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Background: Recent research has demonstrated that DBS sites in Alzheimer’s (AD) and Parkinson’s (PD) influencing cognition are functionally connected to the subiculum. However, the results are mixed, and it is unclear how or if DBS site-subiculum connectivity can be optimized to improve patient cognition. Methods: We studied how subiculum connectivity influenced cognitive outcomes in both PD (subthalamic nucleus) and AD (fornix) DBS patients (total n = 110). We first confirmed DBS site-subiculum connectivity had opposite cognitive effects in each disease. We next investigated patient factors underlying these opposing effects. Lastly, we related our findings back to clinical practice to guide DBS programming in PD and AD. Results: DBS site-subiculum connectivity correlated with cognitive improvement in AD but decline in PD. This was dependent upon hippocampal atrophy; such that higher subiculum connectivity was beneficial when the hippocampus was atrophic but deleterious when it was intact. Finally, we related our findings back to anatomy with cadaveric dissections and present how DBS stimulation can be optimized to improve patient cognition. Conclusions: DBS site-subiculum connectivity influences cognition but depends on patient factors. Thus, to optimize cognition based on patient factors, DBS electrodes can be programmed to stimulate subregions with higher or lower subiculum connectivity.
The clinical high risk for psychosis (CHR-p) syndrome enables early identification of individuals at risk of schizophrenia and related disorders. We differentiate between the stigma associated with the at-risk identification itself (‘labelling-related’ stigma) versus stigma attributed to experiencing mental health symptoms (‘symptom-related’ stigma) and examine their relationships with key psychosocial variables.
Aims
We compare labelling- and symptom-related stigma in rates of endorsement and associations with self-esteem, social support loss and quality of life.
Method
We assessed stigma domains of shame-related emotions, secrecy and experienced discrimination for both types of stigma. Individuals at CHR-p were recruited across three sites (N = 150); primary analyses included those who endorsed awareness of psychosis risk (n = 113). Paired-sample t-tests examined differences in labelling- versus symptom-related stigma; regressions examined associations with psychosocial variables, controlling for covariates, including CHR-p symptoms.
Results
Respondents reported greater symptom-related shame, but more labelling-related secrecy. Of the nine significant associations between stigma and psychosocial variables, eight were attributable to symptom-related stigma, even after adjusting for CHR-p symptoms.
Conclusions
Stigma attributed to symptoms had a stronger negative association with psychosocial variables than did labelling-related stigma among individuals recently identified as CHR-p. That secrecy related to the CHR-p designation was greater than its symptom-related counterpart suggests that labelling-related stigma may still be problematic for some CHR-p participants. To optimise this pivotal early intervention effort, interventions should address the holistic ‘stigmatising experience’ of having symptoms, namely any harmful reactions received as well as participants’ socially influenced concerns about what their experiences mean, in addition to the symptoms themselves.
Traditionally, primate cognition research has been conducted by independent teams on small populations of a few species. Such limited variation and small sample sizes pose problems that prevent us from reconstructing the evolutionary history of primate cognition. In this chapter, we discuss how large-scale collaboration, a research model successfully implemented in other fields, makes it possible to obtain the large and diverse datasets needed to conduct robust comparative analysis of primate cognitive abilities. We discuss the advantages and challenges of large-scale collaborations and argue for the need for more open science practices in the field. We describe these collaborative projects in psychology and primatology and introduce ManyPrimates as the first, successful collaboration that has established an infrastructure for large-scale, inclusive research in primate cognition. Considering examples of large-scale collaborations both in primatology and psychology, we conclude that this type of research model is feasible and has the potential to address otherwise unattainable questions in primate cognition.
Replication is an important tool used to test and develop scientific theories. Areas of biomedical and psychological research have experienced a replication crisis, in which many published findings failed to replicate. Following this, many other scientific disciplines have been interested in the robustness of their own findings. This chapter examines replication in primate cognitive studies. First, it discusses the frequency and success of replication studies in primate cognition and explores the challenges researchers face when designing and interpreting replication studies across the wide range of research designs used across the field. Next, it discusses the type of research that can probe the robustness of published findings, especially when replication studies are difficult to perform. The chapter concludes with a discussion of different roles that replication can have in primate cognition research.
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to determine if two weeks of excess fructose consumption significantly alters gut microbiota or permeability in humans.
Methods:
We performed a pilot double-blind, cross-over, metabolic unit study in 10 subjects with obesity (body mass index [BMI] 30–40 mg/kg/m2). Each arm provided 75 grams of either fructose or glucose added to subjects’ individual diets for 14 days, substituted isocalorically for complex carbohydrates, with a 19-day wash-out period between arms. Total fructose intake provided in the fructose arm of the study totaled a mean of 20.1% of calories. Outcome measures included fecal microbiota distribution, fecal metabolites, intestinal permeability, markers of endotoxemia, and plasma metabolites.
Results:
Routine blood, uric acid, liver function, and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation, and plasma metabolites were essentially unchanged by either intervention.
Conclusions:
In contrast to rodent preclinical findings, excess fructose did not cause changes in the gut microbiome, metabolome, and permeability as well as endotoxemia in humans with obesity fed fructose for 14 days in amounts known to enhance NAFLD.
European orthohantaviruses (Puumala orthohantavirus (PUUV); Dobrava-Belgrade orthohantavirus (DOBV), genotype Kurkino; Tula orthohantavirus (TULV)), and Leptospira spp. are small mammal-associated zoonotic pathogens that cause diseases with potentially similar symptoms in humans. We investigated the frequency of Leptospira spp. and hantavirus single and double infections in small mammals from 22 sites in Thuringia, central Germany, during 2017. TULV infections were detected at 18 of 22 sites (mean prevalence 13.8%, 93/674). PUUV infections were detected at four of 22 sites (mean prevalence 1.5%, 7/471), and respective PUUV sequences formed a novel phylogenetic clade, but DOBV infections were not detected at all. Leptospira infections were detected at 21 of 22 sites with the highest overall prevalence in field voles (Microtus agrestis) with 54.5% (6/11) and common voles (Microtus arvalis) with 30.3% (205/676). Leptospira–hantavirus coinfections were found in 6.6% (44/671) of common voles but only in two of 395 bank voles. TULV and Leptospira coinfection probability in common voles was driven by individual (age) and population-level factors. Coinfections seemed to be particularly associated with sites where Leptospira spp. prevalence exceeded 35%. Future investigations should evaluate public health consequences of this strong spatial clustering of coinfections.
To compare neuropsychological functions of individuals at risk (IR) for psychosis and patients with a first episode of psychosis (FE) with healthy control subjects (HC). And to determine cognitive factors which have the potential to discriminate IR with (IRtrans) and without (IRnon-trans) transition to psychosis.
Methods
N = 60 prodromal IR and N = 51 healthy control subjects were assessed with a comprehensive neuropsychological test battery. Besides general intelligence the test battery covered two functional domains (executive and attentional functions) and working memory. Within a follow up period of at least 30 month N = 19 IR transited to psychosis and N = 30 IR still have been followed up.
For each patient group (FE and IR), cognitive profiles were constructed by means of z-values adjusted for demographic and medication influence. The HC mean performance level was used as baseline of each group profile. A further profile was constructed by differential values considering IRtrans versus IRnon-trans. Comparisons were carried out by MANOVA and post- hoc t-tests.
Results
In all functional domains FE and IR performed below HC except for specific sustained attention measures. There were no significant differences between FE and IR.
Executive functions and working memory measures were more compromised in IRtrans as compared to IRnon-trans.
Conclusions
Neuropsychological deficiencies precede psychotic breakdown. This indicates that neuropsychological assessments of affected domains may support early detection of psychosis.
The adoption of chemical fallow rotations in Pacific Northwest dryland winter wheat production has caused a weed species composition shift in which scouringrush has established in production fields. Thus, there has been interest in identifying herbicides that effectively control scouringrush in winter wheat–chemical fallow cropping systems. Field experiments were established in growers’ fields near Reardan, WA, in 2014, and The Dalles, OR, in 2015. Ten herbicide treatments were applied to mowed and nonmowed plots during chemical fallow rotations. Scouringrush stem densities were quantified the following spring and after wheat harvest at both locations. Chlorsulfuron plus MCPA-ester resulted in nearly 100% control of scouringrush through wheat harvest. Before herbicide application, mowing had no effect on herbicide efficacy. We conclude chlorsulfuron plus MCPA-ester is a commercially acceptable treatment for smooth and intermediate scouringrush control in winter wheat–chemical fallow cropping systems; however, the lack of a positive yield response when scouringrushes were controlled should factor into management decisions.
The persistence of five herbicides in six soils across Nebraska can be ranked from greatest to least as follows: 5-bromo-3-isopropyl-6-methyluracil (isocil) at 5 and 25 1b/A, 2-chloro-4,6-bis-(isopropylamino)-s-triazine (propazine) at 3 and 9 1b/A, 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (atrazine) at 3 and 9 1b/A, trichlorobenzyl chloride (hereinafter referred to as TCBC) at 7 and 49 1b/A, and 3-(3,4-dichlorophenyl)-1-methoxyl-1-methylurea (linuron) at 3 and 9 1b/A. Soil texture differences (sandy loam, very fine sandy loam, silt loam, and silty clay loam) had a greater influence on herbicide residue carryover than did climatic differences across Nebraska during 1962 to 1968. Soil carryover of herbicide residues was greater in coarse rather than fine-textured soils and in the drier regions of western than in eastern Nebraska. Leaching of herbicides into the soil profile was an avenue of herbicide dissipation.
Crop yield loss–weed density relationships critically influence calculation of economic thresholds and the resulting management recommendations made by a bioeconomic model. To examine site-to-site and year-to-year variation in winter Triticum aestivum L. (winter wheat)–Aegilops cylindrica Host. (jointed goatgrass) interference relationships, the rectangular hyperbolic yield loss function was fit to data sets from multiyear field experiments conducted at Colorado, Idaho, Kansas, Montana, Nebraska, Utah, Washington, and Wyoming. The model was fit to three measures of A. cylindrica density: fall seedling, spring seedling, and reproductive tiller densities. Two parameters: i, the slope of the yield loss curve as A. cylindrica density approaches zero, and a, the maximum percentage yield loss as A. cylindrica density becomes very large, were estimated for each data set using nonlinear regression. Fit of the model to the data was better using spring seedling densities than fall seedling densities, but it was similar for spring seedling and reproductive tiller densities based on the residual mean square (RMS) values. Yield loss functions were less variable among years within a site than among sites for all measures of weed density. For the one site where year-to-year variation was observed (Archer, WY), parameter a varied significantly among years, but parameter i did not. Yield loss functions differed significantly among sites for 7 of 10 comparisons. Site-to-site statistical differences were generally due to variation in estimates of parameter i. Site-to-site and year-to-year variation in winter T. aestivum–A. cylindrica yield loss parameter estimates indicated that management recommendations made by a bioeconomic model cannot be based on a single yield loss function with the same parameter values for the winter T. aestivum-producing region. The predictive ability of a bioeconomic model is likely to be improved when yield loss functions incorporating time of emergence and crop density are built into the model's structure.
The effects of the dimethylamine salt of dicamba (3,6-dichloro-2-methoxybenzoic acid) and the dimethylamine salt of 2,4-D [(2,4-dichlorophenoxy)acetic acid] on fieldbeans (Phaseolus vulgaris L. ‘Great Northern Valley’) were studied in order to assess the potential hazards of using these herbicides in areas adjoining fieldbean production. Dicamba and 2,4-D were applied to fieldbeans at three different rates (1.1, 11.2, and 112.5 g ai/ha) and four different growth stages (preemergence, second trifoliolate leaf, early bloom, and early pod). Application of 2,4-D preemergence or in the second trifoliolate leaf stage of growth did not reduce seed yield, delay maturity, or reduce germination of seed obtained from treated plants. Dicamba or 2,4-D applied at 112.5 g/ha to fieldbeans in the early bloom or early pod stages of growth consistently reduced seed yield, delayed maturity, and reduced germination percentage. Fieldbeans exhibited a greater overall sensitivity to dicamba than to 2,4-D.
Field studies were conducted in 2003 and 2004 near Scottsbluff and Sidney, NE, to identify efficacious chemical weed-control options for irrigated and dryland chickpea production. Weed control had a greater relative effect on chickpea yield in the irrigated system than the dryland system, with yield from the hand-weeded check exceeding the nontreated check by 1,500% in the irrigated system and 87% in the dryland system. Imazethapyr, applied preemergence at the rate of 0.053 kg ai/ha, reduced plant height, delayed plant maturity, and caused leaf chlorosis. At Scottsbluff, preplant-incorporated ethalfluralin caused significant crop injury in 2003, but the ethalfluralin treatment also maintained weed densities 4 wk after crop emergence that were not significantly different than the hand-weeded check at both locations in 2003 and 2004. Treatments containing sulfentrazone provided a similar level of weed control but without any evidence of crop injury. Pendimethalin and pendimethalin + dimethenamid-P applied preemergence provided acceptable weed control in the irrigated system, where water was applied within 4 d after herbicide application, but did not provide acceptable control in the dryland system.
Three models that empirically predict crop yield from crop and weed density were evaluated for their fit to 30 data sets from multistate, multiyear winter wheat–jointed goatgrass interference experiments. The purpose of the evaluation was to identify which model would generally perform best for the prediction of yield (damage function) in a bioeconomic model and which model would best fulfill criteria for hypothesis testing with limited amounts of data. Seven criteria were used to assess the fit of the models to the data. Overall, Model 2 provided the best statistical description of the data. Model 2 regressions were most often statistically significant, as indicated by approximate F tests, explained the largest proportion of total variation about the mean, gave the smallest residual sum of squares, and returned residuals with random distribution more often than Models 1 and 3. Model 2 performed less well based on the remaining criteria. Model 3 outperformed Models 1 and 2 in the number of parameters estimated that were statistically significant. Model 1 outperformed Models 2 and 3 in the proportion of regressions that converged on a solution and more readily exhibited an asymptotic relationship between winter wheat yield and both winter wheat and jointed goatgrass density under the constraint of limited data. In contrast, Model 2 exhibited a relatively linear relationship between yield and crop density and little effect of increasing jointed goatgrass density on yield, thus overpredicting yield at high weed densities when data were scarce. Model 2 had statistical properties that made it superior for hypothesis testing; however, Model 1's properties were determined superior for the damage function in the winter wheat–jointed goatgrass bioeconomic model because it was less likely to cause bias in yield predictions based on data sets of minimum size.
Animal health surveillance enables the detection and control of animal diseases including zoonoses. Under the EU-FP7 project RISKSUR, a survey was conducted in 11 EU Member States and Switzerland to describe active surveillance components in 2011 managed by the public or private sector and identify gaps and opportunities. Information was collected about hazard, target population, geographical focus, legal obligation, management, surveillance design, risk-based sampling, and multi-hazard surveillance. Two countries were excluded due to incompleteness of data. Most of the 664 components targeted cattle (26·7%), pigs (17·5%) or poultry (16·0%). The most common surveillance objectives were demonstrating freedom from disease (43·8%) and case detection (26·8%). Over half of components applied risk-based sampling (57·1%), but mainly focused on a single population stratum (targeted risk-based) rather than differentiating between risk levels of different strata (stratified risk-based). About a third of components were multi-hazard (37·3%). Both risk-based sampling and multi-hazard surveillance were used more frequently in privately funded components. The study identified several gaps (e.g. lack of systematic documentation, inconsistent application of terminology) and opportunities (e.g. stratified risk-based sampling). The greater flexibility provided by the new EU Animal Health Law means that systematic evaluation of surveillance alternatives will be required to optimize cost-effectiveness.
Puumala virus (PUUV) causes many human infections in large parts of Europe and can lead to mild to moderate disease. The bank vole (Myodes glareolus) is the only reservoir of PUUV in Central Europe. A commercial PUUV rapid field test for rodents was validated for bank-vole blood samples collected in two PUUV-endemic regions in Germany (North Rhine-Westphalia and Baden-Württemberg). A comparison of the results of the rapid field test and standard ELISAs indicated a test efficacy of 93–95%, largely independent of the origin of the antigens used in the ELISA. In ELISAs, reactivity for the German PUUV strain was higher compared to the Swedish strain but not compared to the Finnish strain, which was used for the rapid field test. In conclusion, the use of the rapid field test can facilitate short-term estimation of PUUV seroprevalence in bank-vole populations in Germany and can aid in assessing human PUUV infection risk.
In August 2012, an explosive outbreak of severe lower respiratory tract infection (LRTI) due to Streptococcus pneumoniae serotype-8 occurred in a highly vaccinated elderly institutionalized population in England. Fifteen of 23 residents developed LRTI over 4 days (attack rate 65%); 11 had confirmed S. pneumoniae serotype-8 disease, and two died. Following amoxicillin chemoprophylaxis and pneumococcal polysaccharide vaccine (PPV) re-vaccination no further cases occurred in the following 2 months. No association was found between being an outbreak-associated case and age (P = 0·36), underlying comorbidities [relative risk (RR) 0·84 95% confidence interval (CI) 0·34–2·09], or prior receipt of PPV (RR 1·4, 95% CI 0·60–3·33). However, the median number of years since PPV was significantly higher for cases (n = 15, 10·2 years, range 7·3–17·9 years) than non-cases (n = 8, 7·2 years, range 6·8–12·8 years) (P = 0·045), provided evidence of waning immunity. Alternative vaccination strategies should be considered to prevent future S. pneumoniae outbreaks in institutionalized elderly populations.
There is increasing demand for the implementation of effects-based monitoring and surveillance (EBMS) approaches in the Great Lakes Basin to complement traditional chemical monitoring. Herein, we describe an ongoing multiagency effort to develop and implement EBMS tools, particularly with regard to monitoring potentially toxic chemicals and assessing Areas of Concern (AOCs), as envisioned by the Great Lakes Restoration Initiative (GLRI). Our strategy includes use of both targeted and open-ended/discovery techniques, as appropriate to the amount of information available, to guide a priori end point and/or assay selection. Specifically, a combination of in vivo and in vitro tools is employed by using both wild and caged fish (in vivo), and a variety of receptor- and cell-based assays (in vitro). We employ a work flow that progressively emphasizes in vitro tools for long-term or high-intensity monitoring because of their greater practicality (e.g., lower cost, labor) and relying on in vivo assays for initial surveillance and verification. Our strategy takes advantage of the strengths of a diversity of tools, balancing the depth, breadth, and specificity of information they provide against their costs, transferability, and practicality. Finally, a series of illustrative scenarios is examined that align EBMS options with management goals to illustrate the adaptability and scaling of EBMS approaches and how they can be used in management decisions.