Regression with Empirical Variable Selection: Description of a New Method and Application to Ecological Datasets

Despite recent papers on problems associated with full-model and stepwise regression, their use is still common throughout ecological and environmental disciplines. Alternative approaches, including generating multiple models and comparing them post-hoc using techniques such as Akaike's Information Criterion (AIC), are becoming more popular. However, these are problematic when there are numerous independent variables and interpretation is often difficult when competing models contain many different variables and combinations of variables. Here, we detail a new approach, REVS (Regression with Empirical Variable Selection), which uses all-subsets regression to quantify empirical support for every independent variable. A series of models is created; the first containing the variable with most empirical support, the second containing the first variable and the next most-supported, and so on. The comparatively small number of resultant models (n = the number of predictor variables) means that post-hoc comparison is comparatively quick and easy. When tested on a real dataset – habitat and offspring quality in the great tit (Parus major) – the optimal REVS model explained more variance (higher R2), was more parsimonious (lower AIC), and had greater significance (lower P values), than full, stepwise or all-subsets models; it also had higher predictive accuracy based on split-sample validation. Testing REVS on ten further datasets suggested that this is typical, with R2 values being higher than full or stepwise models (mean improvement = 31% and 7%, respectively). Results are ecologically intuitive as even when there are several competing models, they share a set of “core” variables and differ only in presence/absence of one or two additional variables. We conclude that REVS is useful for analysing complex datasets, including those in ecology and environmental disciplines

Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Calcium/Calmodulin-Dependent Protein Kinase II Mediates Hippocampal Glutamatergic Plasticity During Benzodiazepine Withdrawal

Benzodiazepine withdrawal anxiety is associated with potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal neurons attributable to increased synaptic incorporation of GluA1-containing AMPARs. The contribution of calcium/calmodulin-dependent protein kinase II (CaMKII) to enhanced glutamatergic synaptic strength during withdrawal from 1-week oral flurazepam (FZP) administration was further examined in hippocampal slices. As earlier reported, AMPAR-mediated miniature excitatory postsynaptic current (mEPSC) amplitude increased in CA1 neurons from 1- and 2-day FZP-withdrawn rats, along with increased single-channel conductance in neurons from 2-day rats, estimated by non-stationary noise analysis. Input–output curve slope was increased without a change in paired-pulse facilitation, suggesting increased AMPAR postsynaptic efficacy rather than altered glutamate release. The increased mEPSC amplitude and AMPAR conductance were related to CaMKII activity, as intracellular inclusion of CaMKIINtide or autocamtide-2-related inhibitory peptide, but not scrambled peptide, prevented both AMPAR amplitude and conductance changes. mEPSC inhibition by 1-naphthyl acetyl spermine and the negative shift in rectification index at both withdrawal time points were consistent with functional incorporation of GluA2-lacking AMPARs. GluA1 but not GluA2 or GluA3 levels were increased in immunoblots of postsynaptic density (PSD)-enriched subcellular fractions of CA1 minislices from 1-day FZP-withdrawn rats, when mEPSC amplitude, but not conductance, was increased. Both GluA1 expression levels and CaMKIIα-mediated GluA1 Ser831 phosphorylation were increased in PSD-subfractions from 2-day FZP-withdrawn rats. As phospho-Thr286CaMKIIα was unchanged, CaMKIIα may be activated through an alternative signaling pathway. Synaptic insertion and subsequent CaMKIIα-mediated Ser831 phosphorylation of GluA1 homomers contribute to benzodiazepine withdrawal-induced AMPAR potentiation and may represent an important hippocampal pathway mediating both drug-induced and activity-dependent plasticity

Differential effects of two chronic diazepam treatment regimes on withdrawal anxiety and aMPA receptor characteristics

Withdrawal from chronic benzodiazepines is associated with increased anxiety and seizure susceptibility. Neuroadaptive changes in neural activity occur in limbo-cortical structures although changes at the level of the GABAA receptor do not provide an adequate explanation for these functional changes. We have employed two diazepam treatment regimes known to produce differing effects on withdrawal aversion in the rat and examined whether withdrawal-induced anxiety was accompanied by changes in AMPA receptor characteristics. Rats were given 28 days treatment with diazepam by the intraperitoneal (i.p.) route (5 mg/kg) and the subcutaneous (s.c.) route (15 mg/kg). Withdrawal anxiety in the elevated plus maze was evident in the group withdrawn from chronic s.c. diazepam (relatively more stable plasma levels) but not from the chronic i.p. group (fluctuating daily plasma levels). In the brains of these rats, withdrawal anxiety was accompanied by increased [3H]Ro48 8587 binding in the hippocampus and thalamus, and decreased GluR1 and GluR2 subunit mRNA expression in the amygdala (GluR1 and GluR2) and cortex (GluR1). The pattern of changes was different in the chronic i.p. group where in contrast to the chronic s.c. group, there was reduced [3H]Ro48 8587 binding in the hippocampus and no alterations in GluR1 and GluR2 subunit expression in the amygdala. While both groups showed reduced GluR1 mRNA subunit expression in the cortex overall, only the agranular insular cortex exhibited marked reductions following chronic i.p. diazepam. Striatal GluR2 mRNA expression was increased in the i.p. group but not the s.c. group. Taken together, these data are consistent with differential neuroadaptive processes in AMPA receptor plasticity being important in withdrawal from chronic benzodiazepines. Moreover, these processes may differ both at a regional and receptor function level according to the behavioral manifestations of withdrawal