153 research outputs found
Testing the Impact of Group Offending on Behavioural Similarity in Serial Robbery
Behavioural case linkage assumes that offenders behave in a similar way across their crimes. However, group offending could impact on behavioural similarity. This study uses robbery data from two police forces to test this by comparing the behavioural similarity of pairs of lone offences (LL), pairs of group offences (GG) and pairs of offences where one crime was committed alone and the other in a group (GL). Behavioural similarity was measured using Jaccard’s coefficients. Kruskal–Wallis tests were used to examine differences between the three categories within the linked samples. No statistically significant differences were found for linked GG compared to linked LL pairs. However, differences emerged between GL and the other categories for some behaviours (especially control) suggesting caution should be applied when linking group and lone offences committed by the same perpetrator. Differences between linked and unlinked pairs were assessed using receiver operating characteristic. The results suggest it is possible to distinguish between linked and unlinked pairs based on behaviour especially within the GG and LL categories. There were, however, fewer significant findings for the GL sample, suggesting there may be issues linking crimes where the offender commits one crime as part of a group and the other alone
Globally weaker and topologically different: resting-state connectivity in youth with autism
Abstract Background There is a lack of agreement about functional connectivity differences in individuals with autism spectrum disorder (ASD). Studies using absolute strength have found reduced connectivity, while those using relative strength––a measure of system topology––reveal mostly enhanced connectivity. We hypothesized that mixed findings may be driven by the metric of functional connectivity. Methods Resting-state echo planar 3 T functional magnetic resonance imaging scans were acquired on a Siemens Verio Scanner from 6 to 17-year-old youth with ASD (n = 81) and a matched typically developing control group (n = 82). All functional time series data were preprocessed using a confound regression procedure that has been previously validated in large-scale developmental datasets. It has also been shown to be highly effective at reducing the influence of motion artifact on connectivity data. We extracted time series data from a 333-node parcellation scheme, which was previously mapped to 13 functional systems. A Pearson’s correlation was calculated and transformed to Fisher’s z between every pair of nodes to create a weighted 333 × 333 adjacency matrix. Mean absolute functional connectivity strength was the mean Fisher’s z of the matrix. Relative functional connectivity was corrected for individual differences in mean absolute functional connectivity (i.e., each connection in the matrix was divided by their mean z), and functional connectivity was evaluated within and across each of the functional networks in the parcellation scheme. Results Absolute functional connectivity strength was lower in ASD, and lower functional connectivity was correlated with greater ASD symptom severity. Relative functional connectivity was higher for the ASD group in the ventral attention and retrosplenial-temporal systems, with lower cross-system functional connectivity between the ventral attention and somatomotor-mouth systems. Functional connectivity within the ventral attention and retro-splenial systems correlated significantly with ASD symptom severity. Conclusions Within a context of globally weaker functional connectivity, youth with ASD have an atypical topology of brain systems that support social perception and communication. This study clarifies the mixed results reported previously and demonstrates that the functional connectivity metric influences the observed direction of functional connectivity differences for individuals with ASD
Effects of empagliflozin on fluid overload, weight and blood pressure in chronic kidney disease
BACKGROUND: Chronic kidney disease (CKD) is associated with fluid excess
which can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived “Fluid Overload” and adiposity in a CKD population.
METHODS: EMPA-KIDNEY was a 6609-participant double-blind placebo-controlled
trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a 660-participant substudy, bioimpedance measurements were added to the main trial procedures at randomization, 2- and 18-month follow-up visits. The substudy’s primary outcome was the study-average difference in absolute “Fluid Overload” (an estimate of excess extracellular water) analyzed using a mixed-model repeated
measures approach.
RESULTS: The 660 substudy participants were broadly representative of the 6609-
participant trial population. Substudy mean baseline absolute “Fluid Overload” was 0.4±1.7 L. Compared to placebo, the overall mean absolute “Fluid Overload” difference among those allocated empagliflozin was -0.24 L (95%CI -0.38, -0.11), with similar-sized differences at 2- and 18-months, and in pre-specified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95%CI -0.69, -0.30, including the -0.24 L “Fluid Overload” difference); and a -0.30 L (95%CI -0.57, -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (- 0.28 [95%CI -1.41, 0.85] kg). The between-group difference in weight was -0.7 kg
(95%CI -1.3, -0.1).
CONCLUSIONS: In a broad range of patients with CKD, empagliflozin resulted in a
sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass
Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?
BACKGROUND Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C- reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN Double-blind, randomized placebo-controlled trial. PATIENTS Fifty women with type 2 diabetes. MEASUREMENTS Classical and novel risk factors for vascular disease. RESULTS Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2.55 to - 0.29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P lt 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed
Ferromagnetic resonators synthesized by metal-organic decomposition epitaxy
Metal-organic decomposition epitaxy is an economical wet-chemical approach suitable to synthesize high-quality low-spin-damping films for resonator and oscillator applications. This work reports the temperature dependence of ferromagnetic resonances and associated structural and magnetic quantities of yttrium iron garnet nanofilms that coincide with single-crystal values. Despite imperfections originating from wet-chemical deposition and spin coating, the quality factor for out-of-plane and in-plane resonances approaches 600 and 1000, respectively, at room temperature and 40 GHz. These values increase with temperature and are 100 times larger than those offered by commercial devices based on complementary metal-oxide semiconductor voltage-controlled oscillators at comparable production costs
Differential engagement of anterior cingulate corte subdivisions for cognitive and emotional function.
Abstract Functional differentiation of dorsal (dACC) and rostral (rACC) anterior cingulate cortex for cognitive and emotional function has received considerable indirect support. Using fMRI, parallel tasks, and within-subject analysis, the present study directly tested the proposed specialization of ACC subdivisions. A Task  Region interaction confirmed more dACC activation during color-word distractors and more rACC activation during emotion-word distractors. Activity in ACC subdivisions differentially predicted behavioral performance. Connectivity with prefrontal and limbic regions also supported distinct dACC and rACC roles. Findings provide direct evidence for differential engagement of ACC subdivisions in cognitive and emotional processing and for differential functional connectivity in the implementation of cognitive control and emotion regulation. Results point to an anatomical and functional continuum rather than segregated operations
Characterization of immunoglobulin G antibodies to Plasmodium falciparum sporozoite surface antigen MB2 in malaria exposed individuals
<p>Abstract</p> <p>Background</p> <p>MB2 protein is a sporozoite surface antigen on the human malaria parasite <it>Plasmodium falciparum</it>. MB2 was identified by screening a <it>P. falciparum </it>sporozoite cDNA expression library using immune sera from a protected donor immunized via the bites of <it>P. falciparum</it>-infected irradiated mosquitoes. It is not known whether natural exposure to <it>P. falciparum </it>also induces the anti-MB2 response and if this response differs from that in protected individuals immunized via the bites of <it>P. falciparum </it>infected irradiated mosquitoes. The anti-MB2 antibody response may be part of a robust protective response against the sporozoite.</p> <p>Methods</p> <p>Fragments of polypeptide regions of MB2 were constructed as recombinant fusions sandwiched between glutathione S-transferase and a hexa histidine tag for bacterial expression. The hexa histidine tag affinity purified proteins were used to immunize rabbits and the polyclonal sera evaluated in an <it>in vitro </it>inhibition of sporozoite invasion assay. The proteins were also used in immunoblots with sera from a limited number of donors immunized via the bites of <it>P. falciparum </it>infected irradiated mosquitoes and plasma and serum obtained from naturally exposed individuals in Kenya.</p> <p>Results</p> <p>Rabbit polyclonal antibodies targeting the non-repeat region of the basic domain of MB2 inhibited sporozoites entry into HepG2-A16 cells <it>in vitro</it>. Analysis of serum from five human volunteers that were immunized via the bites of <it>P. falciparum </it>infected irradiated mosquitoes that developed immunity and were completely protected against subsequent challenge with non-irradiated parasite also had detectable levels of antibody against MB2 basic domain. In contrast, in three volunteers not protected, anti-MB2 antibodies were below the level of detection. Sera from protected volunteers preferentially recognized a non-repeat region of the basic domain of MB2, whereas plasma from naturally-infected individuals also had antibodies that recognize regions of MB2 that contain a repeat motif in immunoblots. Sequence analysis of eleven field isolates and four laboratory strains showed that these antigenic regions of the basic domain of the <it>MB2 </it>gene are highly conserved in parasites obtained from different parts of the world. Moreover, anti-MB2 antibodies also were detected in the plasma of 83% of the individuals living in a malaria endemic area of Kenya (n = 41).</p> <p>Conclusion</p> <p>A preliminary analysis of the human humoral response against MB2 indicates that it may be an additional highly conserved target for immune intervention at the pre-erythrocytic stage of <it>P. falciparum </it>life cycle.</p
Year-long stability of nucleic acid bases in concentrated sulfuric acid: implications for the persistence of organic chemistry in Venus’ clouds
We show that the nucleic acid bases adenine, cytosine, guanine, thymine, and uracil, as well as 2,6-diaminopurine, and the “core” nucleic acid bases purine and pyrimidine, are stable for more than one year in concentrated sulfuric acid at room temperature and at acid concentrations relevant for Venus clouds (81% w/w to 98% w/w acid, the rest water). This work builds on our initial stability studies and is the first ever to test the reactivity and structural integrity of organic molecules subjected to extended incubation in concentrated sulfuric acid. The one-year-long stability of nucleic acid bases supports the notion that the Venus cloud environment—composed of concentrated sulfuric acid—may be able to support complex organic chemicals for extended periods of time
Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials
Background:
Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.
Methods:
In this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56–60 years, 61–65 years, 66–70 years, 71–75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups.
Findings:
14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73–0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73–0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80–0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85–0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.
Interpretation:
Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials.
Funding:
Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation
Stability of nucleic acid bases in concentrated sulfuric acid: Implications for the habitability of Venus'clouds
What constitutes a habitable planet is a frontier to be explored and requires pushing the boundaries of our terracentric viewpoint for what we deem to be a habitable environment. Despite Venus’ 700 K surface temperature being too hot for any plausible solvent and most organic covalent chemistry, Venus’ cloud-filled atmosphere layers at 48 to 60 km above the surface hold the main requirements for life: suitable temperatures for covalent bonds; an energy source (sunlight); and a liquid solvent. Yet, the Venus clouds are widely thought to be incapable of supporting life because the droplets are composed of concentrated liquid sulfuric acid—an aggressive solvent that is assumed to rapidly destroy most biochemicals of life on Earth. Recent work, however, demonstrates that a rich organic chemistry can evolve from simple precursor molecules seeded into concentrated sulfuric acid, a result that is corroborated by domain knowledge in industry that such chemistry leads to complex molecules, including aromatics. We aim to expand the set of molecules known to be stable in concentrated sulfuric acid. Here, we show that nucleic acid bases adenine, cytosine, guanine, thymine, and uracil, as well as 2,6-diaminopurine and the “core” nucleic acid bases purine and pyrimidine, are stable in sulfuric acid in the Venus cloud temperature and sulfuric acid concentration range, using UV spectroscopy and combinations of 1D and 2D 1H 13C 15N NMR spectroscopy. The stability of nucleic acid bases in concentrated sulfuric acid advances the idea that chemistry to support life may exist in the Venus cloud particle environment
- …