Synthetic vs. Real-World Continuous Landscapes: A Local Optima Networks View

Local optima networks (LONs) are a useful tool to analyse and visualise the global structure of fitness landscapes. The main goal of our study is to use LONs to contrast the global structure of synthetic benchmark functions against those of real-world continuous optimisation problems of similar dimensions. We selected two real-world problems, namely, an engineering design problem and a machine learning problem. Our results indicate striking differences in the global structure of synthetic vs real-world problems. The real-world problems studied were easier to solve than the synthetic ones, and our analysis reveals why; they have easier to traverse global structures with fewer nodes and edges, no sub-optimal funnels, higher neutrality and multiple global optima with shorter trajectories towards them

Generating SQL queries from visual specifications

Abstract: Structured Query Language (SQL) is the most widely used declarative language for accessing relational databases, and an essential topic in introductory database courses in higher learning institutions. Despite the intuitiveness of SQL, formulating and comprehending written queries can be confusing, especially for undergraduate students. One major reason for this is that the simple syntax of SQL is often misleading and hard to comprehend. A number of tools have been developed to aid the comprehension of queries and improve the mental models of students concerning the underlying logic of SQL. Some of these tools employed visualisation and animation in their approach to aid the comprehension of SQL. This paper presents an interactive comprehension aid based on visualisation, specifically designed to support the SQL SELECT statement, an area identified in the literature as problematic for students. The visualisation tool uses visual specifications depicting SQL operations to build queries. This is expected to reduce the cognitive load of a student who is learning SQL. We have shown with an online survey that adopting visual specifications in teaching systems assist students in attaining a richer learning experience in introductory database courses

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia

Pharmacology as a foreign language: A preliminary evaluation of podcasting as a supplementary learning tool for non-medical prescribing students

<p>Abstract</p> <p>Background</p> <p>Nurses and other health professionals in the U.K. can gain similar prescribing rights to doctors by undertaking a non-medical prescribing course. Non-medical prescribing students must have a thorough understanding of the pharmacology of prescribing to ensure safe practice. Pharmacology education at this level is complicated by the variation in students' prior subject knowledge of, and anxiety about, the subject. The recent advances in technology, particularly the potential for mobile learning, provide increased opportunities for students to familiarise themselves with lecture materials and hence promote understanding. The objective of this study was therefore to evaluate both the subjective (student perception) and objective (student use and exam results) usefulness of podcasts of pharmacology lectures which were provided as an extra learning tool to two cohorts (n = 69) of non-medical prescribing students.</p> <p>Methods</p> <p>The podcasts were made available to students through the virtual learning environment WebCT. Use of podcasts by two successive cohorts of nurse prescribing students (n = 69) was tracked through WebCT. Survey data, which was collected from 44 of these students, investigated patterns of/reasons for podcast use and perceived usefulness of podcasts as a learning tool. Of these 69 students, 64 completed the pharmacology exam. In order to examine any impact of podcasts on student knowledge, their exam results were compared with those of two historical cohorts who did not have access to podcasts (n = 70).</p> <p>Results</p> <p>WebCT tracking showed that 91% of students accessed at least one podcast. 93% of students used the podcasts to revisit a lecture, 85% used podcasts for revision, and 61% used the podcasts when they had a specific question. Only 22% used the podcasts because they had missed a pharmacology session. Most students (81%) generally listened to the entire podcast rather than specific sections and most (73%) used them while referring to their lecture handouts. The majority of students found the podcasts helpful as a learning tool, as a revision aid and in promoting their understanding of the subject. Evaluation of the range of marks obtained, mode mark and mean mark suggested improved knowledge in students with access to podcasts compared to historical cohorts of students who did not have access to pharmacology podcasts.</p> <p>Conclusions</p> <p>The results of this study suggest that non-medical prescribing students utilised podcasts of pharmacology lectures, and have found the availability of these podcasts helpful for their learning. Exam results indicate that the availability of podcasts was also associated with improved exam performance.</p

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

The test characteristics of head circumference measurements for pathology associated with head enlargement: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The test characteristics of head circumference (HC) measurement percentile criteria for the identification of previously undetected pathology associated with head enlargement in primary care are unknown.</p> <p>Methods</p> <p>Electronic patient records were reviewed to identify children age 3 days to 3 years with new diagnoses of intracranial expansive conditions (IEC) and metabolic and genetic conditions associated with macrocephaly (MGCM). We tested the following HC percentile threshold criteria: ever above the 95^th, 97^th, or 99.6^thpercentile and ever crossing 2, 4, or 6 increasing major percentile lines. The Centers for Disease Control and World Health Organization growth curves were used, as well as the primary care network (PCN) curves previously derived from this cohort.</p> <p>Results</p> <p>Among 74,428 subjects, 85 (0.11%) had a new diagnosis of IEC (n = 56) or MGCM (n = 29), and between these 2 groups, 24 received intervention. The 99.6^thpercentile of the PCN curve was the only threshold with a PPV over 1% (PPV 1.8%); the sensitivity of this threshold was only 15%. Test characteristics for the 95th percentiles were: sensitivity (CDC: 46%; WHO: 55%; PCN: 40%), positive predictive value (PPV: CDC: 0.3%; WHO: 0.3%; PCN: 0.4%), and likelihood ratios positive (LR+: CDC: 2.8; WHO: 2.2; PCN: 3.9). Test characteristics for the 97th percentiles were: sensitivity (CDC: 40%; WHO: 48%; PCN: 34%), PPV (CDC: 0.4%; WHO: 0.3%; PCN: 0.6%), and LR+ (CDC: 3.6; WHO: 2.7; PCN: 5.6). Test characteristics for crossing 2 increasing major percentile lines were: sensitivity (CDC: 60%; WHO: 40%; PCN: 31%), PPV (CDC: 0.2%; WHO: 0.1%; PCN: 0.2%), and LR+ (CDC: 1.3; WHO: 1.1; PCN: 1.5).</p> <p>Conclusions</p> <p>Commonly used HC percentile thresholds had low sensitivity and low positive predictive value for diagnosing new pathology associated with head enlargement in children in a primary care network.</p

Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3,4,5,6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P &lt; 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD

ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways