Analysis of Financial Barriers Experienced by Prospective Genetic Counseling Students.

PURPOSE: High costs of applying to genetic counseling graduate programs (GCGPs) are likely a barrier to workforce diversification. We sought to determine application costs and assess differences between individuals of historically underrepresented racial and ethnic backgrounds in medicine (hURM) and non-hURM applicants. METHODS: Applicants to GCGPs between 2005-2020 were surveyed about application history, related expenses, volunteer hours, and financial resources; 383 responses were analyzed. RESULTS: Median total application costs (MTAC) were $2,634, $4,762, and $5,607 (one, two, and three or more application cycles, respectively). Interview-related items (which includes travel) had the highest median cost (one application cycle: $879). Among those who applied to multiple cycles, hURM respondents had higher MTAC than those of non-hURM ($6,713 versus $4,762, p=0.03) and lower median total volunteer hours (246 versus 381, p=0.03). Parental education level differed by hURM status (p=0.04). Median financial contribution from parents with and without advanced degrees varied significantly (60% vs 2%, p=0.0009). CONCLUSION: Significant costs are incurred during the GCGP application process, but notable differences in costs and resources were observed between hURM and non-hURM applicants. Stakeholders within the profession should implement strategies to reduce financial barriers and the resulting inequities in the application process.

Inter-group violence among early Holocene hunter-gatherers of West Turkana, Kenya.

The nature of inter-group relations among prehistoric hunter-gatherers remains disputed, with arguments in favour and against the existence of warfare before the development of sedentary societies. Here we report on a case of inter-group violence towards a group of hunter-gatherers from Nataruk, west of Lake Turkana, which during the late Pleistocene/early Holocene period extended about 30 km beyond its present-day shore. Ten of the twelve articulated skeletons found at Nataruk show evidence of having died violently at the edge of a lagoon, into which some of the bodies fell. The remains from Nataruk are unique, preserved by the particular conditions of the lagoon with no evidence of deliberate burial. They offer a rare glimpse into the life and death of past foraging people, and evidence that warfare was part of the repertoire of inter-group relations among prehistoric hunter-gatherers.

Impact of Arrhythmia in Hospital Mortality in Acute Ischemic Stroke Patients: A Retrospective Cohort Study in Northern Mexico.

BACKGROUND: Atrial fibrillation has been associated with higher morbidity and mortality rates in acute ischemic stroke patients (AIS). However, there is scarce information regarding the clinical outcomes and strokes' characteristics among AIS patients with other type of arrhythmias. OBJECTIVE: Our study aims to analyze the hospital mortality rate, stroke characteristics, and clinical and demographical data of patients with any post-stroke arrhythmia. METHODS: Retrospective cohort study of AIS patients with 24h-Holter monitoring during hospital admission recruited between 2015-2020, outcomes were measured using the modified Rankin scale. RESULTS: 597 patients (61.13±13.61 years; 352 men) were included. Arrhythmias were diagnosed in 33 (5.5%), with atrial fibrillation as the most common finding (82%). Age was related to a higher rate of arrhythmia (P = 0.014). A larger prevalence of cardioembolic strokes (69.7% vs 16.6%, P < 0.05) and AIS in the middle cerebral artery's vascular territory (78.8% vs 58.7%, P < 0.05) were found amongst patients with an arrhythmia. No significant association was found between NIHSS at admission with neither incidence of arrhythmia nor mortality. Within the arrhythmia group, three in-hospital deaths were reported: one AF, one ventricular arrhythmia and one second-degree atrioventricular block. In a logistic regression analysis, patients with any kind of arrhythmia had a higher mortality rate (9.1% vs 1.2%, P = 0.011; OR 6.766, 95% CI 1.552 - 29.500). CONCLUSION: Arrhythmia detection after an AIS was associated with increased in-hospital mortality. Risk factors related to arrhythmia detection were a higher mean age, cardioembolic strokes and AIS affecting the middle cerebral artery.

Effects of Chlorpyrifos Over Reproductive Traits of Three Sympatric Freshwater Crustaceans.

The exposure to environmentally relevant chlorpyrifos concentrations (0.03, 0.06 and 0.12 µg chlorpyrifos L-1) causes increases in precopulatory guardian behavior time, amplexus reformulation after exposure and in the number of ovigerous females in the amphipod Hyalella curvispina. Effects in incubation period, effective hatching and median lethal concentration on the decapods Macrobrachium borellii and Aegla uruguayana, both in adults and embryos, were achieved at higher concentrations than those found in the environment. Environmentally relevant chlorpyrifos concentrations appear not to affect decapods but several effects in reproductive traits of amphipods were observed.

Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE).

BACKGROUND: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels. PATIENTS AND METHODS: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab [2.8 g intravenously (i.v.) every 2 weeks] or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate. RESULTS: A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%). CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.

Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group.

BACKGROUND: The bevacizumab-Avastin® adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). PATIENTS AND METHODS: Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. RESULTS: A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51-10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07-1.55; P = 0.008] and 1.16 (95% CI 0.99-1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95-1.39; P = 0.147) and 1.1 (95% CI 0.93-1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. CONCLUSIONS: S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. CLINICAL TRIAL IDENTIFICATION: NCT00112918.

Genotype-based selection of treatment of patients with advanced colorectal cancer (SETICC): a pharmacogenetic-based randomized phase II trial.

Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.

Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry.

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.

Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial.

BACKGROUND: Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin αν heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part). METHODS: Eligible patients had KRAS (exon 2) wild-type mCRC and had received prior oxaliplatin-containing therapy. The trial comprised an initial safety run-in using abituzumab doses up to 1000 mg combined with a standard of care (SoC: cetuximab plus irinotecan) and a phase II part in which patients were randomised 1 : 1 : 1 to receive abituzumab 500 mg (arm A) or 1000 mg (arm B) every 2 weeks combined with SoC, or SoC alone (arm C). The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (RR) and tolerability. Associations between tumour integrin expression and outcomes were also assessed. RESULTS: Phase I showed that abituzumab doses up to 1000 mg were well tolerated in combination with SoC. Seventy-three (arm A), 71 (arm B) and 72 (arm C) patients were randomised to the phase II part. Baseline characteristics were balanced. PFS was similar in the three arms: arm A versus SoC, hazard ratio (HR) 1.13 [95% confidence interval (CI) 0.78-1.64]; arm B versus SoC, HR 1.11 (95% CI 0.77-1.61). RRs were also similar. A trend toward improved OS was observed: arm A versus SoC, HR 0.83 (95% CI 0.54-1.28); arm B versus SoC, HR 0.80 (95% CI 0.52-1.25). Grade ≥3 treatment-emergent adverse events were observed in 72%, 78% and 67% of patients. High tumour integrin αvß6 expression was associated with longer OS in arms A [HR 0.55 (0.30-1.00)] and B [HR 0.41 (0.21-0.81)] than in arm C. CONCLUSION: The primary PFS end point was not met, although predefined exploratory biomarker analyses identified subgroups of patients in whom abituzumab may have benefit. The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable. Further study is warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT01008475.

Crescentic glomerulonephritis: data from the Spanish Glomerulonephritis Registry.

BACKGROUND: Crescentic glomerulonephritis (CGN) is a histological finding that implies rapid deterioration of renal function and can be related to different diseases, such as type 1 or anti-glomerular basement membrane antibody (Goodpasture) disease, type 2 or immune complex CGN and type 3 or pauci-immune disease. AIM: The present study describes CGN and its characteristics based on the data from the Spanish Glomerulonephritis Registry. METHODS: An analysis was made of all native renal biopsies obtained from patients during 1994-2013 and classified as CGN. A patient epidemiological and clinical data questionnaire was completed by the 120 centres involved. RESULTS: A total of 21,774 biopsies was performed, of which 2089 (8.1%) corresponded to CGN (211 type 1, 177 type 2 and 1701 type 3). Renal function was poorer in type 1 compared with types 2 and 3, and proteinuria was higher in type 2 compared to types 1 and 3. Patients diagnosed with CGN type 3 were older than those with types 1 and 2, but less hypertensive than the type 2 patients. No differences in the urine test findings were found between types 1 and 2. Microhaematuria was the most frequent feature in general, as well as in type 3 compared with types 1 and 2. The main indication for biopsy was acute renal injury. Age was the only difference between type 1 patients with and without alveolar haemorrhage (53 [33-67] vs 64 [46-73], P = 0.008). CONCLUSION: Although classified as the same entity, the different types of CGN have different features that must be taken into account.

Scanning electron microscopy of superficial defects in Twisted files and Reciproc nickel-titanium files after use in extracted molars.

AIM: To evaluate the usage and superficial defects in size 25, 0.08 taper Twisted files (TF) and R25 Reciproc files after root canal instrumentation. METHODOLOGY: One hundred and twenty mandibular molars with root canal curvature, ranging from 15° to 30° and a 4-5 mm radius, were randomly divided into two groups according to single-file instrumentation: size 25, 0.08 taper TF or R25 files. A total of fifteen files per group were evaluated before and after three, six, nine and 12 uses. The instruments were fixed in custom-made holders and photographed using scanning electron microscopy at ×260 to ×1200 magnifications. The presence of superficial defects (plastic deformation, microcracks, fracture, craters, disruption of the cutting edges and blunt edges) was scored from the pre- and post-usage photographs. Chi-squared test was used to analyse differences after usages in both groups individually. Two-way anova was used to analyse differences between both instruments. The level of significance for all analyses was 5%. RESULTS: Superficial defects were observed after the instrumentation of six root canals in the TF group and after the instrumentation of nine root canals in the R25 group. Plastic deformation and disruption of cutting edges were the prevalent defects observed in the TF group, and craters and blunt edges were observed in R25 files. The presence of defects was significantly increased with successive usages in both groups (P < 0.05), but TF had more superficial defects than R25 files (P < 0.001). Dentine debris was observed on all instruments. No instruments fractured. CONCLUSIONS: Instrumentation was possible for six root canals with TF files and nine root canals with R25 files before the presence of superficial defects appeared. Differences in the prevalence and development of superficial defects were observed between the TF and R25 files.

Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.

BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.

Characterization of dsRed2-positive cells in the doublecortin-dsRed2 transgenic adult rat retina.

Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and young immature neurons of the developing and adult brain, where it is involved in neuronal differentiation, migration and plasticity. Moreover, its expression pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models have been previously used to investigate adult neurogenesis. In this study, we characterize dsRed2 reporter protein-expressing cells in the adult retina of the transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with putative neurogenic activity. Additionally, we confirmed the expression of the dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus. Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA-NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning microscopy. In addition, brain sections of transgenic rats were analyzed for dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex and dentate gyrus. Endogenous DCX expression in the adult retina was confined to horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2 reporter protein. In addition, we encountered dsRed2 expression in various other cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of amacrine cells, a minority of bipolar cells and in perivascular cells. Since also RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to study RGCs in vivo under various conditions. Müller glial cells, which have previously been identified as cells with stem cell features and with neurogenic potential, did express neither endogenous DCX nor the dsRed2 reporter. However, and surprisingly, we identified a perivascular glial cell type expressing the dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing with the neural stem cell marker Sox2. These findings suggest the so far undiscovered existence of perivascular associated cell with neural stem cell-like properties in the adult retina.

Global disease burden of conditions requiring emergency surgery.

BACKGROUND: Surgical disease is inadequately addressed globally, and emergency conditions requiring surgery contribute substantially to the global disease burden. METHODS: This was a review of studies that contributed to define the population-based health burden of emergency surgical conditions (excluding trauma and obstetrics) and the status of available capacity to address this burden. Further data were retrieved from the Global Burden of Disease Study 2010 and the University of Washington's Institute for Health Metrics and Evaluation online data. RESULTS: In the index year of 2010, there were 896,000 deaths, 20 million years of life lost and 25 million disability-adjusted life-years from 11 emergency general surgical conditions reported individually in the Global Burden of Disease Study. The most common cause of death was complicated peptic ulcer disease, followed by aortic aneurysm, bowel obstruction, biliary disease, mesenteric ischaemia, peripheral vascular disease, abscess and soft tissue infections, and appendicitis. The mortality rate was higher in high-income countries (HICs) than in low- and middle-income countries (LMICs) (24.3 versus 10.6 deaths per 100,000 inhabitants respectively), primarily owing to a higher rate of vascular disease in HICs. However, because of the much larger population, 70 per cent of deaths occurred in LMICs. Deaths from vascular disease rose from 15 to 25 per cent of surgical emergency-related deaths in LMICs (from 1990 to 2010). Surgical capacity to address this burden is suboptimal in LMICs, with fewer than one operating theatre per 100,000 inhabitants in many LMICs, whereas some HICs have more than 14 per 100,000 inhabitants. CONCLUSION: The global burden of surgical emergencies is described insufficiently. The bare estimates indicate a tremendous health burden. LMICs carry the majority of emergency conditions; in these countries the pattern of surgical disease is changing and capacity to deal with the problem is inadequate. The data presented in this study will be useful for both the surgical and public health communities to plan a more adequate response.

Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia - open-label trial.

OBJECTIVES: The objective of the study was to test the efficacy, safety and tolerability of triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia (FRDA) patients in a clinical pilot study. PATIENTS AND METHODS: Patients included in this study were 10 males and three females, 14-61 years of age (average 30.2 ± 12.1), diagnosed with FRDA with normal ventricular function. Patients were treated with triple therapy with deferiprone at 5-25 mg/kg/day, idebenone at 10-20 mg/kg/day and riboflavin at 10-15 mg/kg/day for 15-45 months. The efficacy of this triple therapy was assessed by change from baseline on the scale for the assessment and rating of ataxia (SARA) and by the change from baseline in echocardiogram parameters. RESULTS: Four patients discontinued due to adverse events (AEs) related with deferiprone. The annual worsening rate (AWR) was estimated in this series as 0.96 (CI 95%: 0.462-1.608) SARA score, whereas AWR for our FRDA cohort was estimated as 2.05 ± 1.23 SARA score. LVMI only decreased by 6.5 g/m(2) (6.2%) at the end of the first year of therapy. LVEF remained stable, except in case of three patients. CONCLUSION: Our results seem to indicate some uncertain benefit on the neurological and heart functions of this triple therapy in FRDA.

Individual factors and school-based policies related to adherence to physical activity recommendations in Spanish adolescents.

Our objective was to identify individual- and school-level contextual factors related to adherence to the recommendations for physical activity in adolescents. The study used a representative sample of 15,902 students from 328 schools aged 11-18 years participating in the Spanish Health Behaviour in School-aged Children (HBSC) survey 2006. In addition to the student questionnaire, the school management board completed a questionnaire about school-based policies related to physical activity. Adherence to the recommendations was defined as "having carried out moderate and/or vigorous physical activity for at least 60 min a day on five or more days during the last week". Analysis was undertaken using multilevel logistic regression models. Individual factors associated in a statistically significant way with a higher non-compliance were: being female; being older; immigrants; tobacco smoking; being overweight or obese; low consumption of fruit and vegetables; low level of satisfaction with life; not having a high level of academic achievement; and spending a lot of time studying. The family variables were: not undertaking sports activities with the family; low socioeconomic status; and a low level of satisfaction with family relationships. Compared with schools that have a low level of policies to promote physical activities, those with a high level of promotion had an odds ratio of 0.76 (CI 95 %, 0.61-0.94). In summary, irrespective of personal and family factors, students from schools with better policies of promotion of physical activity showed a higher compliance with the recommendations.

Clast shape-fabric analysis: A comprehensive and efficient methodology to measure particle-orientation data in solid and loose volcaniclastic deposits.

Fabric analysis is essential for understanding the evolution of volcaniclastic deposits. Here we present a comprehensive and efficient methodology, called "Clast shape-fabric analysis," which is part of the Quantitative Textural Analysis (QTA). This methodology combines high-resolution image analysis techniques with geospatial data processing tools. The fabric of a deposit refers to the three-dimensional orientation of the particles with respect to space, where the degree of iso-orientation of the major axes of the particles is taken into account. The process begins with the collection of oriented samples in the field. Then, in the laboratory, the samples are processed to obtain high-resolution images. The final stage involves the analysis of these images using the FabricS program, which combines image processing techniques and circular statistics. An application of the method was made at the Joya Honda Maar in Mexico, where shape-fabric analysis was used to identify the emission centers of pyroclastic materials. In summary, the "Clast shape-fabric analysis" is a reliable, low-cost and high-potential methodology that can be applied in several geoscientific disciplines and other areas of scientific research.•New Methodology for shape-fabric analysis is presented.•The methodology involves field work, laboratory work and image analysis.•Identification of particle orientations in volcaniclastic deposits.