We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save 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 saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
The consent process for research studies can be burdensome for potential participants due to complex information and lengthy consent forms. This pragmatic study aimed to improve the consent experience and evaluate its impact on participant decision making, study knowledge, and satisfaction with the In Our DNA SC program, a population-based genomic screening initiative. We compared two consent procedures: standard consent (SC) involving a PDF document and enhanced consent (EC) incorporating a pictograph and true or false questions. Decision-making control, study knowledge, satisfaction, and time to consent were assessed. We analyzed data for 109 individuals who completed the SC and 96 who completed the EC. Results indicated strong decision-making control and high levels of knowledge and satisfaction in both groups. While no significant differences were found between the two groups, the EC experience took longer for participants to complete. Future modifications include incorporating video modules and launching a Spanish version of the consent experience. Overall, this study contributes to the growing literature on consent improvements and highlights the need to assess salient components and explore participant preferences for receiving consent information.
To determine how engagement of the hospital and/or vendor with performance improvement strategies combined with an automated hand hygiene monitoring system (AHHMS) influence hand hygiene (HH) performance rates.
The study was conducted in 58 adult and pediatric inpatient units located in 10 hospitals.
Methods:
HH performance rates were estimated using an AHHMS. Rates were expressed as the number of soap and alcohol-based hand rub portions dispensed divided by the number of room entries and exits. Each hospital self-assigned to one of the following intervention groups: AHHMS alone (control group), AHHMS plus clinician-based vendor support (vendor-only group), AHHMS plus hospital-led unit-based initiatives (hospital-only group), or AHHMS plus clinician-based vendor support and hospital-led unit-based initiatives (vendor-plus-hospital group). Each hospital unit produced 1–2 months of baseline HH performance data immediately after AHHMS installation before implementing initiatives.
Results:
Hospital units in the vendor-plus-hospital group had a statistically significant increase of at least 46% in HH performance compared with units in the other 3 groups (P ≤ .006). Units in the hospital only group achieved a 1.3% increase in HH performance compared with units that had AHHMS alone (P = .950). Units with AHHMS plus other initiatives each had a larger change in HH performance rates over their baseline than those in the AHHMS-alone group (P < 0.001).
Conclusions:
AHHMS combined with clinician-based vendor support and hospital-led unit-based initiatives resulted in the greatest improvements in HH performance. These results illustrate the value of a collaborative partnership between the hospital and the AHHMS vendor.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Racial identification is a critical factor in understanding a multitude of important outcomes in many fields. However, inferring an individual’s race from ecological data is prone to bias and error. This process was only recently improved via Bayesian improved surname geocoding (BISG). With surname and geographic-based demographic data, it is possible to more accurately estimate individual racial identification than ever before. However, the level of geography used in this process varies widely. Whereas some existing work makes use of geocoding to place individuals in precise census blocks, a substantial portion either skips geocoding altogether or relies on estimation using surname or county-level analyses. Presently, the trade-offs of such variation are unknown. In this letter, we quantify those trade-offs through a validation of BISG on Georgia’s voter file using both geocoded and nongeocoded processes and introduce a new level of geography—ZIP codes—to this method. We find that when estimating the racial identification of White and Black voters, nongeocoded ZIP code-based estimates are acceptable alternatives. However, census blocks provide the most accurate estimations when imputing racial identification for Asian and Hispanic voters. Our results document the most efficient means to sequentially conduct BISG analysis to maximize racial identification estimation while simultaneously minimizing data missingness and bias.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Comprising Holostei and Teleostei, the ~32,000 species of neopterygian fishes are anatomically disparate and represent the dominant group of aquatic vertebrates today. However, the pattern by which teleosts rose to represent almost all of this diversity, while their holostean sister-group dwindled to eight extant species and two broad morphologies, is poorly constrained. A geometric morphometric approach was taken to generate a morphospace from more than 400 fossil taxa, representing almost all articulated neopterygian taxa known from the first 150 million years—roughly 60%—of their history (Triassic‒Early Cretaceous). Patterns of morphospace occupancy and disparity are examined to: (1) assess evidence for a phenotypically “dominant” holostean phase; (2) evaluate whether expansions in teleost phenotypic variety are predominantly abrupt or gradual, including assessment of whether early apomorphy-defined teleosts are as morphologically conservative as typically assumed; and (3) compare diversification in crown and stem teleosts. The systematic affinities of dapediiforms and pycnodontiforms, two extinct neopterygian clades of uncertain phylogenetic placement, significantly impact patterns of morphological diversification. For instance, alternative placements dictate whether or not holosteans possessed statistically higher disparity than teleosts in the Late Triassic and Jurassic. Despite this ambiguity, all scenarios agree that holosteans do not exhibit a decline in disparity during the Early Triassic‒Early Cretaceous interval, but instead maintain their Toarcian‒Callovian variety until the end of the Early Cretaceous without substantial further expansions. After a conservative Induan‒Carnian phase, teleosts colonize (and persistently occupy) novel regions of morphospace in a predominantly gradual manner until the Hauterivian, after which expansions are rare. Furthermore, apomorphy-defined teleosts possess greater phenotypic variety than typically assumed. Comparison of crown and stem teleost partial disparity indicates that, despite a statistically significant increase in crown teleost disparity between the Late Jurassic and earliest Cretaceous, stem teleosts remained important long-term contributors to overall teleost disparity during this time.
The rate at which the poaching of rhinoceroses has escalated since 2010 poses a threat to the long-term persistence of extant rhinoceros populations. The policy response has primarily called for increased investment in military-style enforcement strategies largely based upon simple economic models of rational crime. However, effective solutions will probably require a context-specific, stakeholder-driven mix of top-down and bottom-up mechanisms grounded in theory that represents human behaviour more realistically. Using a problem-oriented approach we illustrate in theory and practice how community-based strategies that explicitly incorporate local values and institutions are a foundation for combating rhinoceros poaching effectively in specific contexts. A case study from Namibia demonstrates how coupling a locally devised rhinoceros monitoring regime with joint-venture tourism partnerships as a legitimate land use can reconcile individual values represented within a diverse stakeholder group and manifests as both formal and informal community enforcement. We suggest a social learning approach as a means by which international, national and regional governance can recognize and promote solutions that may help empower local communities to implement rhinoceros management strategies that align individual values with the long-term health of rhinoceros populations.
To define the pathology in cases of non-Alzheimer primary degenerative dementia (non-AD PDD), we have studied autopsies from four medical centres accessioned in consecutive years since 1976. Neurochemical studies of the basal forebrain-cortical (BF-C) cholinergic system have been conducted in cases from which frozen tissue was available. Twenty-two cases (mean age 70 years, range 47-86) in which the history was consistent with PDD, but which did not meet anatomic criteria for AD, were selected. Approximately 70 cases of PDD, which were accessioned in the same years and met the anatomic criteria for AD, were excluded. The pathologic findings permitted a classification into six groups: Lewy body disease (LBD), 4 cases; Pick's disease, 6 cases; cortical degeneration with motor neuron disease (CDmnd), 2 cases; hippocampal and temporal lobe sclerosis, 3 cases; few or nonspecific abnormalities, 5 cases; other disorders, 2 cases. Our findings suggest that LBD and Pick's disease account for a large proportion of cases of non-AD PDD in the presenile age group, but that a large number of other disorders occasionally present as PDD. Careful examination of the motor systems, as well as cerebral structures relate' to cognitive function, is important in the neuropathologic evaluation. Lesions of the BF-C cholinergic system have been most consistent and severe in LBD, and have not been identified in CDmnd.