81.7%) as compared to wheeled armoured vehicle drivers (67.0%). The mean acceleration at Z-axis in tracked armoured vehicles (1.09 ± 0.26 ms-2) and wheeled armoured vehicles (0.33 ± 0.07 ms-2) were the dominant vibration directions. The mean estimated vibration dose value (eVDV) for eight-hour daily exposure at Z-axis (19.86 ± 4.72 ms-1.75) in tracked armoured vehicles showed the highest estimation. Based on the European Vibration Directive (2002), the mean eVDV at Z-axis in tracked armoured vehicles exceeded exposure action value (EAV) (> 9.1 ms-1.75), but did not exceed exposure limit value (ELV) (<21.0 ms-1.75). Logistic regression analysis revealed that only driving in forward bending sitting posture (OR=3.63, 95% CI 1.06-12.42) and WBV exposure at X-axis (OR=1.94, 95% CI 1.02-3.69) were significant risk factors to LBP. Preventive measures should be implemented to minimize risk of WBV and to improve ergonomic postures among drivers

Estimating instantaneous sea-ice dynamics from space using the bi-static radar measurements of Earth Explorer 10 candidate Harmony

This article describes the observation techniques and suggests processing methods to estimate dynamical sea-ice parameters from data of the Earth Explorer 10 candidate Harmony. The two Harmony satellites will fly in a reconfigurable formation with Sentinel-1D. Both will be equipped with a multi-angle thermal infrared sensor and a passive radar receiver, which receives the reflected Sentinel-1D signals using two antennas. During the lifetime of the mission, two different formations will be flown. In the stereo formation, the Harmony satellites will fly approximately 300 km in front and behind Sentinel-1, which allows for the estimation of instantaneous sea-ice drift vectors. We demonstrate that the addition of instantaneous sea-ice drift estimates on top of the daily integrated values from feature tracking have benefits in terms of interpretation, sampling and resolution. The wide-swath instantaneous drift observations of Harmony also help to put high-temporal-resolution instantaneous buoy observations into a spatial context. Additionally, it allows for the extraction of deformation parameters, such as shear and divergence. As a result, Harmony's data will help to improve sea-ice statistics and parametrizations to constrain sea-ice models. In the cross-track interferometry (XTI) mode, Harmony's satellites will fly in close formation with an XTI baseline to be able to estimate surface elevations. This will allow for improved estimates of sea-ice volume and also enables the retrieval of full, two-dimensional swell-wave spectra in sea-ice-covered regions without any gaps. In stereo formation, the line-of-sight diversity allows the inference of swell properties in both directions using traditional velocity bunching approaches. In XTI mode, Harmony's phase differences are only sensitive to the ground-range direction swell. To fully recover two-dimensional swell-wave spectra, a synergy between XTI height spectra and intensity spectra is required. If selected, the Harmony mission will be launched in 2028

CeLAND: search for a 4th light neutrino state with a 3 PBq 144Ce-144Pr electron antineutrino generator in KamLAND

The reactor neutrino and gallium anomalies can be tested with a 3-4 PBq (75-100 kCi scale) 144Ce-144Pr antineutrino beta-source deployed at the center or next to a large low-background liquid scintillator detector. The antineutrino generator will be produced by the Russian reprocessing plant PA Mayak as early as 2014, transported to Japan, and deployed in the Kamioka Liquid Scintillator Anti-Neutrino Detector (KamLAND) as early as 2015. KamLAND's 13 m diameter target volume provides a suitable environment to measure the energy and position dependence of the detected neutrino flux. A characteristic oscillation pattern would be visible for a baseline of about 10 m or less, providing a very clean signal of neutrino disappearance into a yet-unknown, sterile neutrino state. This will provide a comprehensive test of the electron dissaperance neutrino anomalies and could lead to the discovery of a 4th neutrino state for Delta_m^2 > 0.1 eV^2 and sin^2(2theta) > 0.05.Comment: 67 pages, 50 figures. Th. Lasserre thanks the European Research Council for support under the Starting Grant StG-30718

The 2017 reversal of the Beaufort Gyre: Can dynamic thickening of a seasonal ice cover during a reversal limit summer ice melt in the Beaufort Sea?

During winter 2017 the semi‐permanent Beaufort High collapsed and the anticyclonic Beaufort Gyre reversed. The reversal drove eastward ice motion through the Western Arctic, causing sea ice to converge against Banks Island, and halted the circulation of multiyear sea ice via the gyre, preventing its replenishment in the Beaufort Sea. Prior to the reversal, an anomalously thin seasonal ice cover had formed in the Beaufort following ice‐free conditions during September 2016. With the onset of the reversal in January 2017, convergence drove uncharacteristic dynamic thickening during winter. By the end of March, despite seasonal ice comprising 97% of the ice cover, the reversal created the thickest, roughest and most voluminous regional ice cover of the CryoSat‐2 record. Within the Beaufort Sea, previous work has shown that winter ice export can precondition the region for increased summer ice melt, but that a short reversal during April 2013 contributed to a reduction in summer ice loss. Hence the deformed ice cover at the end of winter 2017 could be expected to limit summer melt. In spite of this, the Beaufort ice cover fell to its fourth lowest September area as the gyre re‐established during April and divergent ice drift broke up the pack, negating the reversal's earlier preconditioning. Our work highlights that dynamic winter thickening of a regional sea ice cover, for instance during a gyre reversal, offers the potential to limit summer ice loss, but that dynamic forcing during spring dictates whether this conditioning carries through to the melt season

Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

<p>Abstract</p> <p>Background</p> <p>Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control.</p> <p>Methods</p> <p>We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL).</p> <p>Results</p> <p>The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05).</p> <p>Conclusions</p> <p>There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.</p

JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition

Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617Fand mutant IDH1R132Hor Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617FIdh2R140Q–mutant MPNs were sensitive to small-molecule inhibition of IDH. Combined inhibition of JAK2 and IDH2 normalized the stem and progenitor cell compartments in the murine model and reduced disease burden to a greater extent than was seen with JAK inhibition alone. In addition, combined JAK2 and IDH2 inhibitor treatment also reversed aberrant gene expression in MPN stem cells and reversed the metabolite perturbations induced by concurrent JAK2 and IDH2 mutations. Combined JAK2 and IDH2 inhibitor therapy also showed cooperative efficacy in cells from MPN patients with both JAK2mutand IDH2mutmutations. Taken together, these data suggest that combined JAK and IDH inhibition May offer a therapeutic advantage in this high-risk MPN subtype.Damon Runyon Cancer Research Foundation (DRG-2241-15)Howard Hughes Medical Institute (Faculty Scholars Award)Stand Up To CancerNational Cancer Institute (U.S.) (P50CA165962)National Cancer Institute (U.S.) (P30CA14051)Koch Institute for Integrative Cancer Research ( Dana-Farber Harvard Cancer Center Bridge Project)Leukemia & Lymphoma Society of America. Specialized Center of Research (SCOR) ProgramNational Institutes of Health (U.S.) (grant U54OD020355-01)National Institutes of Health (U.S.) (grant NCI R01CA172636)National Institutes of Health (U.S.) (grant R35CA197594)National Cancer Institute (U.S.) (Cancer Center Support Grant (P30 CA008747)

Biological strategy for the fabrication of highly ordered aragonite helices: The microstructure of the cavolinioidean gastropods

The Cavolinioidea are planktonic gastropods which construct their shells with the so-called aragonitic helical fibrous microstructure, consisting of a highly ordered arrangement of helically coiled interlocking continuous crystalline aragonite fibres. Our study reveals that, despite the high and continuous degree of interlocking between fibres, every fibre has a differentiated organic-rich thin external band, which is never invaded by neighbouring fibres. In this way, fibres avoid extinction. These intra-fibre organic-rich bands appear on the growth surface of the shell as minuscule elevations, which have to be secreted differentially by the outer mantle cells. We propose that, as the shell thickens during mineralization, fibre secretion proceeds by a mechanism of contact recognition and displacement of the tips along circular trajectories by the cells of the outer mantle surface. Given the sizes of the tips, this mechanism has to operate at the subcellular level. Accordingly, the fabrication of the helical microstructure is under strict biological control. This mechanism of fibre-by-fibre fabrication by the mantle cells is unlike that any other shell microstructure.Funding was provided by Research Projects CGL2013-48247-P of the Spanish Ministerio de Economía y Competitividad (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER), and P10-RNM6433 of the Andalusian Consejería de Economía, Investigación, Ciencia y Empleo, of the Junta de Andalucía, and by the Research Group RNM363 (latter Institution)

A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.

Most MPN patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells we developed a novel strategy (KISMET) which utilises the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional siRNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the MAPK pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by MPL-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34-cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34+ progenitors. These data link aberrant MAPK activation to the MPN phenotype and identify it as a potential therapeutic target in CALR-mutant positive MPNs.Leukemia accepted article preview online, 14 October 2016. doi:10.1038/leu.2016.280.Work in the Green lab is supported by Leukemia and Lymphoma Research, Cancer Research UK, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre and the Leukemia & Lymphoma Society of America. WW is supported by the Austrian Science Foundation (J 3578-B21). CGA is supported by Kay Kendall Leukaemia Fund clinical research fellowship. UM is supported by a Cancer Research UK Clinician Scientist Fellowship. Work in the Huntly lab is supported by the European Research Council, the MRC (UK), Bloodwise, the Cambridge NIHR funded BRC, KKLF and a WT/MRC Stem Cell centre grant. Work in the Green and Huntly Labs is supported by core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research (100140/z/12/z) and Wellcome Trust-MRC Cambridge Stem Cell Institute (097922/Z/11/Z)