Adaptive linear combination of heuristic orderings in constructing examination timetables

In this paper, we investigate adaptive linear combinations of graph coloring heuristics with a heuristic modifier to address the examination timetabling problem. We invoke a normalisation strategy for each parameter in order to generalise the specific problem data. Two graph coloring heuristics were used in this study (largest degree and saturation degree). A score for the difficulty of assigning each examination was obtained from an adaptive linear combination of these two heuristics and examinations in the list were ordered based on this value. The examinations with the score value representing the higher difficulty were chosen for scheduling based on two strategies. We tested for single and multiple heuristics with and without a heuristic modifier with different combinations of weight values for each parameter on the Toronto and ITC2007 benchmark data sets. We observed that the combination of multiple heuristics with a heuristic modifier offers an effective way to obtain good solution quality. Experimental results demonstrate that our approach delivers promising results. We conclude that this adaptive linear combination of heuristics is a highly effective method and simple to implement.

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100kb), rare copy number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1,564 cases and 1,748 controls all from Ireland, and further extended the analysis to include an additional 5,196 UK controls. We found association with duplications at chr20p12.2 (P=0.007) and evidence of replication in large independent European schizophrenia (P=0.052) and UK bipolar disorder case-control cohorts (P=0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11,707 cases and 10 carriers in 21,204 controls (meta-analysis CMH P value=2x10(-4) (odds ratio (OR)=11.3, 95% CI=3.7, ∞)). Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68Mb with similar breakpoints across samples. By haplotype analysis and sequencing we identified a tandem ∼149kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P=2.5x10(-21)), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity.

The influence of market deregulation on fast food consumption and body mass index:A cross-national time series analysis

Objective
To investigate the effect of fast food consumption on mean population body mass index (BMI) and explore the possible influence of market deregulation on fast food consumption and BMI.

Methods
The within-country association between fast food consumption and BMI in 25 high-income member countries of the Organisation for Economic Co-operation and Development between 1999 and 2008 was explored through multivariate panel regression models, after adjustment for per capita gross domestic product, urbanization, trade openness, lifestyle indicators and other covariates. The possible mediating effect of annual per capita intake of soft drinks, animal fats and total calories on the association between fast food consumption and BMI was also analysed. Two-stage least squares regression models were conducted, using economic freedom as an instrumental variable, to study the causal effect of fast food consumption on BMI.

Findings
After adjustment for covariates, each 1-unit increase in annual fast food transactions per capita was associated with an increase of 0.033 kg/m2 in age-standardized BMI (95% confidence interval, CI: 0.013–0.052). Only the intake of soft drinks – not animal fat or total calories – mediated the observed association (β: 0.030; 95% CI: 0.010–0.050). Economic freedom was an independent predictor of fast food consumption (β: 0.27; 95% CI: 0.16–0.37). When economic freedom was used as an instrumental variable, the association between fast food and BMI weakened but remained significant (β: 0.023; 95% CI: 0.001–0.045).

Conclusion
Fast food consumption is an independent predictor of mean BMI in high-income countries. Market deregulation policies may contribute to the obesity epidemic by facilitating the spread of fast food.

Symptoms and Endoscopic Features at Barrett's Esophagus Diagnosis: Implications for Neoplastic Progression Risk

OBJECTIVES: Risk stratification of Barrett's esophagus (BE) patients based on clinical and endoscopic features may help to optimize surveillance practice for esophageal adenocarcinoma (EAC) development. The aim of this study was to investigate patient symptoms and endoscopic features at index endoscopy and risk of neoplastic progression in a large population-based cohort of BE patients.

METHODS: A retrospective review of hospital records relating to incident BE diagnosis was conducted in a subset of patients with specialized intestinal metaplasia from the Northern Ireland BE register. Patients were matched to the Northern Ireland Cancer Registry to identify progressors to EAC or esophageal high-grade dysplasia (HGD). Cox proportional hazards models were applied to evaluate the association between endoscopic features, symptoms, and neoplastic progression risk.

RESULTS: During 27,997 person-years of follow-up, 128 of 3,148 BE patients progressed to develop HGD/EAC. Ulceration within the Barrett's segment, but not elsewhere in the esophagus, was associated with an increased risk of progression (hazard ratio (HR) 1.72; 95% confidence interval (CI): 1.08–2.76). Long-segment BE carried a significant sevenfold increased risk of progression compared with short-segment BE; none of the latter group developed EAC during the study period. Conversely, the absence of reflux symptoms was associated with an increased risk of cancer progression (HR 1.61; 95% CI: 1.05–2.46).

CONCLUSIONS: BE patients presenting with a long-segment BE or Barrett's ulcer have an increased risk of progressing to HGD/EAC and should be considered for more intense surveillance. The absence of reflux symptoms at BE diagnosis is not associated with a reduced risk of malignant progression, and may carry an increased risk of progression.

Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro and in Kenyan schoolchildren

SCOPE: This study explores the relationship between aflatoxin and the insulin-like growth factor (IGF) axis and its potential effect on child growth.

METHODS AND RESULTS: One hundred and ninety-nine Kenyan schoolchildren were studied for aflatoxin-albumin adduct (AF-alb), IGF1 and IGF-binding protein-3 (IGFBP3) levels using ELISA. AF-alb was inversely associated with IGF1 and IGFBP3 (p < 0.05). Both IGF1 and IGFBP3 were significantly associated with child height and weight (p < 0.01). Children in the highest tertile of AF-alb exposure (>198.5 pg/mg) were shorter than children in the lowest tertile (<74.5 pg/mg), after adjusting for confounders (p = 0.043). Path analysis suggested that IGF1 levels explained ∼16% of the impact of aflatoxin exposure on child height (p = 0.052). To further investigate this putative mechanistic pathway, HHL-16 liver cells (where HHL-16 is human hepatocyte line 16 cells) were treated with aflatoxin B1 (0.5, 5 and 20 μg/mL for 24-48 h). IGF1 and IGFBP3 gene expression measured by quantitative PCR and protein in culture media showed a significant down-regulation of IGF genes and reduced IGF protein levels.

CONCLUSION: Aflatoxin treatment resulted in a significant decrease in IGF gene and protein expression in vitro. IGF protein levels were also lower in children with the highest levels of AFB-alb adducts. The data suggest that aflatoxin-induced changes in IGF protein levels could contribute to growth impairment where aflatoxin exposure is high.

Effect of shotpeening on sliding wear and tensile behavior of titanium implant alloys

Titanium has good biocompatibility and so its alloys are used as implant materials, but they suffer from having poor wear resistance. This research aims to improve the wear resistance and the tensile strength of titanium alloys potentially for implant applications. Titanium alloys Ti–6Al–4V and Ti–6Al–7Nb were subjected to shotpeening process to study the wear and tensile behavior. An improvement in the wear resistance has been achieved due to surface hardening of these alloys by the process of shotpeening. Surface microhardness of shotpeened Ti–6Al–4V and Ti–6Al–7Nb alloys has increased by 113 and 58 HV(0.5), respectively. After shotpeening, ultimate tensile strength of Ti–6Al–4V increased from 1000 MPa to 1150 MPa, higher than improvement obtained for heat treated titanium specimens. The results confirm that shotpeening pre-treatment improved tensile and sliding wear behavior of Ti–6Al–4V and Ti–6Al–7Nb alloys. In addition, shotpeening increased surface roughness.

Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: A prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial

Background: Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. 

Methods: In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. 

Findings: Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with placebo was seen in both docetaxel subgroups for most main secondary efficacy endpoints; risk for time to time to first symptomatic skeletal event was reduced with radium-223 versus placebo in patients with previous docetaxel use, but the difference was not significant in those with no previous docetaxel use. 322 (62%) of 518 patients previously treated with docetaxel had grade 3-4 adverse events, compared with 205 (54%) of 383 patients without docetaxel. Patients who had previously been treated with docetaxel had a higher incidence of grade 3-4 thrombocytopenia with radium-223 than with placebo (31 [9%] of 347 patients vs five [3%] of 171 patients), whereas the incidence was similar between treatment groups among patients with no previous docetaxel use (seven [3%] of 253 patients vs one [1%] of 130 patients). The incidences of grade 3-4 anaemia and neutropenia were similar between the radium-223 and placebo groups within both docetaxel subgroups. 

Interpretation: Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use. 

Funding: Algeta ASA and Bayer HealthCare Pharmaceuticals.

Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells

BACKGROUND AND PURPOSE: NF-κB-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3 ) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction.

EXPERIMENTAL APPROACH: Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA3 , stimulated with Pseudomonas aeruginosa LPS; IL-6 and IL-8 release, A20, NF-κB and IκBα expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA.

KEY RESULTS: Cells pre-incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IκBα degradation and reduced NF-κB (p65) expression. Furthermore, the anti-inflammatory action of GA3 was abolished in A20-silenced cells.

CONCLUSIONS AND IMPLICATIONS: We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-κB and IκBα. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction.

Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial

BACKGROUND: Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases.

METHODS: In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751.

FINDINGS: Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15·6 months [95% CI 13·5-18·0] vs 9·8 months [7·3-23·7]; hazard ratio [HR]=0·66, 95% CI 0·52-0·83; p=0·00037). The risks of external beam radiation therapy for bone pain (HR 0·67, 95% CI 0·53-0·85) and spinal cord compression (HR=0·52, 95% CI 0·29-0·93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0·62, 95% CI 0·35-1·09), or the need for tumour-related orthopaedic surgical intervention (HR 0·72, 95% CI 0·28-1·82).

INTERPRETATION: Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.

FUNDING: Algeta and Bayer HealthCare Pharmaceuticals.

Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials

BACKGROUND: The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.

METHODS: We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptor-positive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen first-event rate ratios (RRs).

FINDINGS: In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0·64, 95% CI 0·52-0·78) and 2-4 (RR 0·80, 0·68-0·93), and non-significantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12·1% vs 14·2%; RR 0·85, 0·75-0·96; 2p=0·009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0·74, 0·62-0·89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0·90, 0·81-0·99; 2p=0·045), though the breast cancer mortality reduction was not significant (RR 0·89, 0·78-1·03; 2p=0·11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 2-4 (RR 0·56, 0·46-0·67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8·7% vs 10·1%; 2p=0·015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments differed (RR 0·70, 0·64-0·77), but not significantly thereafter (RR 0·93, 0·86-1·01; 2p=0·08). Breast cancer mortality was reduced both while treatments differed (RR 0·79, 0·67-0·92), and subsequently (RR 0·89, 0·81-0·99), and for all periods combined (RR 0·86, 0·80-0·94; 2p=0·0005). All-cause mortality was also reduced (RR 0·88, 0·82-0·94; 2p=0·0003). RRs differed little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0·4% vs 1·2%; RR 0·33, 0·21-0·51) but more bone fractures (5-year risk 8·2% vs 5·5%; RR 1·42, 1·28-1·57); non-breast-cancer mortality was similar.

INTERPRETATION: Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments differ, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.

FUNDING: Cancer Research UK, Medical Research Council.

A large scale model experimental study of a tidal turbine in uniform steady flow

An experimental study measuring the performance and wake characteristics of a 1:10th scale horizontal axis turbine in steady uniform flow conditions is presented in this paper.
Large scale towing tests conducted in a lake were devised to model the performance of the tidal turbine and measure the wake produced. As a simplification of the marine environment, towing the turbine in a lake provides approximately steady, uniform inflow conditions. A 16m long x 6m wide catamaran was constructed for the test programme. This doubled as a towing rig and flow measurement platform, providing a fixed frame of reference for measurements in the wake of a horizontal axis tidal turbine. Velocity mapping was conducted using Acoustic Doppler Velocimeters.
The results indicate varying the inflow speed yielded little difference in the efficiency of the turbine or the wake velocity deficit characteristics provided the same tip speed ratio is used. Increasing the inflow velocity from 0.9 m/s to 1.2 m/s influenced the turbulent wake characteristics more markedly. The results also demonstrate that the flow field in the wake of a horizontal axis tidal turbine is strongly affected by the turbine support structure

Corneal biomechanics, refractive error, and axial length in Chinese primary school children.

PURPOSE: Low corneal hysteresis is associated with longer axial length in Chinese secondary school children. The authors sought to explore this association in primary school children. METHODS: LogMAR presenting visual acuity, cycloplegic refractive error, ocular biometry, central corneal thickness (CCT), and corneal hysteresis (CH) was assessed for children in grades 1 to 3 at an academically competitive urban school in Shantou, China. RESULTS: Among 872 eligible children (mean age, 8.6 ± 2.1 years), 651 (74.7%) completed the examination. Among 1299 examined eyes, 111 (8.5%) had uncorrected vision ≤6/12. Mean spherical equivalent refractive error for all eyes was +0.26 ± 1.41 D, and axial length (AL) was 22.7 ± 0.90 mm. CH for the lowest (mean AL, 21.7 ± 0.39 mm), two middle (mean AL, 22.4 ± 0.15 and 22.9 ± 0.15 mm), and highest quartiles (mean AL, 23.7 ± 0.74 mm) of AL were 10.6 ± 2.1 mm Hg, 10.4 ± 2.1 mm Hg, 10.3 ± 2.3 mm Hg, and 10.2 ± 2.3 mm Hg respectively (age- and gender-adjusted Pearson's correlation coefficient r = -0.052; P = 0.001). In generalized estimating equation models adjusting for age, gender, and CCT, lower CH was significantly associated with longer AL (P < 0.001) and more myopic refractive error (P = 0.001). CONCLUSIONS: CH measurement is practical in young children because this is when myopia undergoes its most rapid progression. Prospective follow-up of this cohort at high risk for myopia is under way to determine whether low CH is predictive, or a consequence, of long AL.

Real-time estimation of battery internal temperature based on a simplified thermoelectric model

Li-ion batteries have been widely used in the EVs, and the battery thermal management is a key but challenging part of the battery management system. For EV batteries, only the battery surface temperature can be measured in real-time. However, it is the battery internal temperature that directly affects the battery performance, and large temperature difference may exist between surface and internal temperatures, especially in high power demand applications. In this paper, an online battery internal temperature estimation method is proposed based on a novel simplified thermoelectric model. The battery thermal behaviour is first described by a simplified thermal model, and battery electrical behaviour by an electric model. Then, these two models are interrelated to capture the interactions between battery thermal and electrical behaviours, thus offer a comprehensive description of the battery behaviour that is useful for battery management. Finally, based on the developed model, the battery internal temperature is estimated using an extended Kalman filter. The experimental results confirm the efficacy of the proposed method, and it can be used for online internal temperature estimation which is a key indicator for better real-time battery thermal management.

Implementation of a new atomic basis for the He i equilibrium line ratio technique for electron temperature and density diagnostic in the SOL for H-mode plasmas in DIII-D

Evaluating the ratio of selected helium lines allows for measurement of electron densities and temperatures. This technique is applied for L-mode plasmas at TEXTOR (O. Schmitz et al., Plasma Phys. Control. Fusion 50 (2008) 115004). We report our first efforts to extend it to H-mode plasma diagnostics in DIII-D. This technique depends on the accuracy of the atomic data used in the collisional radiative model (CRM). We present predictions for the electron temperatures and densities by using recently calculated R-Matrix With Pseudostates (RMPS) and Convergent Close-Coupling (CCC) electron-impact excitation and ionization data. We include contributions from higher Rydberg states by means of the projection matrix. These effects become significant for high electron density conditions, which are typical in H-mode. We apply a non-equilibrium model for the time propagation of the ionization balance to predict line emission profiles from experimental H-mode data from DIII-D. © 2010 Elsevier B.V. All rights reserved.

Violência e Envelhecimento: Compreender para Intervir

A violência é inquestionavelmente um problema que ensombra a atualidade nacional e internacional, estando presente nos mais diversos contextos sociais, inclusive na família. Não sendo um fenómeno novo, só recentemente a violência foi encarada como um problema de saúde pública, talvez pela preocupação crescente de várias organizações, pelo facto de ser reconhecida pela sociedade como um problema e pelas consequências tanto para as vítimas como para a sociedade.Por outro lado, as atuais características demográficas de Portugal determinam que a violência sobre os idosos se assuma como um problema complexo, que reclama políticas públicas e planos de intervenção efetivos. Tratando-se de um problema desta natureza, além das intervenções individuais, é indispensável a intervenção das instituições, numa perspectiva multidisciplinar e em rede. De modo a contribuir para que as respostas fossem mais efetivas foi criada a RIIDE (Rede de Intervenção Integrada do Distrito de Évora).