There is great interest in finding materials possessing quasiparticles with topological properties. Such materials may have novel excitations that exist on their boundaries which are protected ...against disorder. We report experimental evidence that magnons in an insulating kagome ferromagnet can have a topological band structure. Our neutron scattering measurements further reveal that one of the bands is flat due to the unique geometry of the kagome lattice. Spin wave calculations show that the measured band structure follows from a simple Heisenberg Hamiltonian with a Dzyaloshinkii-Moriya interaction. This serves as the first realization of an effectively two-dimensional topological magnon insulator--a new class of magnetic material that should display both a magnon Hall effect and protected chiral edge modes.
International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers.
To describe ...typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel.
Descriptive, using GeoSentinel records.
53 tropical or travel disease units in 24 countries.
42 173 ill returned travelers seen between 2007 and 2011.
Frequencies of demographic characteristics, regions visited, and illnesses reported.
Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported.
Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness.
Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel.
Centers for Disease Control and Prevention.
Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study ...provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality.
One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors.
Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03-0.39) with similar patterns for mortality among technologists born before 1930.
Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.
Abstract The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During ...2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric non-cardia cancer, 123 Oesophageal Squamous Cell Carcinoma (ESCC) and 305 Oesophageal Adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of ⩾1 cup/day was 0.37 (95% CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95% CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last 3 years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95% CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods.
Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of ...seroconversion is unknown.
We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4years (IQR=6–11years, range=0–40years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay).
HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1–155.4) in whites and 17.2-fold (95% CI 1.7–170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30years (N=24), 20–30years (N=148), 10–20years (N=228), and <10years (N=301 cases) (p-trend<0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25years before diagnosis.
The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.
Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological ...mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS).
A total of 118 patients with RMS were randomly ...assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate.
Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p < 0.0001) for 7 and 14 mg, respectively, compared with IFNβ alone at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% p = 0.4355 and 57.9% p = 0.1005 for 7 and 14 mg, respectively).
Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone.
This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.
This multi-centre prospective cohort study aimed to investigate non-inferiority in patients’ overall survival when treating potentially resectable colorectal cancer liver metastasis (CRLM) with ...stereotactic microwave ablation (SMWA) as opposed to hepatic resection (HR).
Patients with no more than 5 CRLM no larger than 30 mm, deemed eligible for both SMWA and hepatic resection at the local multidisciplinary team meetings, were deliberately treated with SMWA (study group). The contemporary control group consisted of patients with no more than 5 CRLM, none larger than 30 mm, treated with HR, extracted from a prospectively maintained nationwide Swedish database. After propensity-score matching, 3-year overall survival (OS) was compared as the primary outcome using Kaplan-Meier and Cox regression analyses.
All patients in the study group (n = 98) were matched to 158 patients from the control group (mean standardised difference in baseline covariates = 0.077). OS rates at 3 years were 78% (Confidence interval CI 68–85%) after SMWA versus 76% (CI 69–82%) after HR (stratified Log-rank test p = 0.861). Estimated 5-year OS rates were 56% (CI 45–66%) versus 58% (CI 50–66%). The adjusted hazard ratio for treatment type was 1.020 (CI 0.689–1.510). Overall and major complications were lower after SMWA (percentage decrease 67% and 80%, p < 0.01). Hepatic retreatments were more frequent after SMWA (percentage increase 78%, p < 0.01).
SMWA is a valid curative-intent treatment alternative to surgical resection for small resectable CRLM. It represents an attractive option in terms of treatment-related morbidity with potentially wider options regarding hepatic retreatments over the future course of disease.
•Similar 3-year overall survival with thermal ablation versus hepatic resection.•Treatment-related morbidity lower while options for retreatment higher.•Thermal ablation valid treatment for resectable colorectal cancer liver metastases.
Summary Objective The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and ...subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. Design The fourth metacarpal was obtained from 12 human cadaveric donors and baseline μCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. Results Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content ( R2 = 0.86) and equilibrium modulus ( R2 = 0.84), while correlations using Ioxaglate were insignificant ( R2 ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density ( R2 = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R2 = 0.67), trabecular number (Tb.N, R2 = 0.60), and trabecular thickness ( R2 = 0.42), and negative relationships with structural model index (SMI, R2 = 0.78) and trabecular spacing (Tb.Sp, R2 = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV ( R2 = 0.50), Tb.N ( R2 = 0.59) and negatively with Tb.Sp ( R2 = 0.55) and SMI ( R2 = 0.60). Conclusion This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.
We report the results of a search for neutrinoless double-beta decay in a 9.8 kg yr exposure of Te-130 using a bolometric detector array, CUORE-0. The characteristic detector energy resolution and ...background level in the region of interest are 5.1 +/- 0.3 keV FWHM and 0.058 +/- 0.004(stat) +/- 0.002(syst)counts/(keV kg yr), respectively. The median 90% C.L. lower-limit half-life sensitivity of the experiment is 2.9 x 10(24) yr and surpasses the sensitivity of previous searches. We find no evidence for neutrinoless double-beta decay of Te-130 and place a Bayesian lower bound on the decay half-life, T-1/2(0 nu) > 2.7 x 10(24) yr at 90% C.L. Combining CUORE-0 data with the 19.75 kg yr exposure of Te-130 from the Cuoricino experiment we obtain T-1/2(0 nu) > 4.0 x 10(24) yr at 90% C.L. (Bayesian), the most stringent limit to date on this half-life. Using a range of nuclear matrix element estimates we interpret this as a limit on the effective Majorana neutrino mass, m beta beta < 270-760 meV.
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