Kyphosis and 3-year fall risk in community-dwelling older men.

Hyperkyhosis is thought to be a fall risk factor in older adults. This large study of older men found that fall risk increased with greater kyphosis measured with the blocks method, but did not find an association between kyphosis and falls when measured by the commonly used the Cobb angle method. INTRODUCTION: Research suggests an association between hyperkyphosis and falls in community-dwelling older adults, though this has not been investigated within large, population-based studies. This study sought to determine whether two measures of kyphosis prospectively predict fall risk over 3 years among older men. METHODS: Within the Osteoporotic Fractures in Men Study (MrOS), we conducted two 3-year prospective studies of 2346 and 2928 men. The first group had kyphosis measured by the Cobb angle at visit 1, while the second group had kyphosis assessed with the blocks method at visit 3; both groups then self-reported falls tri-annually for 3 years. Poisson regression with GEE was used to obtain relative risks (RR) of falls. RESULTS: The fall rates over 3 years were 651/1000 person-years among the visit 1 sample (mean age 74 ± 6 years) and 839/1000 person-years among the visit 3 sample (mean age 79 ± 5 years). In adjusted models of the visit 3 sample, the risk of falls was increased by 12% for each standard deviation increase (1.4 blocks) in the number of blocks required to achieve a neutral head and neck position (RR = 1.12, 95% CI = 1.06, 1.18). The Cobb angle was not associated with falls in the visit 1 sample. CONCLUSIONS: Although the Cobb angle did not predict falls in community-dwelling older men over 3 years, the blocks method of measuring kyphosis was predictive of falls in this population. This difference could be due to the Cobb angle's focus on thoracic kyphosis, whereas the blocks method may additionally capture abnormal cervical spine curvature.

A Standardized Approach to Cesarean Surgical Technique and Its Effect on Operative Time and Surgical Morbidity.

OBJECTIVE: To evaluate the impact of a standardized surgical technique for primary cesarean deliveries (CDs) on operative time and surgical morbidity. MATERIALS AND METHODS: Two-year retrospective chart review of primary CD performed around the implementation of a standardized CD surgical technique. The primary outcome was total operative time (TOT). Secondary outcomes included incision-to-delivery time (ITDT), surgical site infection, blood loss, and maternal and fetal injuries. RESULTS: When comparing pre- versus postimplementation surgical times, there was no significant difference in TOT (76.5 vs. 75.9 minutes, respectively; p = 0.42) or ITDT (9.8 vs. 8.8 minutes, respectively; p = 0.06) when the entire cohort was analyzed. Subgroup analysis of CD performed early versus late in an academic year among the pre- and postimplementation groups showed no significant difference in TOT (79.3 early vs. 73.8 minutes late; p = 0.10) or ITDT (10.8 early vs. 8.8 minutes late; p = 0.06) within the preimplementation group. In the postimplementation group, however, there was significant decrease in TOT (80.5 early vs. 71.3 minutes late; p = 0.02) and ITDT (10.6 early vs. 6.8 minutes late; p < 0.01). Secondary outcomes were similar for both groups. CONCLUSION: A standardized surgical technique combined with surgical experience can decrease TOT and ITDT in primary CD without increasing maternal morbidity.

Kyphosis and incident falls among community-dwelling older adults.

Hyperkyphosis commonly affects older persons and is associated with morbidity and mortality. Many have hypothesized that hyperkyphosis increases fall risk. Within this prospective study of older adults, kyphosis was significantly associated with incident falls over 1 year. Measures of hyperkyphosis could enhance falls risk assessments during primary care office visits. INTRODUCTION: To determine the association between four measures of kyphosis and incident and injurious falls in older persons. METHODS: Community-dwelling adults aged 65 and older (n = 72) residing in southern California were invited to participate in a prospective cohort study. Participants had kyphosis assessed four ways. Two standing measures included a flexicurve ruler placed against the back to derive a kyphotic index and the Debrunner kyphometer, a protractor used to measure the kyphotic angle in degrees. Two lying measures included the blocks method (number of 1.7 cm blocks needed to achieve a neutral head position while lying supine) and traditional Cobb angle calculation derived from DXA based lateral vertebral assessment. Baseline demographic, clinical, and other health information (including a timed up and go (TUG) test) were assessed at a clinic visit. Participants were followed monthly through email or postcard for 1 year, with falls outcomes confirmed through telephone interview. RESULTS: Mean age was 77.8 (± 7.1) among the 52 women and 20 men. Over 12 months, 64% of participants experienced at least one incident fall and 35% experienced an injurious fall. Each standard deviation increase in kyphosis resulted in more than doubling the adjusted odds of an incident fall, even after adjusting for TUG. Odds of injurious falls were less consistent across measures; after adjusting for TUG, only the blocks method was associated with injurious falls. CONCLUSIONS: Each kyphosis measure was independently associated with incident falls. Findings were inconsistent for injurious falls; the blocks measure suggested the strongest association. If these findings are replicated, the blocks measure could be incorporated into office visits as a quick and efficient tool to identify patients at increased fall risk.

Proteinase-activated receptor-2 blockade inhibits changes seen in a chronic murine asthma model.

BACKGROUND: Proteinase-Activated Receptor-2 (PAR2 ) is a G protein-coupled receptor activated by serine proteinases. We have shown that PAR2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness (AHR) in acute murine models. We hypothesized that functional inhibition of PAR2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. MATERIAL AND METHODS: We developed and used a 12 week model of cockroach extract (CE)-mediated AHR, airway inflammation and remodeling in BALB/c mice. RESULTS: Mice sensitized and challenged with CE for 12 weeks exhibit AHR, increased numbers of eosinophils in bronchoalveolar lavage (BAL) and increased collagen content in the lung tissue compared to saline controls. Administration of an anti-PAR2 antibody, SAM-11, after the initial development of airway inflammation significantly inhibited all these parameters. CONCLUSIONS: Our data demonstrate that PAR2 signaling plays a key role in CE-induced AHR and airway inflammation/remodeling in long term models of allergic airway inflammation. Targeting PAR2 activation may be a successful therapeutic strategy for allergic asthma.

Population-based study demonstrating an increase in colorectal cancer in young patients.

BACKGROUND: New Zealand has among the highest rates of colorectal cancer in the world and is an unscreened population. The aim of this study was to determine the trends in incidence and tumour location in the New Zealand population before the introduction of national colorectal cancer screening. METHODS: Data were obtained from the national cancer registry and linked to population data from 1995 to 2012. Incidence rates for colorectal cancer by sex, age (less than 50 years, 50-79 years, 80 years or more) and location (proximal colon, distal colon and rectum) were assessed by linear regression. RESULTS: Among patients aged under 50 years, the incidence of distal colonic cancer in men increased by 14 per cent per decade (incidence rate ratio (IRR 1·14), 95 per cent c.i. 1·00 to 1·30; P = 0·042); the incidence of rectal cancer in men increased by 18 per cent (IRR 1·18, 1·06 to 1·32; P = 0·002) and that in women by 13 per cent (IRR 1·13, 1·02 to 1·26; P = 0·023). In those aged 50-79 years, there was a reduction in incidence per decade of proximal, distal and rectal cancers in both sexes. In the group aged 80 years and over, proximal cancer incidence per decade increased by 19 per cent in women (IRR 1·19, 1·13 to 1·26; P < 0·001) and by 25 per cent in men (IRR 1·25, 1·18 to 1·32; P < 0·001); among women, the incidence of distal colonic cancer decreased by 8 per cent (IRR 0·92, 0·86 to 0·98); P = 0·012), as did that of rectal cancer (IRR 0·92, 0·86 to 0·97; P = 0·005). CONCLUSION: The increasing incidence of rectal cancer among younger patients needs to be considered when implementing screening strategies.

Hypersexuality in Psychiatric Conditions Observer-Rated Scale (HIPCORS): Evaluation of Reliability and Validity.

Hypersexual behavior is not uncommon in psychiatric presentations. Most available scales that measure hypersexual behavior are self-rated, often containing sexually explicit questions, unsuitable for use in mentally unwell people. Lack of a clinically suitable instrument may have resulted in underdetection and under-researching of hypersexuality in people with mental disorders, with potential to cause significant consequences for themselves and those around them, including family members, coclients, and clinicians. To address this need, we developed the Hypersexuality in Psychiatric Conditions Observer-Rated Scale (HIPCORS), a rater-rated, nonintrusive tool, designed for use in mentally unwell people. It has been shown to be a reliable and valid instrument.

Functional inhibition of PAR2 alleviates allergen-induced airway hyperresponsiveness and inflammation.

BACKGROUND: Proteinase-activated receptor 2 (PAR2 ) is a G protein-coupled receptor activated by trypsin-like serine proteinases. PAR2 activation has been associated with inflammation including allergic airway inflammation. We have also shown that PAR2 activation in the airways leads to allergic sensitization. The exact contribution of PAR2 in the development of eosinophilic inflammation and airway hyperresponsiveness (AHR) in sensitized individuals is not clear. OBJECTIVE: To investigate whether functional inhibition of PAR2 during allergen challenge of allergic mice would inhibit allergen-induced AHR and inflammation in mouse models of asthma. METHODS: Mice were sensitized and challenged with ovalbumin (OVA) or cockroach extract (CE). To investigate the role of PAR2 in the development of AHR and airway inflammation, we administered blocking anti-PAR2 antibodies, or a cell permeable peptide inhibitor of PAR2 signalling, pepducin, i.n. before allergen challenges and then assessed AHR and airway inflammation. RESULTS: Administration of anti-PAR2 antibodies significantly inhibited OVA- and CE-induced AHR and airway inflammation. In particular, two anti-PAR2 antibodies, the monoclonal SAM-11 and polyclonal B5, inhibited AHR, airway eosinophilia, the increase of cytokines in the lung tissue and antigen-specific T cell proliferation, but had no effect on antigen-specific IgG and IgE levels. Pepducin was also effective in inhibiting AHR and airway inflammation in an OVA model of allergic airway inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: Functional blockade of PAR2 in the airways during allergen challenge improves allergen-induced AHR and inflammation in mice. Therefore, topical PAR2 blockade in the airways, through anti-PAR2 antibodies or molecules that interrupt PAR2 signalling, has the potential to be used as a therapeutic option in allergic asthma.

A feasibility study of behavioural activation for depressive symptoms in adults with intellectual disabilities.

BACKGROUND: Important work has been carried out adapting cognitive behavioural therapy for people with intellectual disabilities. However, there is a lack of alternative psychological therapies available for people with intellectual disabilities and emotional difficulties. Behavioural activation for depression is less reliant on verbal communication and focuses on increasing purposeful activity and reducing avoidance. METHOD: This feasibility study involved the development and piloting of an adapted manual of behavioural activation for people with intellectual disabilities. The intervention consisted of 10-12 sessions and a key adaptation was that the therapist worked with the clients alongside a significant other in their life, either a paid carer or family member. Baseline, post-intervention (3 months after entering the study) and 6-month quantitative follow-up data were obtained. Primary outcome data were gathered, concerning depressive symptoms, participants' levels of activity and general well-being. RESULTS: Twenty-three adults with intellectual disabilities with symptoms of depression were recruited from specialist health services. In terms of acceptability, the behavioural activation intervention was well received and only two individuals dropped out, with a further two lost to follow-up. The main measures of depression appeared to be sensitive to change. Pre- to post-intervention data showed a significant reduction in self-report of depressive symptoms with a strong effect size (r = 0.78), that was maintained at follow-up (r = 0.86). Positive change was also obtained for informant reports of depressive symptoms from pre- to post-intervention, with a strong effect size (r = 0.7). Once again, this positive change was maintained at follow-up (r = 0.72). CONCLUSIONS: The study suggested that behavioural activation may be a feasible and worthwhile approach to tackling depression in people with intellectual disabilities. However, a randomised controlled trial would be required to establish its effectiveness, with more sensitive measurement of change in activity.

Objective comparison of a sit to stand test to the walk test for the identification of unilateral lameness caused by cranial cruciate ligament disease in dogs.

OBJECTIVE: The purpose of this study was to evaluate a sit to stand test with the walk test for the identification of unilateral cranial cruciate ligament rupture in dogs. MATERIALS AND METHODS: Peak vertical force and vertical impulse were measured on a pressure-sensitive walkway, during a sit to stand test and walk test, and in 10 dogs with unilateral cranial cruciate ligament rupture and 18 non-lame dogs. Data collected were used to calculate symmetry indices (SI) of ipsilateral and contralateral hindlimbs (HL), diagonal limb pairs (DLP) and ipsilateral limb pairs (ILP). RESULTS: The symmetry indices of peak vertical force of HL during the walk test and sit to stand test were 100% and 90% sensitive for discriminating lame and non-lame dogs respectively. The symmetry indices of vertical impulse of HLs during the walk test and sit to stand test were 100% and 50% sensitive for discriminating lame and non-lame dogs respectively. Analysis of ipsilateral and diagonal limb pairs did not improve the discrimination in either test. The time taken to collect data from the sit to stand test data was shorter than for the walk test. CLINICAL SIGNIFICANCE: Whilst the sit to stand test required a shorter time for collection of data than the walk test, it did not accurately identify all dogs with lameness associated with CCLR, and thus has relatively limited clinical utility in its tested form.

Proteinase-activated receptor-2 activation participates in allergic sensitization to house dust mite allergens in a murine model.

BACKGROUND: Many aeroallergens contain proteinase activity and are able to induce allergic sensitization when presented to mucosal surfaces. Some of these allergens activate proteinase-activated receptor-2 (PAR2 ). OBJECTIVE: To determine the role of PAR2 activation in a murine house dust mite (HDM) allergy model. METHODS: We sensitized and challenged PAR2 -deficient mice with HDM, and examined allergic outcomes compared to wild-type animals. To focus on the role of PAR2 in allergic sensitization, we administered a PAR2 blocking antibody to wild-type animals during the sensitization phase and examined the outcomes immediately after sensitization or following subsequent allergen challenge. RESULTS: We found PAR2 -deficient mice sensitized and challenged with HDM failed to develop airway inflammation, did not produce HDM-specific IgG1 and had less IL-4 mRNA in the lungs than wild-type animals. Prevention of PAR2 activation during sensitization in wild-type mice diminished the levels of Th2 mediators, including IL-4, IL-5 and IL-13, in the lungs. Blocking PAR2 during the sensitization phase also led to decreased manifestations of allergic disease, including airway hyperresponsiveness (AHR) and airway inflammation following subsequent allergen challenge. HDM-induced proliferation of splenocytes obtained from animals sensitized in the presence of PAR2 antibody was reduced relative to those that did not receive antibody. The effect of PAR2 blockade could be transferred to naïve mice through splenic CD4(+) T cells from sensitized mice. CONCLUSIONS AND CLINICAL RELEVANCE: PAR2 activation plays a key role during the sensitization phase of our HDM allergy model, leading to increased lung cytokine production and augmented lung reactivity. PAR2 activation is a common mechanism for sensitization to a wide variety of allergens and is therefore a potential pharmacological target to prevent allergy.

25 Tb/s transmission over 5,530 km using 16QAM at 5.2 b/s/Hz spectral efficiency.

We transmit 250x100G PDM RZ-16QAM channels with 5.2 b/s/Hz spectral efficiency over 5,530 km using single-stage C-band EDFAs equalized to 40 nm. We use single parity check coded modulation and all channels are decoded with no errors after iterative decoding between a MAP decoder and an LDPC based FEC algorithm. We also observe that the optimum power spectral density is nearly independent of SE, signal baud rate or modulation format in a dispersion uncompensated system.

A phase I/II study of decitabine in combination with panitumumab in patients with wild-type (wt) KRAS metastatic colorectal cancer.

PURPOSE: KRAS mutations are predictive of lack of response to monoclonal antibodies (mAb) against EGFR in metastatic colorectal cancer (mCRC). Most wild-type KRAS patients, however, are also resistant. Retrospective data suggest that EGFR silencing play a role in resistance to therapy. We conducted a study to evaluate the safety and efficacy of decitabine (a hypomethylating agent) in combination with panitumumab (mAb against EGFR) in mCRC patients. EXPERIMENTAL DESIGN: 20 patients with wild-type KRAS mCRC were included in this phase I/II study. Patients were treated with decitabine at 45 mg/m(2) IV over 2 h on day 1 and 15 and panitumumab 6 mg/kg IV over 1 h on day 8 and 22 every 28 days. Blood samples were collected at baseline, day 8, 15 and 22. Quantitative polymerase chain reaction was used to measure promoter-specific methylation in peripheral-blood cells (PBMCs). RESULTS: The most common adverse events were grade 1-2 (rash and hypomagnesemia); 3 (16 %) patients had grade III-IV neutropenia including one patient with neutropenic fever. Two of 20 patients (10 %) had a partial response. Both had previously received cetuximab. Ten patients had stable disease (3 of them longer than 16 weeks). Decreased methylation of the MAGE promoter was not evidenced in PBMCs. CONCLUSIONS: The combination of decitabine and panitumumab was well tolerated and showed activity in wild-type KRAS mCRC patients previously treated with cetuximab. Target modulation in surrogate tissues was not achieved and tumor biopsies were not available. Future studies evaluating hypomethylating agents in combination with EGFR mAb in patients with mCRC are warranted.

Multivariate analysis of potentially toxic metals in sediments of a tropical coastal lagoon.

Surface sediments collected from the Lagos Lagoon, Nigeria, and three adjoining rivers were analysed for their physicochemical properties and pseudo-total concentration of the potentially toxic metals (PTM) Cd, Cr, Cu, Pb and Zn. The concentration of the PTM varied seasonally and spatially. Odo-Iyaalaro was observed to be the most polluted river, with highest concentrations of 42.1 mg kg(-1), 102 mg kg(-1), 185 mg kg(-1), 154 mg kg(-1) and 1040 mg kg(-1) of Cd, Cr, Cu, Pb and Zn, respectively, while Ibeshe River was the least contaminated, apart from a site affected by Cu from the textile industry. Some of the sediments were found to be above the consensus-based probable effect concentrations and Dutch sediment guideline for metals. Overall metal concentrations were similar to those reported for other tropical lagoon and estuarine systems affected by anthropogenic inputs as a result of rapid urbanisation. Due to the large number of samples, principal component analysis was used to examine relationships within the data set. Generally, sediments collected during the dry season were observed to have higher concentration of PTM than those collected during the rainy season. This means that PTM could accumulate over a prolonged period and then be released relatively rapidly, on an annual basis, into tropical lagoon systems.

Using global feedback to induce learning of gist of abnormality in mammograms.

Extraction of global structural regularities provides general 'gist' of our everyday visual environment as it does the gist of abnormality for medical experts reviewing medical images. We investigated whether naïve observers could learn this gist of medical abnormality. Fifteen participants completed nine adaptive training sessions viewing four categories of unilateral mammograms: normal, obvious-abnormal, subtle-abnormal, and global signals of abnormality (mammograms with no visible lesions but from breasts contralateral to or years prior to the development of cancer) and receiving only categorical feedback. Performance was tested pre-training, post-training, and after a week's retention on 200 mammograms viewed for 500 ms without feedback. Performance measured as d' was modulated by mammogram category, with the highest performance for mammograms with visible lesions. Post-training, twelve observed showed increased d' for all mammogram categories but a subset of nine, labelled learners also showed a positive correlation of d' across training. Critically, learners learned to detect abnormality in mammograms with only the global signals, but improvements were poorly retained. A state-of-the-art breast cancer classifier detected mammograms with lesions but struggled to detect cancer in mammograms with the global signal of abnormality. The gist of abnormality can be learned through perceptual/incidental learning in mammograms both with and without visible lesions, subject to individual differences. Poor retention suggests perceptual tuning to gist needs maintenance, converging with findings that radiologists' gist performance correlates with the number of cases reviewed per year, not years of experience. The human visual system can tune itself to complex global signals not easily captured by current deep neural networks.

16QAM transmission with 5.2 bits/s/Hz spectral efficiency over transoceanic distance.

We transmit 160 x 100 G PDM RZ 16 QAM channels with 5.2 bits/s/Hz spectral efficiency over 6,860 km. There are more than 3 billion 16 QAM symbols, i.e., 12 billion bits, processed in total. Using coded modulation and iterative decoding between a MAP decoder and an LDPC based FEC all channels are decoded with no remaining errors.

The single nucleotide polymorphism CRTh2 rs533116 is associated with allergic asthma and increased expression of CRTh2.

BACKGROUND: CRTh2 (chemoattractant-receptor homologous molecule expressed on Th2 cells) is expressed by Th2 cells and other cells involved in allergic inflammation. Single nucleotide polymorphisms (SNPs) in CRTh2 (rs11571288, rs545659, rs634681) have been associated with various phenotypes of allergy in ethnically distinct populations. Here, we assessed the association between CRTh2 rs533116 and allergic asthma, expression of CRTh2 and Th2 cytokine production. METHODS: CRTh2 rs533116 was genotyped in an ethnically diverse population (n = 1282). The proportion of cells expressing CRTh2 was determined in peripheral blood from subjects with allergic airways disease and controls as well as with in vitro differentiated Th2 cells. Receptor function was assessed by stimulating Th2 cells with the CRTh2-specific agonist 13,14-dihydro-15-keto-PGD(2) (DK-PGD(2) ) and measuring IL-4 and IL-13 by intracellular staining and ELISA. RESULTS: CRTh2 rs533116 was associated with allergic asthma in White people (2.67 [1.09-6.55], P < 0.05), and expression of CRTh2 was higher in subjects with allergic airways disease compared to controls (P < 0.05). Among allergic individuals, the AA genotype was significantly associated with more eosinophils and higher expression of CRTh2 by both CD4(+) T cells and eosinophils (P < 0.05). In vitro, the AA genotype was associated with a higher proportion of CRTh2(+) cells during Th2 differentiation as well as more IL-4 and IL-13 expression following DK-PGD(2) stimulation (P < 0.05). CONCLUSIONS: These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRTh2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.

Hyperspectral cathodoluminescence imaging and analysis extending from ultraviolet to near infrared.

The measurement of near-infrared (NIR) cathodoluminescence (CL) with sufficient sensitivity to allow full spectral mapping has been investigated through the application of optimized grating spectrometers that allow the ultraviolet (UV), visible, and NIR CL spectra to be measured simultaneously. Two optical spectrometers have been integrated into an electron microprobe, allowing simultaneous collection of hyperspectral CL (UV-NIR), characteristic X-rays, and electron signals. Combined hyperspectral CL spectra collected from two natural apatite (Ca5[PO4]3[OH,F]) samples from Wilberforce (Ontario, Canada) and Durango (Mexico) were qualitatively analyzed to identify the emission centers and then deconvoluted pixel-by-pixel using least-squares fitting to produce a series of ion-resolved CL intensity maps. Preliminary investigation of apatite has shown strong NIR emissions associated primarily with the rare-earth element Nd. Details of growth and alteration were revealed in the NIR that were not discernable with electron-induced X-ray mapping. Intense emission centers from Nd3+ and Sm3+ were observed in the spectra from both apatites, along with minor emissions from other 3+ rare-earth elements. Quantitative electron probe microanalysis was performed on points within the mapped area of the Durango apatite to produce a calibration line relating cathodoluminescent intensity of the fitted peak centered at 1,073 nm (1.156 eV) to the Nd concentration.

Microbiome and Neurotrauma: Emerging Innovations.

The gut-brain axis plays an important role in bidirectional communication that exists and can be altered by injury. Neurotrauma provides acute alteration in the GI tract and alters autonomic function. In this focused review, we highlight what is known about GI disruption following neurotrauma. We then delve into how this affects recovery. Areas of innovation and emerging pre-clinical results are addressed. Finally, we address the link between neurotrauma induced GI dysfunction and progression to neurodegenerative disease states.

Applying Mendelian randomization to appraise causality in relationships between smoking, depression and inflammation.

Smoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, (an archetypal generalized inflammatory marker) and/or IL-6 activity, as a potential explanation for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated reciprocal relationships of lifetime smoking with depression (ORSmk-Dep = 2.01, 95% CI 1.71-2.37, p < 0.001; ORDep-Smk = 1.09, 95% CI 1.06-1.13, p < 0.001), CRP levels and IL-6 activity (ORSmk-CRP = 1.40, 95% CI 1.21-1.55, p < 0.001; ORCRP-Smk = 1.03, 95% CI 1.02-1.05, p < 0.001, ORIL-6/CRP-Smk = 1.06 (1.03-1.09), p < 0.001). These associations were also supported by the majority of the robust MR methods performed. We did not find evidence for a reciprocal relationship between CRP levels (using > 500 genetic instruments for CRP) and depression (ORCRP-Dep = 1.01, 95% CI 0.99-1.04; ORDep-CRP = 1.03, 95% CI 0.99-1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to measures of generalized inflammation, but we found evidence for an attenuation of the smoking-depression association in multivariable mendelian randomization when adjusting for IL-6 activity, suggesting that the IL-6 pathway may be at least in part responsible for the association of smoking and depression. Our study supports potential bidirectional causal associations between lifetime smoking and depression which may be at least in part explained by the IL-6 signalling pathway. The IL-6 pathway may represent a putative therapeutic target for smoking and to mitigate the effects of smoking on depression.

An emotional discrete controller PSO tuned and designed for a real industrial pumping system.

The application of automation techniques to water pump systems, combined with modern control techniques, has been increasing the hydraulic and energy efficiency of such systems. In this context, the objective of this work is to present an intelligent method of flow control based on Brain Emotional Learning Basic Intelligent Control (BELBIC), which will be applied to an experimental workbench of a pumping system, located in the Energy Efficiency and Energy Quality Laboratory (LEEQE) at Federal University of Pernambuco (UFPE). The parameters of this controller are optimized with a particle swarm optimization (PSO) technique with minimization of Integral Absolute Error (IAE). Initial tests were performed in a computational environment so that the system's performance could be pre-tested, thereby the dynamics of the system was modeled from real data generated in the process. The experimental results were obtained through the implementation of this control system in a programmable logic controller (PLC), which was the device responsible for all the automation of the workbench previously mentioned. The data of this workbench were collected using a supervisory system exclusively developed for this work. These data were then used to analyze the performance of the proposed control system, which demonstrated that its behavior was efficient.