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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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Cross-national studies have found, unexpectedly, that mental disorder prevalence is higher in high-income relative to low-income countries, but few rigorous studies have been conducted in very low-income countries. This study assessed mental disorders in Nepal, employing unique methodological features designed to maximize disorder detection and reporting.
In 2016–2018, 10714 respondents aged 15–59 were interviewed as part of an ongoing panel study, with a response rate of 93%. The World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI 3.0) measured lifetime and 12-month prevalence of selected anxiety, mood, alcohol use, and impulse control disorders. Lifetime recall was enhanced using a life history calendar.
Lifetime prevalence ranged from 0.3% (95% CI 0.2–0.4) for bipolar disorder to 15.1% (95% CI 14.4–15.7) for major depressive disorder. The 12-month prevalences were low, ranging from 0.2% for panic disorder (95% CI 0.1–0.3) and bipolar disorder (95% CI 0.1–0.2) to 2.7% for depression (95% CI 2.4–3.0). Lifetime disorders were higher among those with less education and in the low-caste ethnic group. Gender differences were pronounced.
Although cultural effects on reporting cannot be ruled out, these low 12-month prevalences are consistent with reduced prevalence of mental disorders in other low-income countries. Identification of sociocultural factors that mediate the lower prevalence of mental disorders in low-income, non-Westernized settings may have implications for understanding disorder etiology and for clinical or policy interventions aimed at facilitating resilience.
Retrospective reports of lifetime experience with mental disorders greatly underestimate the actual experiences of disorder because recall error biases reporting of earlier life symptoms downward. This fundamental obstacle to accurate reporting has many adverse consequences for the study and treatment of mental disorders. Better tools for accurate retrospective reporting of mental disorder symptoms have the potential for broad scientific benefits.
We designed a life history calendar (LHC) to support this task, and randomized more than 1000 individuals to each arm of a retrospective diagnostic interview with and without the LHC. We also conducted a careful validation with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition.
Results demonstrate that—just as with frequent measurement longitudinal studies—use of an LHC in retrospective measurement can more than double reports of lifetime experience of some mental disorders.
The LHC significantly improves retrospective reporting of mental disorders. This tool is practical for application in both large cross-sectional surveys of the general population and clinical intake of new patients.
Experiments were conducted at the Upper Coastal Plain Research Station near Rocky Mount and at the Peanut Belt Research Station near Lewiston-Woodville in 2002 and 2003. Peanut injury was minimal (< 5%) with all soil-applied programs. S-Metolachlor PRE alone or in mixture with sulfentrazone, diclosulam, or flumioxazin controlled annual grasses similarly (66 to 87%). The addition of imazapic plus 2,4-DB POST increased annual grass control (> 93%). Sulfentrazone or diclosulam in mixture with S-metolachlor were the best PRE options, with 94% and 92% control of yellow and purple nutsedge, respectively, with flumioxazin being least effective at 70%. Diclosulam and flumioxazin in mixture with S-metolachlor were the best PRE options, with 99% and 93%, respectively for common ragweed control, whereas sulfentrazone was the least effective at 65%. S-Metolachlor in mixture with sulfentrazone, diclosulam, or flumioxazin PRE were similar (87 to 90%) for common lambsquarters control. S-Metolachlor in mixture with sulfentrazone, diclosulam, or flumioxazin provided similar levels of entireleaf, ivyleaf, pitted, and tall morningglory control (87, 86, and 87%, respectively) and better than S-metolachlor alone at 64%. Flumioxazin in mixture with S-metolachlor was the best PRE option for control of Palmer amaranth at 96%, whereas diclosulam with S-metolachlor was the best PRE option for control of eclipta at 100%. The prepackaged mixture of acifluorfen and bentazon plus 2,4-DB POST and imazapic plus 2,4-DB POST were similar for all morningglory species (> 96%) and Palmer amaranth control (93 and 97%, respectively). Peanut treated with S-metolachlor plus diclosulam PRE numerically yielded the highest at 3,210 kg/ha, but were statistically equivalent to S-metolachlor plus flumioxazin PRE at 3,040 kg/ha. Peanut treated with imazapic plus 2,4-DB POST yielded the most at 3,400 kg/ha, while peanut treated with a prepackaged mixture of acifluorfen and bentazon plus 2,4-DB POST yielded less (3,070 kg/ha).
The development and spread of glyphosate-resistant (GR) horseweed has increased the use of dicamba as an alternative herbicide treatment. Research evaluated suspected glyphosate-resistant horseweed populations from DeKalb (GR-1) and Cherokee (GR-2) counties, Alabama, for response to glyphosate, dicamba, and glyphosate + dicamba. Populations used for resistance determination were tested at rosette and bolt growth stages. Glyphosate resistance evaluation treatments ranged from 0 to 36.0 kg ae ha−1. Data confirmed that GR-1 and GR-2 horseweed populations were 3.0 to 38 times more resistant to glyphosate than the susceptible population, according to population, data type, and growth stage at treatment. GR-1 and GR-2 populations were further evaluated for response to dicamba. Dicamba was applied at 0 to 1.12 kg ai ha−1, both with and without the addition of glyphosate at 1.12 kg ae ha−1. All populations had similar tolerance to dicamba, with the exception of GR-2 treated at the rosette growth stage, which had ~2-fold greater tolerance. When glyphosate was tank-mixed with dicamba, the response of GR populations was similar to that of dicamba alone. Therefore, any potential resistance-management benefit of tank-mixing dicamba with glyphosate may be negated when one is attempting to control GR horseweed. Conversely, adding glyphosate to dicamba drastically enhanced control of the susceptible population at both growth stages.
Research was conducted from 2011 to 2014 to determine weed population
dynamics and frequency of glyphosate-resistant (GR) Palmer amaranth with
herbicide programs consisting of glyphosate, dicamba, and residual
herbicides in dicamba-tolerant cotton. Five treatments were maintained in
the same plots over the duration of the experiment: three sequential POST
applications of glyphosate with or without pendimethalin plus diuron PRE;
three sequential POST applications of glyphosate plus dicamba with and
without the PRE herbicides; and a POST application of glyphosate plus
dicamba plus acetochlor followed by one or two POST applications of
glyphosate plus dicamba without PRE herbicides. Additional treatments
included alternating years with three sequential POST applications of
glyphosate only and glyphosate plus dicamba POST with and without PRE
herbicides. The greatest population of Palmer amaranth was observed when
glyphosate was the only POST herbicide throughout the experiment. Although
diuron plus pendimethalin PRE in a program with only glyphosate POST
improved control during the first 2 yr, these herbicides were ineffective by
the final 2 yr on the basis of weed counts from soil cores. The lowest
population of Palmer amaranth was observed when glyphosate plus dicamba were
applied regardless of PRE herbicides or inclusion of acetochlor POST.
Frequency of GR Palmer amaranth was 8% or less when the experiment was
initiated. Frequency of GR Palmer amaranth varied by herbicide program
during 2012 but was similar among all herbicide programs in 2013 and 2014.
Similar frequency of GR Palmer amaranth across all treatments at the end of
the experiment most likely resulted from pollen movement from Palmer
amaranth treated with glyphosate only to any surviving female plants
regardless of PRE or POST treatment. These data suggest that GR Palmer
amaranth can be controlled by dicamba and that dicamba is an effective
alternative mode of action to glyphosate in fields where GR Palmer amaranth
The main question that Firestone & Scholl (F&S) pose is whether “what and how we see is functionally independent from what and how we think, know, desire, act, and so forth” (sect. 2, para. 1). We synthesize a collection of concerns from an interdisciplinary set of coauthors regarding F&S's assumptions and appeals to intuition, resulting in their treatment of visual perception as context-free.
The array seen when saccading across a point light source blinking in the dark is displaced in the direction of the saccade. This displacement reflects an abrupt shift of spatiotopic coordinates that precedes the actual eye movement. The extraretinal signal mediating this discrete shift appears to be an oculomotor reference signal, specifying intended eye orientation, that changes discretely before saccades.
Grush makes extensive use of von Holst and Mittelstaedt's (1950) efference copy hypothesis. Although his embellishment of the model is admirably more sophisticated than that of its progenitors, I argue that it still suffers from the same conceptual limitations as entailed in its original formulation.
Cognitive psychologists tend to treat intentionality as a control variable during experiments, yet ignore it when generating mechanistic descriptions of performance. Wynn's work brings this conflict into striking relief and, when considered in relation to recent neurophysiological findings, makes it clear that intentionality can be regarded mechanistically if one defines it as the planning of distal effects.
Hommel et al. propose that action planning and perception utilize common resources. This implies perception should have intention-relative content. Data supporting this implication are presented. These findings challenge the notion of perception as “seeing.” An alternative is suggested (i.e., perception as distal control) that may provide a means of integrating representational and ecological approaches to the study of organism-environment coordination.
Gold & Stoljar reveal that adherence to the radical neuron
doctrine cannot be maintained via appeals to scientific principles.
Using arguments from (1) naturalism and materialism, (2) unification,
and (3) exemplars, it is shown that the “mind-is-brain”
materialism explicit in the trivial version of the neuron doctrine
ultimately suffers the same theoretical fate. Cognitive science,
if it is to adopt an ontology at all, would be better served by
a metaphysically neutral ontology such as double-aspect theory
or neutral monism.
Ballard et al. model eye position as a deictic pointer for
spatial perception. Evidence from research on gaze control indicates,
however, that shifts in actual eye position are neither necessary nor
sufficient to produce shifts in spatial perception. Deictic context is
instead provided by the interaction between two deictic pointers;
one representing actual eye position, and the other, intended eye
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