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Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
The photometric phase curves of Saturn's A and B rings exhibit a sharp peak in reflectance when the phase angle approaches zero, commonly known as the opposition effect. Recent work has suggested that the width and amplitude of the opposition effect may be consistent with coherent backscattering from wavelength-sized grains which cover the surfaces of macroscopic ring particles.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Background: Epileptic encephalopathy (EE) is a severe condition in which epileptic activity itself may contribute to severe cognitive and behavioural impairments above and beyond what might be expected from the underlying pathology alone. Next generation sequencing technologies such as whole exome sequencing (WES) can detect underlying genetic causes of in EE. Methods: This report describes genotype-phenotype correlation of 29 subjects with unexplained epileptic encephalopathy, in whom WES, targeting a list of 557 epilepsy-associated genes was performed. Epilepsy phenotyping was done according to current ILAE recommendations. Results: Median age at seizure onset was 14 months (range 1-48). Electroclinical syndromes were applicable for 16/29, 8/16 had a definite/likely diagnosis. 6/8 subjects with West syndrome had variants in ALG13, STXBP1, PAFAH1B1, SLC35A2, CDKL5 and ADSL. 2 patients with Dravet syndrome had variants in SCN1A and PCDH19 respectively. 4/29 had unspecified EE and definite/likely diagnosis due to STXBP1, POLG, and KCNQ2 (2) variants. 4/29 had a possible diagnosis involving GABRB3, ARHGEF9, PCDH19 and SCN3A variants. Conclusions: The high diagnostic yield (definite/likely diagnosis in 11/29 = 38%), involving a broad variety of epilepsy-associated genes in different electroclinical syndromes justifies the diagnostic approach of early onset EE by next generation sequencing.
We describe bright microwave events that were first detected with the Parkes 64-m telescope at 8.4 or 22 GHz from six active-chromosphere stars. In some flares spectral data were obtained over a large frequency range from simultaneous measurements with the Parkes reflector (8.4 or 22 GHz), the Tidbinbilla interferometer (8.4 and 2.29 GHz), the Fleurs synthesis telescope (1.42 GHz) and the Molonglo Observatory synthesis telescope (0.843 GHz). Data on circular polarization were obtained from the Parkes observations at 8.4 GHz.
The stars were in a wide variety of evolutionary states, ranging from a single pre-main-sequence star (HD 36705), two RS CVn binaries (HD 127535, HD 128171), an Algol (HD 132742) and two apparently single K giants (HD 32918 and HD 196818). Their high brightness temperatures, positive spectral indices and low polarization are consistent with optically thick gyrosynchrotron emission from mildly relativistic electrons with average energies 0.5 to 3 MeV gyrating in inhomogeneous magnetic fields of 5 to 100 G.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
We present the first massive frequency analysis of the 1200 first overtone RR Lyrae stars in the Large Magellanic Cloud observed in the first 4.3 yr of the MACHO project. Besides the many new double-mode variables, we also discovered stars with closely spaced frequencies. These variables are most probably nonradial pulsators.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples.
We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537).
Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples.
A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses.
Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24–37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder.
Additive genetic (a2 = 0.48–0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a2 = 0.39) and shared environmental (c2 = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38–0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40–73% of the genetic variance per substance.
Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
We used the winter of 2009–2010, which had minimal influenza circulation due to the earlier 2009 influenza A(H1N1) pandemic, to test the accuracy of ecological trend methods used to estimate influenza-related deaths and hospitalizations. We aggregated weekly counts of person-time, all-cause deaths, and hospitalizations for pneumonia/influenza and respiratory/circulatory conditions from seven healthcare systems. We predicted the incidence of the outcomes during the winter of 2009–2010 using three different methods: a cyclic (Serfling) regression model, a cyclic regression model with viral circulation data (virological regression), and an autoregressive, integrated moving average model with viral circulation data (ARIMAX). We compared predicted non-influenza incidence with actual winter incidence. All three models generally displayed high accuracy, with prediction errors for death ranging from −5% to −2%. For hospitalizations, errors ranged from −10% to −2% for pneumonia/influenza and from −3% to 0% for respiratory/circulatory. The Serfling and virological models consistently outperformed the ARIMAX model. The three methods tested could predict incidence of non-influenza deaths and hospitalizations during a winter with negligible influenza circulation. However, meaningful mis-estimation of the burden of influenza can still result with outcomes for which the contribution of influenza is low, such as all-cause mortality.
We present the KMOS (K-band Multi-Object Spectrograph) Cluster and VIRIAL (VLT IRIFU Absorption Line) Guaranteed Time Observation (GTO) programs. KMOS provides 24 arms each feeding an integral field unit (14×14 spaxels of 0.2″ pixels) for IZ, YJ, H and K band near infrared (NIR) medium resolution spectroscopy (R ∼ 3500). Targets are selected from a 7.2′ diameter patrol field. Ultra-deep spectroscopy of ∼ 80 early-type cluster galaxies (∼ 20hr on source) and ∼ 200 (∼ 10hr on source) early-type field galaxies at 1 < z < 2 will dramatically improve the situation at z > 1 for which measurements of stellar velocity dispersions and absorption indices are limited to a few, often relatively young passively evolving galaxies (e.g. Bezanson 2013). In ESO Periods P92 and P93, 15 nights worth of data has been collected for KMOS-Clusters and 6 nights for VIRIAL: this will be supplemented with more data in upcoming semesters. All galaxies have multiband HST imaging including existing or upcoming WFC3 IR imaging, providing stellar mass maps and sizes. Combined with our dispersion measurements, this will allow us to examine the fundamental plane and the dynamical mass of a large sample of z > 1 galaxies for the first time, for both cluster and field galaxies.