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Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear.
To explore the extent and nature of ‘treatment gaps’ (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK.
Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced.
Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment.
There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.
Echinococcus shiquicus is currently limited to the Qinghai–Tibet plateau, a large mountainous region in China. Although the zoonotic potential remains unknown, progress is being made on the distribution and intermediate host range. In this study, we report E. shiquicus within Gansu and Qinghai provinces in regions located not only around the central areas but also the southeast edge of the plateau and describe their genetic relationship with previous isolates from the plateau. From 1879 plateau pikas examined, 2.39% (95% CI 1.79–3.18) were infected with E. shiquicus. The highest prevalence of 10.26% (4.06–23.58) was recorded in Makehe town, Qinghai province. Overall the prevalence was marginally higher in Qinghai (2.5%, CI 1.82–3.43) than in Gansu (2%, CI 1.02–3.89). The cox1 and nad1 genes demonstrated high and low haplotype and nucleotide diversities, respectively. The median-joining network constructed by the cox1–nad1 gene sequences demonstrated a star-like configuration with a median vector (unsampled haplotype) occupying the centre of the network. No peculiar distinction or common haplotype was observed in isolates originating from the different provinces. The presence of E. shiquicus in regions of the southeast and northeast edges of the Qinghai–Tibet plateau and high genetic variation warrants more investigation into the haplotype distribution and genetic polymorphism by exploring more informative DNA regions of the mitochondrial genome to provide epidemiologically useful insight into the population structure of E. shiquicus across the plateau and its axis.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
We followed up a cohort (n = 35) of clients with an “At Risk Mental State” (ARMS) for almost 2 years (mean 21.3 months). At baseline, these clients had taken part in research looking at the relationship between reasoning biases, memory, personality styles and delusional ideation. During the follow-up period, clients underwent a package of intervention from a specialist early detection team. Eighty percent (n = 28) of these clients were successfully re-interviewed. There was improvement across the cohort as a whole, however five participants (17.9%) had made the transition to psychosis at follow-up. Those who had become psychotic had lower levels of manic symptomatology at baseline than those who did not enter the first episode. Further, across the cohort, impaired working memory and delusional ideation at baseline combined to predict 45% of the delusional ideation at follow-up. These preliminary findings suggest that working memory impairments may be linked to the persistence of delusional ideation and that manic symptoms in someone with an ARMS may suggest that such an individual is less likely to develop a frank psychotic episode.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
The diagnosis of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis relies on the detection of NMDAR IgG autoantibodies in the serum or cerebrospinal fluid (CSF) of symptomatic patients. Commercial kits are available that allow NMDAR IgG autoantibodies to be measured in local laboratories. However, the performance of these tests outside of reference laboratories is unknown.
To report an unexpectedly low rate of NMDAR autoantibody detection in serum from patients with anti-NMDAR encephalitis tested using a commercially available diagnostic kit in an exemplar clinical laboratory.
Paired CSF and serum samples from seven patients with definite anti-NMDAR encephalitis were tested for NMDAR IgG autoantibodies using commercially available cell-based assays run according to manufacturer’s recommendations. Rates of autoantibody detection in serum tested at our center were compared with those derived from systematic review and meta-analyses incorporating studies published during or before March 2019.
NMDAR IgG autoantibodies were detected in the CSF of all patients tested at our clinical laboratory but not in paired serum samples. Rates of the detection were lower than those previously reported. A similar association was recognized through meta-analyses, with lower odds of NMDAR IgG autoantibody detection associated with serum testing performed in nonreference laboratories.
Commercial kits may yield lower-than-expected rates of NMDAR IgG autoantibody detection in serum when run in exemplar clinical (nonreference) laboratories. Additional studies are needed to decipher the factors that contribute to lower-than-expected rates of serum positivity. CSF testing is recommended in patients with suspected anti-NMDAR encephalitis.
OBJECTIVES/SPECIFIC AIMS: The aims of this study are 2-fold: (1) to determine if maternal schistosomiasis affects maternal immunity to tetanus and/or transplacental transfer of antitetanus toxoid (TT) immunoglobulin G (IgG) from mother to infant and (2) determine the influence of maternal schistosomiasis on infant BCG vaccine immunogenicity. METHODS/STUDY POPULATION: The study will utilize blood samples from a historic cohort of 100 mother-infant pairs from Kisumu, Kenya, a schistosomiasis-endemic area. For the first aim, we will evaluate maternal schistosomal circulating anodic antigen, which has improved sensitivity and specificity to detect active schistosomiasis from serum, and antisoluble egg antigen IgG positivity compared with quantitative maternal anti-TT IgG at delivery and anti-TT IgG cord blood to maternal blood ratio (cord:maternal ratio). For the second aim, we will evaluate association between maternal schistosomiasis as detected by circulating anodic antigen and antisoluble egg antigen IgG at delivery and infant BCG-specific Th1-cytokine positive CD4+ cells at 10 weeks following BCG vaccination at birth. RESULTS/ANTICIPATED RESULTS: We hypothesize that active maternal schistosomiasis will be associated with decreased maternal anti-TT IgG and reduced efficiency of transplacental transfer, as measured by infant cord blood to maternal blood ratio of anti-TT IgG. We also expect that maternal schistosomiasis will be associated with decreased infant immunogenicity to BCG vaccine. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a formative study on infant vaccine immunity using laboratory methodology not previously applied. Understanding infant immunity in the setting of maternal schistosomiasis will inform vaccination strategies and tailor vaccine development in schistosome-endemic areas such as Kenya, where neither TB nor neonatal tetanus have been eradicated. Additionally, our results will inform public health policies to consider integration of antischistosomal agents in antenatal care.
The volume of food purchased by the American military makes it perhaps the single largest intermediated market for food in the USA. Consequently, it is not surprising that those seeking to enhance the economic viability of small and mid-scale farms may view military bases as a promising market for locally produced foods. This is a challenging prospect, however, due to the centralized structure of military command, the nature of the military procurement system and federal mandates to obtain products that maximize value at the lowest available cost. This paper describes the US military food procurement system and the work of a 3-yr initiative to increase the amount of locally produced, source-identified products used at a North Carolina military installation. Our experiences serve as a cautionary tale, with this paper designed as both a primer on ‘how it works’ for food procurement at the federal and base level, and a description of our largely unsuccessful attempts to increase the volume of local food products from small-/mid-scale producers moving through the supply chain into base dining halls and restaurants. Based on our experiences, we also make recommendations on possible entry points for local food and farm advocates to work within the existing system to localize food procurement.
It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population.
To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis.
We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode.
The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment.
Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes.
The macrophyte swamp stonecrop has invaded a wide range of wetland habitats across Europe. An experiment was conducted within an invaded fen habitat, which tested whether the presence of grazing disturbance affected the relative abundance of swamp stonecrop, and whether any detected effect was suppressive or facilitative. The abundance of swamp stonecrop and co-occurring resident plants was monitored within fenced grazing exclosures and in adjacent unfenced plots. Swamp stonecrop abundance was higher in the unfenced plots compared to the fenced exclosures (t(87) = 28.974, P < 0.001), whereas the abundance of co-occurring plants was higher in the fenced exclosures compared to the unfenced plots (t(87) = 6.264, P < 0.001). These results indicate that the presence of large vertebrates could facilitate a higher abundance of swamp stonecrop in situations where competitive resident plant species were selectively removed by these grazing animals.
The model diatom Thalassiosira pseudonana is believed to be a single species with a global distribution, but it has not been confirmed previously whether isolates from different environmental and geographic origins are genotypically and phenotypically identical. In the present study, a polyphasic approach was employed to characterize nine clonal isolates, plus an additional replicate of one of the isolates, of the diatom T. pseudonana from culture collections to investigate whether there was any cryptic speciation in the publicly available strains of this species. Morphological analysis using scanning electron microscopy concluded that the strains were indistinguishable. Furthermore, conventional DNA barcoding genes (SSU rDNA, ITS1 and ITS2 rDNA and rbcL), revealed no nucleotide variation among the strains tested. On employing a whole genome fingerprinting technique, Amplified Fragment Length Polymorphism (AFLP), three clusters were revealed, although the level of variation between the clusters was surprisingly low. These findings indicate a low level of diversity among these cultured T. pseudonana strains, despite their wide spatial and temporal distribution and the salinity range of their original habitats. Based on the limited number of available strains, this suggests that T. pseudonana is a highly conserved diatom that nevertheless has an ability to tolerate wide ranges of salinity and populate varied geographic locations.
All same-sex dizygotic (DZ) twins and approximately one-third of monozygotic (MZ) twin pairs have separate placentas, making it impossible to use the number of placentas to determine zygosity. Zygosity determination is further complicated because incorrect assumptions are often made, such as that only DZ pairs have two placentas and that all MZ pairs are phenotypically identical. These assumptions, by twins, their families and health professionals, along with the lack of universal zygosity testing for same-sex twins, has led to confusion within the twin community, yet little research has been conducted with twins about their understanding and assumptions about zygosity. We aimed to explore and quantify understanding and assumptions about zygosity using twins attending an Australian twin festival. We recruited 91 twin pairs younger than 18 years of age and their parents, and 30 adult twin pairs who were all uncertain of their zygosity, to complete one pen and paper questionnaire and one online questionnaire about their assumed zygosity, reasons for their assumptions and the importance of accurate zygosity knowledge. Responses were compared with their true zygosity measured using a genetic test. We found a substantial proportion of parents and twins had been misinformed by their own parents or medical professionals, and that knowledge of their true zygosity status provided peace of mind and positive emotional responses. For these reasons we propose universal zygosity testing of same-sex twins as early in life as possible and an increase in education of medical professionals, twins and families of twins about zygosity issues.
The WAIS (West Antarctic Ice Sheet) Divide deep ice core was recently completed to a total depth of 3405 m, ending 50 m above the bed. Investigation of the visual stratigraphy and grain characteristics indicates that the ice column at the drilling location is undisturbed by any large-scale overturning or discontinuity. The climate record developed from this core is therefore likely to be continuous and robust. Measured grain-growth rates, recrystallization characteristics, and grain-size response at climate transitions fit within current understanding. Significant impurity control on grain size is indicated from correlation analysis between impurity loading and grain size. Bubble-number densities and bubble sizes and shapes are presented through the full extent of the bubbly ice. Where bubble elongation is observed, the direction of elongation is preferentially parallel to the trace of the basal (0001) plane. Preferred crystallographic orientation of grains is present in the shallowest samples measured, and increases with depth, progressing to a vertical-girdle pattern that tightens to a vertical single-maximum fabric. This single-maximum fabric switches into multiple maxima as the grain size increases rapidly in the deepest, warmest ice. A strong dependence of the fabric on the impurity-mediated grain size is apparent in the deepest samples.
When an environmental accident such as an oil spill occurs, several things happen. There can be immediate efforts to contain the damage to natural ecosystems or human structures or livelihoods. Steps can be taken to provide relief to the people or environments most immediately affected. If the accident is sufficiently large, media accounts can fuel responses by the broader public. For damages resulting from human-caused accidents, claims and counter-claims of the magnitude and extent of the accident and its consequences will be made and then amplified, often followed (in the United States, at least) by litigation. All of these consequences require knowledge of what really happened – where did the oil go, what natural resources or services were affected, and how persistent were these effects? As the chapters in this book amply demonstrate, the need for careful, rigorous, and objective science is paramount.
Just because there is a need for careful, rigorous, and objective science, however, does not mean that it is easily attainable. Because of demands for immediate action and the heightened emotions following an environmental accident, attempts to document the ecological effects and subsequent recovery run the risk of being hastily developed and inadequately designed. This can foster never-ending arguments about conclusions. Such accidents occur against a complex and dynamically varying environmental background, so they cannot be treated as traditional experiments to be analyzed with straightforward statistical procedures that are planned in advance. There is only a single replicate of the “treatment” (i.e., the accident), there are no pre-established controls, and a welter of other factors with varying degrees of intercorrelation confounds attempts to attribute observed changes to the environmental accident. After all, the real world is messy! Designing field studies and analyses that are quantitative, objective, and scientifically rigorous under such circumstances is difficult – yet it is essential.
Marine birds are among the most conspicuous elements of coastal ecosystems. Their variety, abundance, visibility, and behavior resonate with the public. They are also particularly vulnerable to oil spills. Most marine-bird species forage at or beneath the water’s surface, where they are at risk of exposure to floating oil. Additionally, many feed and nest along shorelines where floating oil can accumulate, and some form large breeding colonies that are susceptible to oil spills. Over 200 000 marine birds died as a direct consequence of the Exxon Valdez oil spill, and images of oiled birds dominated media coverage. Federal regulations requiring documentation of injuries to natural resources from oil spills (see Chapter 1) prompted multiple studies of marine birds, fueling debates about short- and long-term effects of the spill and subsequent recovery.
Determining how an oil spill (or any large environmental disturbance) affects marine birds is complicated by variation in the environment and in how birds respond to that environment. Coastal environments vary substantially from place to place and time to time. At high-latitude locations such as Prince William Sound (PWS), diurnal and monthly changes in tides; seasonal variations in storms, water temperatures, and productivity; and multiyear changes in ocean temperature and circulation such as El Niño events and the Pacific Decadal Oscillation can have dramatic effects. At any time, marine birds may be responding to a host of environmental factors over a range of scales, from the availability of suitable nesting sites along a small stretch of shoreline to the abundance of prey over a broad region or to variation in hemispheric-scale forces affecting the ocean. Because these influences do not disappear when an oil spill occurs, they and any associated environmental variations must be accounted for when assessing spill effects. Population changes attributed to an oil spill must be rigorously tested and documented, not just inferred.