Non-polynomial Worst-Case Analysis of Recursive Programs

We study the problem of developing efficient approaches for proving worst-case bounds of non-deterministic recursive programs. Ranking functions are sound and complete for proving termination and worst-case bounds of nonrecursive programs. First, we apply ranking functions to recursion, resulting in measure functions. We show that measure functions provide a sound and complete approach to prove worst-case bounds of non-deterministic recursive programs. Our second contribution is the synthesis of measure functions in nonpolynomial forms. We show that non-polynomial measure functions with logarithm and exponentiation can be synthesized through abstraction of logarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem using linear programming. While previous methods obtain worst-case polynomial bounds, our approach can synthesize bounds of the form $\mathcal{O}(n\log n)$ as well as $\mathcal{O}(n^r)$ where $r$ is not an integer. We present experimental results to demonstrate that our approach can obtain efficiently worst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the divide-and-conquer algorithm for the Closest-Pair problem, where we obtain $\mathcal{O}(n \log n)$ worst-case bound, and (ii) Karatsuba's algorithm for polynomial multiplication and Strassen's algorithm for matrix multiplication, where we obtain $\mathcal{O}(n^r)$ bound such that $r$ is not an integer and close to the best-known bounds for the respective algorithms.Comment: 54 Pages, Full Version to CAV 201

Dermatological remedies in the traditional pharmacopoeia of Vulture-Alto Bradano, inland southern Italy

Dermatological remedies make up at least one-third of the traditional pharmacopoeia in southern Italy. The identification of folk remedies for the skin is important both for the preservation of traditional medical knowledge and in the search for novel antimicrobial agents in the treatment of skin and soft tissue infection (SSTI). Our goal is to document traditional remedies from botanical, animal, mineral and industrial sources for the topical treatment of skin ailments. In addition to SSTI remedies for humans, we also discuss certain ethnoveterinary applications. Field research was conducted in ten communities in the Vulture-Alto Bradano area of the Basilicata province, southern Italy. We randomly sampled 112 interviewees, stratified by age and gender. After obtaining prior informed consent, we collected data through semi-structured interviews, participant-observation, and small focus groups techniques. Voucher specimens of all cited botanic species were deposited at FTG and HLUC herbaria located in the US and Italy. We report the preparation and topical application of 116 remedies derived from 38 plant species. Remedies are used to treat laceration, burn wound, wart, inflammation, rash, dental abscess, furuncle, dermatitis, and other conditions. The pharmacopoeia also includes 49 animal remedies derived from sources such as pigs, slugs, and humans. Ethnoveterinary medicine, which incorporates both animal and plant derived remedies, is addressed. We also examine the recent decline in knowledge regarding the dermatological pharmacopoeia. The traditional dermatological pharmacopoeia of Vulture-Alto Bradano is based on a dynamic folk medical construct of natural and spiritual illness and healing. Remedies are used to treat more than 45 skin and soft tissue conditions of both humans and animals. Of the total 165 remedies reported, 110 have never before been published in the mainland southern Italian ethnomedical literature

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Host Immune Response to Mosquito-Transmitted Chikungunya Virus Differs from That Elicited by Needle Inoculated Virus

Mosquito-borne diseases are a worldwide public health threat. Mosquitoes transmit viruses or parasites during feeding, along with salivary proteins that modulate host responses to facilitate both blood feeding and pathogen transmission. Understanding these earliest events in mosquito transmission of arboviruses by mosquitoes is essential for development and assessment of rational vaccine and treatment strategies. In this report, we compared host immune responses to chikungunya virus (CHIKV) transmission by (1) mosquito bite, or (2) by needle inoculation.Differential cytokine expression was measured using quantitative real-time RT-PCR, at sites of uninfected mosquito bites, CHIKV-infected mosquito bites, and needle-inoculated CHIKV. Both uninfected and CHIKV infected mosquitoes polarized host cytokine response to a TH2 profile. Compared to uninfected mosquito bites, expression of IL-4 induced by CHIKV-infected mosquitoes were 150 fold and 527.1 fold higher at 3 hours post feeding (hpf) and 6 hpf, respectively. A significant suppression of TH1 cytokines and TLR-3 was also observed. These significant differences may result from variation in the composition of uninfected and CHIKV-infected mosquito saliva. Needle injected CHIKV induced a robust interferon-gamma, no detectable IL-4, and a significant up-regulation of TLR-3.This report describes the first analysis of cutaneous cytokines in mice bitten by CHIKV-infected mosquitoes. Our data demonstrate contrasting immune activation in the response to CHIKV infection by mosquito bite or needle inoculation. The significant role of mosquito saliva in these earliest events of CHIKV transmission and infection are highlighted

Activity profiles of elite wheelchair rugby players during competition

To quantify the activity profiles of elite wheelchair rugby and establish classification-specific arbitrary speed zones. Additionally, indicators of fatigue during full matches were explored. Methods: Seventy-five elite wheelchair rugby players from eleven national teams were monitored using a radio-frequency based, indoor tracking system across two international tournaments. Players who participated in complete quarters (n = 75) and full matches (n = 25) were included and grouped by their International Wheelchair Rugby Federation functional classification: group I (0-0.5), II (1.0-1.5), III (2.0-2.5) and IV (3.0-3.5). Results: During a typical quarter, significant increases in total distance (m), relative distance (m·minˉ¹), and mean speed (m·sˉ¹) were associated with an increase in classification group (P < 0.001), with the exception of group III and IV. However, group IV players achieved significantly higher peak speeds (3.82 ± 0.31 m·sˉ¹) than groups I (2.99 ± 0.28 m·sˉ¹), II (3.44 ± 0.26 m·sˉ¹) and III (3.67 ± 0.32 m·sˉ¹). Groups I and II differed significantly in match intensity during very low/low speed zones and the number of high-intensity activities in comparison with groups III and IV (P < 0.001). Full match analysis revealed that activity profiles did not differ significantly between quarters. Conclusions: Notable differences in the volume of activity were displayed across the functional classification groups. However, the specific on-court requirements of defensive (I and II) and offensive (III and IV) match roles appeared to influence the intensity of match activities and consequently training prescription should be structured accordingly

Determinants of cognitive function in childhood: A cohort study in a middle income context

BACKGROUND: There is evidence that poverty, health and nutrition affect children's cognitive development. This study aimed to examine the relative contributions of both proximal and distal risk factors on child cognitive development, by breaking down the possible causal pathways through which poverty affects cognition. METHODS: This cohort study collected data on family socioeconomic status, household and neighbourhood environmental conditions, child health and nutritional status, psychosocial stimulation and nursery school attendance. The effect of these on Wechsler Pre-School and Primary Scale of Intelligence scores at five years of age was investigated using a multivariable hierarchical analysis, guided by the proposed conceptual framework. RESULTS: Unfavourable socioeconomic conditions, poorly educated mother, absent father, poor sanitary conditions at home and in the neighbourhood and low birth weight were negatively associated with cognitive performance at five years of age, while strong positive associations were found with high levels of domestic stimulation and nursery school attendance. CONCLUSION: Children's cognitive development in urban contexts in developing countries could be substantially increased by interventions promoting early psychosocial stimulation and preschool experience, together with efforts to prevent low birth weight and promote adequate nutritional status

Desynchronization of Diurnal Rhythms in Bipolar Disorder and Borderline Personality Disorder

It has long been proposed that diurnal rhythms are disturbed in bipolar disorder (BD). Such changes are obvious in episodes of mania or depression. However, detailed study of patients between episodes has been rare and comparison with other psychiatric disorders rarer still. Our hypothesis was that evidence for desynchronization of diurnal rhythms would be evident in BD and that we could test the specificity of any effect by studying borderline personality disorder (BPD). Individuals with BD (n = 36), BPD (n = 22) and healthy volunteers (HC, n = 25) wore a portable heart rate and actigraphy device and used a smart-phone to record self-assessed mood scores 10 times per day for 1 week. Average diurnal patterns of heart rate (HR), activity and sleep were compared within and across groups. Desynchronization in the phase of diurnal rhythms of HR compared with activity were found in BPD (+3 h) and BD (+1 h), but not in HC. A clear diurnal pattern for positive mood was found in all subject groups. The coherence between negative and irritable mood and HR showed a four-cycle per day component in BD and BPD, which was not present in HC. The findings highlight marked de-synchronisation of measured diurnal function in both BD but particularly BPD and suggest an increased association with negative and irritable mood at ultradian frequencies. These findings enhance our understanding of the underlying physiological changes associated with BPD and BD, and suggest objective markers for monitoring and potential treatment targets. Improved mood stabilisation is a translational objective for management of both patient groups

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data