To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Background: Although previous research has suggested that patients with incidentally discovered low-grade gliomas (iLGG) who undergo surgery prior to the appearance of symptoms have improved outcomes compared to those who are symptomatic, an ideal approach to managing iLGG is not well-established. The purpose of this systematic review is to identify all cases of iLGG in the literature and characterize the effect of the timing of surgery on survival. Methods: We searched EMBASE, MEDLINE, and PubMed for articles related to iLGG. After duplicates were removed, the articles were then screened based on strict inclusion and exclusion criteria. Results: We retrieved 24/1377 unique articles with a total of 175 patients who underwent surgery for iLGG prior to symptoms appearing. The average age was 29.1yrs (range 1-62) and the mean follow-up period was 56 months (range 1-234months). Unfortunately, only 6/24 articles reported progression-free survival (average 32.4months) and only 1/24 reported 10-year survival. Conclusions: The articles we identified favored an early intervention for iLGG, however, there was a considerable lack of long-term follow-up and survival data to justify such a claim. Further studies need to be performed with adequate follow-up data in order to determine the optimal timing of surgical intervention for these patients.
Synthetic biology has a huge potential to produce the next generation of advanced materials by accessing previously unreachable (bio)chemical space. In this prospective review, we take a snapshot of current activity in this rapidly developing area, focusing on prominent examples for high-performance applications such as those required for protective materials and the aerospace sector. The continued growth of this emerging field will be facilitated by the convergence of expertise from a range of diverse disciplines, including molecular biology, polymer chemistry, materials science, and process engineering. This review highlights the most significant recent advances and addresses the cross-disciplinary challenges currently being faced.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
To assess community mental health in suburban Dublin in 2018, 5 years after Ireland’s economic recession ended.
A cross-sectional, face-to-face, household survey was conducted in a random cluster sample of 351 households in Tallaght, a deprived suburb of Dublin.
A majority of respondents (61.3%) reported stress over the previous 12 months, with a higher rate in areas of high (66.9%) compared to lower deprivation (55.5%). Deprivation was not related to rates of loneliness (20.2%), feeling depressed (20.2%), loss of interest (19.7%) or anxiety (22.5%). Mean score for positive mental health (59.3/100, with a higher score indicating better mental health) was lower than that reported in a national sample in 2007 (68/100); positive mental health was associated with not living with a person with chronic illness, self-identifying as ‘non-Irish’ and greater age. Mean score for psychological distress (76.7/100, with a higher score indicating less distress) was also lower than that in 2007 (82/100); less psychological distress was associated with not living with a person with chronic illness or disability, greater age and identifying as non-Irish. The rate of ‘probable mental illness’ over the previous 4 weeks (13.1%) was higher than in 2007 (7%).
Our findings emphasise the high prevalence of stress, especially in deprived suburban areas; the centrality of carer burden in determining mental wellbeing; and associations between positive mental health on the one hand and greater age and identifying as non-Irish on the other.
Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.
We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.
Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.
Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.
There is renewed interest in the inverse association between psychiatric hospital and prison places, with reciprocal time trends shown in more than one country. We hypothesised that the numbers of admissions to psychiatric hospitals and committals to prisons in Ireland would also correlate inversely over time (i.e. dynamic measures of admission and committal rather than static, cross-sectional numbers of places).
Publicly available activity statistics for psychiatric hospitals and prisons in Ireland were collated from 1986 to 2010.
There was a reciprocal association between psychiatric admissions and prison committals (Pearson r=−0.788, p<0.001), an increase of 91 prison committals for every 100 psychiatric hospital admissions foregone.
Penrose’s hypothesis applies to admissions to psychiatric hospitals and prisons in Ireland over time (dynamic measures), just as it does to the numbers of places in psychiatric hospitals and prisons in Ireland and elsewhere (static, cross-sectional measures). Although no causal connection can be definitively established yet, mentally disordered prisoners are usually known to community mental health services. Psychiatric services for prisons and the community should be linked to ensure that the needs of those currently accessing care through prisons can also be met in the community.
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman’s rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.
High unemployment is a hallmark of psychotic illness. Individual placement and support (IPS) may be effective at assisting the vocational recoveries of young people with first-episode psychosis (FEP).
To examine the effectiveness of IPS at assisting young people with FEP to gain employment (Australian and Clinical Trials Registry ACTRN12608000094370).
Young people with FEP (n = 146) who were interested in vocational recovery were randomised using computer-generated random permuted blocks on a 1:1 ratio to: (a) 6 months of IPS in addition to treatment as usual (TAU) or (b) TAU alone. Assessments were conducted at baseline, 6 months (end of intervention), 12 months and 18 months post-baseline by research assistants who were masked to the treatment allocations.
At the end of the intervention the IPS group had a significantly higher rate of having been employed (71.2%) than the TAU group (48.0%), odds ratio 3.40 (95% CI 1.17–9.91, z = 2.25, P = 0.025). However, this difference was not seen at 12- and 18-month follow-up points. There was no difference at any time point on educational outcomes.
This is the largest trial to our knowledge on the effectiveness of IPS in FEP. The IPS group achieved a very high employment rate during the 6 months of the intervention. However, the advantage of IPS was not maintained in the long term. This seems to be related more to an unusually high rate of employment being achieved in the control group rather than a gross reduction in employment among the IPS group.
This paper concentrates on livestock production systems by introducing sustainable housing characteristics, and the type of information required to make an informed choice on environmentally sound materials and systems. It then compares energy use in two contrasting beef cattle systems, one a conventional straw-bedded court and roofed silo, with feed delivered by a side-delivery wagon, and the other a roofless woodchip corral and earth-bank silo, with feed delivered by fore-end loader. The woodchip corral system requires 70% less energy than the conventional bedded court, when the total energy inputs are analysed for preparation of the building materials, construction of the livestock accommodation with associated feed and waste storage, and manufacture and operation of machinery. However, when energy used in feed production is included this dominates the energy budget, accounting for 60% of all energy used in the conventional bedded court, and 85% of energy used in the woodchip corral system.
There is concern that the substantial increases in production in dairy herds that can be achieved will bring greater health and fertility problems. Despite considerable advancements in the understanding of the biology of reproduction and its control, fertility apparently continues to decline. As many factors, including health and nutrition, influence reproductive performance it is generally agreed that a multidisciplinary approach is necessary if improvement in fertility is to be achieved Herd health schemes have evolved to improve health, fertility, productivity and profitability but the uptake of such schemes in the UK has been low. The veterinary input to many farms is at best routine fertility visits, confined to examination of the reproductive tract, and at worst occasional emergency calls. The Dairy Herd Health and Productivity Service (DHHPS) provides the opportunity for veterinary surgeons to lead a multidisciplinary team which can monitor health, fertility and production and can plan, when necessary, remedial action. Over a period of twenty years it has continued to identify infertility, mastitis and lameness as the main reasons for the involuntary disposal of dairy cows, although on some farms BSE has been a major factor. The trend in the last few years has been for an increase in culling for reasons of disease rather than for age or yield. The average disease rates have remained high with over 100 treatments per 100 cows each year for conditions which may directly or indirectly influence reproduction. Blood profiling and condition scoring demonstrated that at least a third of the cows sampled were mobilising excessive fat during transition from the dry period to early lactation. Improving both health and nutrition, before and after calving, would greatly improve reproductive performance in many herds. A team approach, with farmers, veterinarians, nutritionists and other advisors working together with well defined goals and objectives, is necessary if progress is to be made in improving reproductive performance. High yield can not always be the excuse for poor fertility.
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.
The acanthocephalan fauna of Australian freshwater fishes was documented from field surveys, a literature survey and examination of specimens registered in Australian museums. From the 4030 fishes, representing 78 of the 354 Australian freshwater fish species (22%), examined for infection seven species of acanthocephalan were recovered. These species comprised five endemic species, three in endemic genera, two species in cosmopolitan genera, one species not fully identified and 1 putative exotic species recovered from eight species of fish. Of these Edmonsacanthus blairi from Melanotaenia splendida, was the only acanthocephalan found at a relatively high prevalence of 38·6%. These findings are indicative of a highly endemic and possibly depauperate acanthocephalan fauna. Species richness was higher in the tropical regions than the temperate regions of the country. Exotic acanthocephalan species have either not been introduced with their exotic hosts or have been unable to establish their life cycles in Australian conditions. Consequently, acanthocephalans have not yet invaded endemic Australian fish hosts.
To establish if the relatively low rate of involuntary psychiatric admission in a suburban area between 2007 and 2011 was maintained in 2014/2015, and explore key correlates of involuntary status.
We used existing hospital records and data sources to extract rates and selected potential correlates of voluntary and involuntary admission in south west Dublin (catchment area: 273 419 people) over 18 months in 2014/2015 and compared these with published national data from the census and Health Research Board.
The rate of involuntary admission in the suburban area studied between 2007 and 2011 was 33.8 involuntary admissions per 100 000 population annually, which was lower than the national rate (48.6). By 2014/2015, the rate of involuntary admission in this area had risen to 46.8 involuntary admissions per 100 000 population annually, similar to the national rate (44.9). Nevertheless, the overall (voluntary and involuntary) admission rate in the suburban area (346.7 admissions per 100 000 population annually) was still lower the national rate (387.9), owing to a lower rate of voluntary admission in the suburban area (299.9) compared to Ireland as a whole (342.9). Multi-variable testing demonstrated that diagnosis was the strongest driver of involuntary admission in the suburban area: this area had 28.5 involuntary admissions per 100 000 population annually with schizophrenia or related disorders, compared to 18.9 nationally. Schizophrenia and related disorders accounted for 60.9% of involuntary admissions in the suburban area compared to 42.1% nationally.
Schizophrenia is the strongest driver of involuntary admission in the suburban area in this study.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Camera trap surveys are a non-invasive way to monitor wildlife populations. Although most often used to study medium- and large-sized mammals, camera traps also detect non-target species. These detections provide useful ecological information on little-known species, but such data usually remain unanalysed. We used detections from camera-trapping surveys of native carnivores and small mammals to examine distribution patterns and occupancy trends of little-known ground-dwelling rainforest birds at seven sites across the Masoala-Makira protected area complex in north-eastern Madagascar. We obtained 4,083 detections of 28 bird species over 18,056 trap nights from 200 to 2013. We estimated occupancy across the Masoala-Makira protected area complex (hereafter, landscape occupancy) and annual trends in occupancy at three resurveyed sites for five commonly observed species. Landscape occupancy across Masoala-Makira ranged from 0.75 (SE 0.09; Madagascar Magpie-robin Copsychus albospecularis) to 0.25 (SE 0.06; Scaly Ground-roller Geobiastes squamiger). Ground-dwelling forest bird occupancy was similar at forest sites that ranged from intact to fully degraded; however, three species were detected less often at sites with high feral cat trap success. Nearly half of all focal species showed declines in annual occupancy probability at one resurveyed site (S02) from 2008 to 2013. The declines in ground-dwelling bird occupancy could have community-wide consequences as birds provide ecosystem services such as seed dispersal and pest regulation. We suggest immediate conservation measures—such as feral cat removal—be implemented to protect ground-dwelling forest birds and other threatened taxa across this landscape.
This article outlines a new method for surveys to study elections and voter attitudes. Pre-election surveys often suffer from an inability to identify and survey the likely electorate for the upcoming election. We propose a new and inexpensive method to conduct representative surveys of the electorate. We demonstrate the performance of our method in producing a representative sample of the future electorate that can be used to study campaign dynamics and many other issues. We compare pre-election outcome forecasts to election outcomes in seven primary and general election surveys conducted prior to the 2008 and 2010 primary and general elections in three states. The results indicate that the methodology produces representative samples, including in low-turnout elections such as primaries where traditional methods have difficulty consistently sampling the electorate. This new methodology combines Probability Proportional to Size (PPS) sampling, mailed invitation letters, and online administration of the questionnaire. The PPS sample is drawn based on a model employing variables from the publicly available voter file to produce a probability of voting score for each individual voter. The proposed method provides researchers a valuable tool to study the attitudes of the voting public.