Suchergebnisse

Nonadherence to antiretroviral therapy (ART) may cause virologic failure and disease progression has been associated with switch of viral coreceptor usage from CCR5 to CXCR4. We aimed to assess the association between patient‐reported non‐adherence and HIV tropism. This is a cross‐sectional analysis. HIV‐tropism was performed within routine clinical practice either at start of ART or at virological failure. Adherence questionnaire includes: how many times ART has been taken during the last month, missed doses in the last week, timing deviation, refill interruption, drug holidays. Demographics, epidemiological data, HIV and ART history, CD4 and HIVRNA were collected. To assess co‐receptor tropism, env V3 genotyping from viremic plasma HIVRNA was performed. For the analysis, dual/mixed viruses were considered as X4. We included 102 individuals: 76% males; median age 42 y (IQR, 37–46); transmission was heterosexual 37%, homosexual 31%, intravenous drug use 29%. Median nadir of CD4 154/mmc (IQR, 53–274), median zenith of HIVRNA 5.26 (4.72–5.70), 46% had AIDS. 124 tropism tests were: 78% R5, 17% X4, 5% dual/mixed. In cases with previous ART, mono/dual ART was found in 26%, median number of regimens was 5 (IQR, 2–10), median time on triple‐ART was 54 months (IQR, 0–123) with median time of HIVRNA <50 c/ml of 16 months (IQR, 6.5–34.9). At HIV‐tropism, median CD4 and HIV RNA were 321/mmc (IQR, 210–436) and 2.65 (IQR, 2.65–4.91), respectively. Median time between adherence questionnaire and HIV‐tropism was 68 days (IQR, 23–116). At adherence questionnaire, median percentage of ART taken during the last month was 100% (IQR, 90–100), 39% reported missed doses in the last week, 40% timing deviation, 7% refill interruption, 17% drug holidays. At univariate analysis, no statistically significant association between non‐adherence and dual/mixed‐X4 viruses was found (p>0.1). Also gender, age, HIV transmission, AIDS, CD4 nadir, HIVRNA zenith, mono/dual ART, and number of ART regimens were not associated with type of tropism. Only longer time with undetectable HIVRNA before tropism test showed a lower probability of dual/mixed‐X4 viruses (OR for each month 0.95; 95% CI 0.90–1.00; p=0.06). No significant association between adherence and HIV‐tropism was found in this preliminary analysis. It is possible that patient self‐reported adherence is not able to capture nonadherence behaviors that underlie more pronounced viral replication which may be necessary for tropism switch.

HIV‐1‐infected patients are thought to be at higher risk of cardiovascular events. Measures of arterial stiffness are independently associated with cardiovascular risk [1]. The aim of our study was to determine if higher Framingham risk is associated with higher carotid femoral pulse wave velocity (cfPWV) in HIV‐infected volunteers (HIV cohort) and to establish whether there is a difference in cfPWV between the HIV cohort and age‐ and gender‐matched controls. We recruited 47 males (HIV cohort) on antiretroviral treatment, from a UK HIV clinic between October 2010 and March 2012 (31 low Framingham risk <10% and 16 high risk >20%). This group was matched with 46 healthy subjects from a contemporaneous study performed by our group. The inclusion criteria were: age 35–75 years with Framingham risk >20% or <10%, on antiretroviral treatment with undetectable viral load, no previous coronary heart disease, stroke or insulin therapy. Subjects underwent cfPWV measurement using Complior® (Artech, France). Student's t‐test was used to evaluate differences between high‐ and low‐risk groups and also between cases and controls. The mean age of the HIV cohort was 49.43±9.35 years (mean±SD) and in the control group 52.20±8.80 years (p=0.15). Mean duration of HIV infection was 13.83±7.25 years, mean CD4 count was 728.81±312.62×106/L and all viral loads were undetectable. In the HIV cohort, cfPWV was 8.39±1.09 m/s in the low‐risk group and 10.43±2.93 m/s in the high‐risk group (p=0.02). Multivariate analysis with cfPWV as dependent variable, and age, systolic blood pressure, cholesterol, smoking history, duration of HIV infection and antiretroviral therapy, zenith viral loads and nadir CD4 counts as independent variables was performed in the high‐ and low‐risk groups. This showed age alone to be a significant predictive factor (p=0.002). With Framingham risk as dependent variable and using the above factors as independent variables, no HIV‐related factors were significant predictors. The overall mean cfPWV for the HIV cohort (n=47) was 9.09±2.13 m/s compared to 11.95±2.37 m/s in the control group (n=46)(p<0.01). HIV infection does not contribute to increased cardiovascular risk as assessed by Framingham risk score or carotid‐femoral pulse wave velocity. This may be due to good control of traditional cardiovascular risk factors and a healthy lifestyle in this cohort.

Purpose of the studyConsidering costs of antiretrovirals (ARVs) for HIV patients is increasingly needed. A simple and comprehensive tool weighing comorbidities and ARV‐related toxicities could be useful to judge the appropriateness of use of more expensive drugs. We conceived a MultiFactorial Risk Score (MFRS) to evaluate the appropriateness of ARVs prescription relative to their costs.MethodsHIV patients were consecutively enrolled in 2010‐2011. We considered socio‐demographic characteristics, HIV history, cardiovascular risk factors, low energy fractures, bone density. Psychological factors were assessed by BDI, DS14 and TAS‐20. The MFRS was calculated as the sum of the following: age (<30y 1 point; 1 point increase every 5y, 10 for≥70); AIDS diagnosis (5); CD4 nadir (5 if <100; 1 point less every 100 CD4 increase); ART line (0 first, up to 5 for≥6 lines); lipodistrophy (5); HCV coinfection (7); education (1 degree, 2 secondary, 3 primary); alcohol (3) and drug abuse (5); working activity (3 if unemployed); hypertension (3); cholesterol≥200 mg/dl (3); diabetes (3); Framingham score (7 if>7%); creatinine (0 if <1 mg/dl, 1 if<1.2; 2 if<1.5>1.2, 5 if<2> 1.5, 7 if≥2); bone fractures (7); bone status at DEXA (0 normal, 3 osteopenic, 5 osteoporotic); cancer (5); depression (3 if BDI>17); other psychiatric illness (5). Annual costs of individual ART regimens were calculated. MFRS was correlated in univariate and multivariate models with all variables. All statistical analyses were carried out using Stata 10.1.Summary of resultsWe enrolled 241 HIV patients, 74.3% males, aged 44.5±9.9y; 19 patients (7.8%) were untreated, 74.8% of treated had undetectable HIV RNA. Mean Nadir CD4 counts were 218±168, 38.5% of patients had an AIDS diagnosis. Mean individual ARV annual cost was 10,976±5,360. Mean MFRS was 28.5±13.9 (4–64). MFRS was significantly higher (p<0.001) in patients with older age, longer duration of HIV infection, lower CD4 nadirs, AIDS diagnosis, lipodistrophy, HCV, smoking, lower education, alcohol/drug abuse, hypertension, carotid plaques, higher Framingham score, diabetes, bone fractures or disorders, depression, alexithymia, and higher ARV costs. In multivariate models, ARV costs were significantly higher in patients with older age, previous AIDS diagnosis, lower CD4 nadir and higher MFRS.ConclusionsMFRS may be a simple and reliable tool to match patients' complexity and ARV costs, deserving further validation on larger samples.

We present baseline data (follow up due w24–48) from MSM Neurocog ‐ prospective cohort study describing neurocognitive (NC) function in men who have sex with men (MSM) 18–50y.ObjectivesDescribe prevalence of positive screen for NC impairment (NCI) using Brief Neurocognitive Screen (BNCS); follow NC function over time.Data collectedDemographics, medical history, current/nadir CD4, current/peak viral load, antiretroviral (ART) use, recreational drug/tobacco/alcohol use. Subjects screen for depression (PHQ9), anxiety (GAD7), subjective memory problems (Everyday Memory Questionnaire [EMQ]). PHQ9, GAD7, EMQ, IHDS have fixed numerical cut‐offs. BNCS interpreted by calculating composite z score for each subject based on distance from mean in three component tests. Comparing to population norms may overcall NCI. We used participants to construct HIV+ normal ranges after exclusion of anxiety/depression, comparing individuals to this range. 235 screened (205 HIV+, 30 HIV−). In HIV+group 59 (28.8%) excluded as GAD7>10, PHQ9>15 or both (2 no data). 144 HIV+ analysed. 124 (86.1%) had normal z score (within 1 SD of mean). 20 (13.9%) had abnormal z: 7 (35%) asymptomatic, 13 (65%) symptomatic (analysed together). Not enough cognitive domains assessed by BNCS to formally diagnose HIV‐related NCI. BNCS abnormals less likely to be educated at university level/beyond (40% vs. 62.1%, p=0.02) or in skilled work (45% vs. 81.5%, p<0.0001). Current/ex‐recreational drug use similar (~80%); no significant association to score. All patients with abnormal z receiving ART; individual agents not associated with abnormality. IHDS correlated with abnormal BNCS (60% abnormal z had abnormal IHDS vs. 15.3% of normal, p<0.0001). No CD4 association with abnormal z (median nadir 244 in both, p=0.38). Of note, group median age was statistically different but actual difference small (normal 41y vs. abnormal 44y p<0.0001; HIV− 33y). BNCS outcome is age‐related but stratification of results would make abnormal numbers too low for interpretation. In any case, no NCI seen following referral. No‐one referred for formal psychometric testing after screening shown to have NCI. We show high anxiety, depression and current/previous recreational drug use in HIV+MSM 18–50y. Subjective concerns do not translate into confirmed NCI. Patient pathways should include screening for anxiety/depression and substance use, but in this young MSM group concerns regarding memory/functional impairment seem unfounded.

Patients' acceptability of HAART is a subjective variable that may deeply influence therapeutic outcome. The feeling of the patient may alter adherence and lead to virologic failure. Acceptability may depend on various variables often difficulty evaluated by the care‐giver. In a clinical setting the evaluation of acceptability is difficult, too, as patients may feel a judgement and be less sincere. Aim of this study was to asses adherence and acceptability of HAART. To limit reporting biases, the study was performed in five different non‐clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi‐structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. In these notes we focus on this last patient‐oriented outcome. Most of the subjects were males (66%) with a mean age of 46 years, with higher education level (72%) and a long history of HIV infection (mean 13.6 years). Consequently only 17% of patients were on a first‐line regimen. Patients reporting a high or very high acceptability of HAART were 60% compared to a 31% reporting a fair grade of satisfaction and a 9% indicating low or null acceptability. However the type of the regimen significantly influenced patients' acceptability. Single‐tablet regimens (STRs), OD regimens with more than one tablet/day or BID regimens were scored as highly acceptable in 84%; 61%; and 53% of cases, respectively (P < 0.0001) (Figure). Statistical significance was retained when the dosing schedule was entered in a multivariate logistic model. When the analysis was restricted to experienced patients 62% of them were currently on a regimen based on a reduced number of pills compared to the previous one. Patients scored the previous regimen as more difficult to comply with in 72% of cases; as difficult in 22% and less difficult in 6%. The eventuality of AEs (40%); respect of timing of pill intake (39%) and number of pills (27%) were the major reasons of patients' low acceptability of HAART. High acceptability is one of the winning characteristics of a regimen, favoring long‐term adherence, durability and efficacy. Although highly subjective, acceptability may be positively influenced by characteristics of the HAART regimen such as simplicity. According to our results, STRs show a higher acceptability compared to more complex regimens.Patient reported acceptability for thier current HAART regimen.image

The French RACING cohort study is a 24‐month, observational, longitudinal, prospective, multicenter study on HIV‐1 infected patients being treated with an antiretroviral combination therapy containing raltegravir. The objectives of this study are to describe the viro‐immunological course, characterize and document adverse events (AEs), describe patient adherence at M6 (month 6) and examine clinical‐biological data for patients undergoing ARV therapy including raltegravir at M12 (month 12). Demographic, viro‐immunological, safety and clinical‐biological data were collected at M6 and M12 and self‐reported patient adherence to treatment regimen at M6. Data from 478 of 482 patients were available at M12. The median age was 45.9 years (IQR: 40.0–52.2), 64.1% were male and the median duration of infection was 13.2 years (IQR: 5.5–21). At the baseline, 64.1% of patients had a cardiovascular risk factor or a history of cardiovascular events and 65.2% had received concomitant treatment (psychotropic drugs: 33.5%, lipid‐lowering drugs: 30% and antihypertensive agents: 24.8%). The virological response, viral load and CD4 cell count are shown in Table 1 (based on data available at M6 and M12). Of the 134 reported and treatment‐related AEs, the symptoms most frequently described (>5%) were myalgia (6.7%) and nausea (5.2%). A total of 34 serious adverse events were reported, of which 5 were possibly or probably related to raltegravir. Self‐reported patient adherence at M6 is described as follows: 'high' for 56% of patients, 'average' for 36% of patients and 'low' for 8% of patients (205 questionnaires). To conclude, in a real‐life setting concerning patients with a strong proportion of co‐morbidity and variation in adherence, the efficacy and safety data observed after 12 months are comparable to the data observed (not shown) in clinical studies.

Viro‐immunological data












Naïve No previous treatment n=65
Switch Previous treatment with a viral load<50 copies/mL n=258
Failure Previous treatment with a viral load>50 copies/Ml n=151




Median Viral Load (copies/mL) at baseline
64,513
–
1,891


Median CD4 (cells/mm3) at baseline
308
556
365



M6
M12
M6
M12
M6
M12


Virological Response% (HIV‐RNA<50 copies/mL)
77% n=56
87% n=62
92% n=191
94% n=211
70% n=112
73% n=125


Immunological Response Median CD4 count (cells/mm3)
461 n=58
514 n=63
592 n=205
591 n=209
451 n=124
490 n=126

BackgroundIn virologically suppressed patients, simplifying to darunavir/ ritonavir (DRV/r) monotherapy maintains HIV RNA suppression and could lower treatment costs. Monotherapy is mentioned as an alternative treatment option in the Greek therapeutic guidelines (posted in the Greek Health Authority website), even though it is not included in the label of darunavir or any other PI.MethodsIn the MONET trial 256 patients with HIV RNA<50 copies/mL and no history of virological failure on HAART were switched to DRV/r 800/100 mg once daily, either as monotherapy (n=127) or with 2NRTI (n=129). The three‐year analysis of the MONET trial was used to calculate the overall nationwide cost of switching to DRV/r monotherapy in Greek patients. We used a 'switch included' analysis at Week 144 to account for additional antiretrovirals taken after initial treatment failure. Published Greek hospital prices of antiretrovirals were used in this analysis. Data from a local expert panel were used to estimate the number of patients currently receiving NNRTI versus PI‐based treatment in Greece, and the number of patients eligible for DRV/r monotherapy.ResultsIn the ITT switch included analysis, HIV RNA<50 copies/mL by Week 144 was 86.1% versus 84.3% in the DRV/r monotherapy and control arms. No patients developed resistance to DRV as measured by virtual phenotype. Before the trial, the mean annual cost of antiretrovirals was €5,625 for patients on NNRTI‐based HAART, and €6,935 for patients on PI‐based HAART. The mean per‐patient cost in the monotherapy arm was €4,514 in the MONET trial (including the cost of intensification with NRTIs where needed): this annual cost of antiretrovirals was €1,111 lower (20%) than NNRTI‐based treatment, and €2,421 (35%) lower than PI‐based treatment taken before the trial, respectively. According to the local expert panel feedback 5,230 people are treated with antiretrovirals in Greece (40% NNRTI‐based, 60% PI‐based) and 20% of patients (n=1,046) are eligible for PI monotherapy. Based on the MONET results, a switch to DRV/r monotherapy in 20% of patients could reduce the three‐year cost of antiretroviral treatment for these patients, from €20.11 million to €14.26 million.ConclusionsBased on the MONET trial results, if the 1,046 eligible patients were to switch to PI monotherapy the lower cost of DRV/r monotherapy versus triple therapy in Greece would allow a potential saving of up to €5.85 million over three years.

Purpose of the studyDual therapy with lamivudine plus a PI boosted with ritonavir (PI/r) could be an alternative to standard triple therapy or PI/r monotherapy as a simplification strategy in patients with toxicity to nucleoside analogues (NA).MethodsRetrospective cohort study of 44 HIV‐infected patients on suppressive HAART, with no chronic HBV, who simplified to this dual therapy since 2008. Virological and immunological outcome, lipids and renal changes were evaluated.Summary of resultsMean age was 50 years (38‐70), 66% were male, and the median time of HIV infection was 18.6 years. The median nadir CD4+ count was 150 cells/ml (2–407). At inclusion, patients were receiving therapy with lamivudine plus atazanavir/r in 5 cases, lopinavir/r in 12, and darunavir/r in 27, and they had an HIV RNA level<50 copies/ml for a median time of 794 days (129–2344, 90% >6 months). The NA discontinued was tenofovir (27), didanosine (12), AZT (3), and d4T (2). The reasons for changing were toxicity in 76% of cases, especially renal impairment. They had received a mean of 8 regimens before (2–20), and 55% were in CDC‐stage C. In 11 cases, history of resistance was available (to NA in 7 cases, including the 210W mutation in four). The mutations 184V was not observed, but four patients (9%) had a previous failure to therapy including 3tC. Mutations in the protease gene were observed in 8 patients (2 to 7 mutations, the most frequent 77I and 93L), without resistance to the current PI/r. During 62.8 patient‐years of follow‐up (median, 802 days), only 2 patients failed (4.5%), due to incomplete adherence, at 27 and 141 days. Of note, these two patients had no previous failed with 3tC or PI. Overall, CD4+ count increased for 55 cells/ml. No new adverse events were observed, but total cholesterol (from 180 to 246 mg/dl, p=0.007) and triglycerides (from 166 to 195, p=0.01) increased during the first 24 weeks with improvement at 48 weeks. On the other hand, estimated glomerular filtration rate improved during follow up (from 74.2 ml/min to 83.08 ml/min after 48 weeks, p=0.1).ConclusionsDual therapy with lamivudine plus a boosted PI is safe and effective as simplification strategy in patients with toxicity to NA. This combination could be an alternative to mono or triple therapy in hard to treat patients, although an initial increase in lipid parameters could be observed.

PurposeDue to the relative low age of HIV‐infected patients, Framingham risk score (FRS) usually estimates a low CVD risk. Lifetime risk estimations use the risk of developing CVD over the course of an individual's remaining lifetime and may be useful in communicating the risk of CVD to young patients. Our aim is to estimate the lifetime risk of CVD in a representative sample of HIV patients under antiretroviral therapy in Spain.MethodsCross‐sectional analysis in 10 HIV units across Spain, including information on demographics, HIV disease status, treatment history and cardiovascular risk factors of subject under ART. Lifetime CVD risk was calculated with the method of Berry et al, which classifies the lifetime risk in five mutually exclusive categories: 1. All risk factors are optimal; 2. At least one risk factor is not optimal; 3. At least one risk factor is elevated; 4. One major risk factor is present; and 5. Two or more major risk factors are present. Risk factors included are cholesterol level, blood pressure, diabetes and tobacco smoking. We grouped these five categories in two major groups, low‐risk (groups 1+2+3) and high‐risk category (groups 4+5). We calculated the prevalence of having a high lifetime risk, and its crude and aOR (adjusted by age, sex, place of origin, education level, transmission category, time since HIV diagnosis, CDC stage, current and nadir CD4 count, HCV coinfection, time on current and total ART, being on the first ART regimen, and PI vs. NNRTI regimen).ResultsWe included 839 subjects free of previous CVD disease: 72% men, median age 45.6y, median CD4 count 598 cells, median time since HIV diagnosis 11y, median time on ART 6.3y, 87% had undetectable VL. Estimated 10‐year CVD risk was low (<5%) in 78% of the patients, and intermediate (5–10%) in 20%. Lifetime risk estimation shows a high risk profile for 71.4% of the population studied (≥1 major risk factors). Factors significantly and independently associated with an increased lifetime risk were older age, non‐Spanish origin and longer time on ART. Adjusted OR for patients on ART longer than 10 years (vs<5 years) was 2.2 [95% CI 1.13–4.34]. No relationship was found with current or nadir CD4 lymphocyte counts, CDC stage C, HCV confection or type of ART.ConclusionsThere are significant disparities between the low 10y CVD risk estimated with FRS and the elevated lifetime risk in HIV patients on ART. Prolonged ART is associated with an increased CVD lifetime risk.

ABSTRACT
The history of accounting for private railway companies in Germany shows that these companies played a major role in the diffusion of historical cost accounting principles and gave birth, together with big other joint stock companies, to the "dynamic" or second stage of capitalist accounting, at least in continental Europe.
If the representatives of such railway companies did not develop new concepts of accounting, notably as concerned depreciation, they had, by 1875–1879, elaborated a new theory of accounting (historical cost or dynamic theory).This theory had a profound impact at least on the German theorists of the late 19th century and early 20th centuries such as Simon, Rieger and Schmalenbach.
This new theory was needed to justify a new law favoring shareholders in a hurry for returns on their investments rather than company creditors. It also defeated the ideology of public finance and patrimonial (or static) theories of accounting. This new theory preceded the law which promulgated the new approach and clearly defended the private interests of shareholders as opposed to those of the public in the strict sense. It appears to contradict Watts and Zimmermann's basic hypothesis of the «theory of market excuses». Agency theory seemingly does not to apply either, for the new theory was proposed by managers allied to shareholders, specifically those «hurried shareholders", against creditors. This is why a kind of «theory of alliance» appears to be more consistent with these developments. The main reasons for developing the new accounting theory were linked to the issue of dividends. It was necessary to find an accounting approach which would allow the distribution of dividends at the very beginning of an investment cycle. It was also intended to find an accounting approach which would ensure that profits were distributed as evenly as possible throughout the entire investment cycle and among the different shareholders who had financed the investment.
Hence, the second stage of the capitalist accounting development was not connected to measure of performance or information problems (monitoring and bonding) but seems to have been caused by the need to regulate profits and dividends in the interests of managers and shareholders. However, as this change took place within the framework of prudence, it was impossible, at that stage of capitalist accounting, to achieve a perfect smoothing of the rate of accounting profit. The solution to this problem was only to be found at the end of the 20th century with the onset of the third or actuarial stage and the "discovery" of fair value.

<i>Background:</i> Identification of low-income women with the rare but serious risk of hereditary cancer and their referral to appropriate services presents an important public health challenge. We report the results of formative research to reach thousands of women for efficient identification of those at high risk and expedient access to free genetic services. External validity is maximized by emphasizing intervention fit with the two end-user organizations who must connect to make this possible. This study phase informed the design of a subsequent randomized controlled trial. <i>Methods:</i> We conducted a randomized controlled pilot study (n = 38) to compare two intervention models for feasibility and impact. The main outcome was receipt of genetic counseling during a two-month intervention period. Model 1 was based on the usual outcall protocol of an academic hospital genetic risk program, and Model 2 drew on the screening and referral procedures of a statewide toll-free phone line through which large numbers of high-risk women can be identified. In Model 1, the risk program proactively calls patients to schedule genetic counseling; for Model 2, women are notified of their eligibility for counseling and make the call themselves. We also developed and pretested a family history screener for administration by phone to identify women appropriate for genetic counseling. <i>Results:</i> There was no statistically significant difference in receipt of genetic counseling between women randomized to Model 1 (3/18) compared with Model 2 (3/20) during the intervention period. However, when unresponsive women in Model 2 were called after 2 months, 7 more obtained counseling; 4 women from Model 1 were also counseled after the intervention. Thus, the intervention model that closely aligned with the risk program's outcall to high-risk women was found to be feasible and brought more low-income women to free genetic counseling. Our screener was easy to administer by phone and appeared to identify high-risk callers effectively. The model and screener are now in use in the main trial to test the effectiveness of this screening and referral intervention. A validation analysis of the screener is also underway. <i>Conclusion:</i> Identification of intervention strategies and tools, and their systematic comparison for impact and efficiency in the context where they will ultimately be used are critical elements of practice-based research.

Increasing awareness of the finite resources of the planet, including its environmental quality, constitutes a powerful driver for industries and governments not only to fight the effects of pollution but to avoid it at the source. Demands are mounting to replace conventional industrial processes by less- or non-polluting ones. During this gradual shift the treatment of wastes from current human activities and as a legacy of our industrial history remains a challenge. As these treatments merge with environmentally benign industrial processes a truly sustainable economy will become a reality. Enzymes or whole-cell biocatalysts in industrial processes are linked to lower consumption of energy and chemicals and are thus "green" agents. Enzymes catalyze specific reactions under moderate conditions hence they are instrumental for the selective removal of pollutants from waste streams. Enzyme specificity also precludes undesired side-reactions, while in some cases the pollutants treated could be transformed into added-value products, as illustrated in the waste biorefinery concept. The power of such biocatalysts is demonstrated in the case of emerging organic contaminants (EOCs) such as pharmaceuticals and personal care products (PPCPs), which affect treated and untreated water and associated matrices like sludges and sediments at very low but environmentally relevant concentrations ("micropollutants") through unwanted biological effects like endocrine disruption. Oxidative enzymes like fungal laccases and peroxidases are promising biocatalysts for the transformation and removal of the biological effects of EOCs. The re-usability of such enzymes and their separability from reactants and products can be ensured by carrier-based immobilization or by formation of cross-linked enzyme aggregates (CLEAs) which are applied for the treatment of EOCs in adapted reactor systems. We have identified key factors for the production of CLEAs of laccases alone or of combined oxidoreductases (e.g. versatile peroxidase coupled to glucose oxidase), and we have improved these novel biocatalysts by applying rational experimental design and optimization methodologies, as shown in the degradation and detoxification of bisphenol A, a ubiquitous endocrine disruptor. Multi-enzyme biocatalysts co-aggegated in combi-CLEAs showed activity over a broad pH range implying their suitability for the treatment of micropollutant-contaminated real wastewaters of varying pHs. Finally we have prepared novel robust biocatalysts for EOC removal based on laccase encapsulated by biomimetic methodologies. The creative fusion of biocatalysis,chemical engineering fundamentals and nanotechnology opens up attractive horizons towards both sustainable treatment of micropollutant-contaminated matrices and, more generally, multiplies ouroptions for environmentally relevant industrial p rocesses. keywords : enzyme; oxidoreductase; laccase; micropollutant; nanoparticles

This study investigates the history and development of election laws in Jordan in the period from 1928 to 2011. Elections in Jordan have gone through six election laws and dozens of amendments, in addition to instructions issued about them. Many amendments have been introduced about the duration of sessions; the number of election districts; increases in the number of representatives of some election districts; the length of the nomination period; the fees that the candidates for nomination need to pay; the period for election campaigning; the committees established to oversee the voting and sorting of ballots; the authority to declare winning candidates; and polling stations, with the awareness that the development of election laws provides a clear indication of the political, economic and social development that Jordan has witnessed since its foundation up to the present day. The study reached a number of conclusions, such as that the election laws in Jordan has varied among election methods. After beginning with indirect elections, by which representatives are elected in two stages, it shifted to secret direct elections in one stage, by which representatives are directly elected. That was in line with Jordan adopting a parliamentary system in 1947 based on two chambers of representatives and senators in place of the Legislative Council that combined the elected representatives and the representatives from the executive authority into one council. The manner of direct elections did not stipulate that the winning candidates should have a certain percentage of votes, but rather that receiving the highest number of votes was sufficient. The election laws began with open lists that gave the voter the right to choose a number of representatives that did not exceed the number of seats assigned for each election district and changed to a system based on one vote that allowed the voter to select only one candidate. That received wide criticism from different political spectrums, trade associations and civil society organizations, who considered it a reversal to the course of democracy. Despite the criticism, it has remained in force even after the 16th parliamentary elections. The study recommended quickly establishing a modern election law that all political and social groups can agree to. It should respond to the development of politics and lead to national solidarity among the political and economic groups in all the regions of the kingdom, abolishing factionalism, partisanship and sectarianism. Any delay in establishing this law will be at the expense of the political stability in the country.

This empirical paper wants to analyze determinants for regional differences in German unemployment rates using a spatial panel model. The analysis of regional differences is of particular interest in the German case due to its specific history. Twenty-two years after German reunification, there are still structural differences between both parts affecting economic activity. We identify the driving factors in the whole of Germany as well as in East and West Germany separately. To our best knowledge, this study is the first contribution investigating regional unemployment in the reunified Germany. We provide evidence of spatial dependence in regional unemployment data. Taking into account theoretical contributions to this literature, we exploit 24 possible explanatory variables on 412 German districts for the period from 1999 until 2007. To select the relevant variables for our model, we apply a two-step model selection procedure. Firstly, we divide our variables into three groups according to theoretical importance. Secondly, we regress regional unemployment rates on different combinations of variables where the essential variables are always contained. As unemployment data also exhibit temporal dependence, we specify both a static and a dynamic spatial panel model. The spatial econometric literature provides various types of spatial models. To decide which type of spatial model is appropriate in our context, we apply the specification test by Debarsy and Ertur (2010, Reg. Sci. Urban Econ.). The static model specification is estimated using the quasi-maximum likelihood estimator proposed in Lee and Yu (2010, J. Econometrics) and the dynamic model is estimated using the quasi-maximum likelihood estimator proposed by Lee and Yu (2010, Econometric Theory). To incorporate the spatial information into the model, we construct different spatial weights matrices. On the one hand, we use the binary contiguity matrix and, on the other, we apply a distance-based spatial weights matrix as well as the matrix proposed in Molho (1995, J. Reg. Sci.). We extend the existing literature by the following two aspects: Firstly, we apply both a static and a dynamic spatial panel model. Hence, we exploit the panel dimension of our data and, in addition to that, we account for both spatial and temporal dependence in the data. Our results show that the spatial dynamic panel model fits the data in the best way. Secondly, we provide evidence for regional unemployment in Germany being of disequilibrium nature. This finding justifies political interventions on regional labor markets.

La Universidad de las Regiones Autónomas de la Costa Caribe Nicaragüense (URACCAN), tiene presencia en 4 Recintos Universitarios del Caribe. En la Región Autónoma Atlántico Norte en Siuna y Bilwi; en la Región Autónoma Atlántico Sur en Bluefields y Nueva Guinea, se asimilan en relación a la estructura orgánica y líneas de trabajo: extensión, docencia e investigación. El Recinto Siuna-Las Minas surge en 1995, para dar respuesta a una demanda histórica de siglos de exclusión económica, política, cultural y social por parte del Estado nacional nicaragüense. El objeto de esta sistematización fue rescatar la historia y la generación de propuestas alternativas en la construcción de la autonomía de la Costa Atlántica. Es de tipo longitudinal de 1995-2005 y se realizó en el 2007 a partir de un enfoque cualitativo básicamente con entrevistas In situ individuales y grupales, además se estudiaron las memorias de los talleres, actas, resúmenes de los debates, datos estadísticos, evaluaciones y diagnósticos institucionales. Con un enfoque sistémico se ha concluido que en el ámbito nacional la URACCAN por su perfil multiétnico, intercultural bilingüe y su praxis de acompañamiento comunitario con­tribuye al desarrollo identitario en la forja de la Autonomía de la Costa Caribe donde conviven seis culturas: miskitu, sumu-mayangna, rama, garífuna, creol y los pueblos del mestizaje. SUMMARY The University of the Autonomous Regions of the Caribbean Coast of Nicaragua (URACCAN), is present in four Campuses. In the North Atlantic Autonomous Region in Siuna and Bilwi; and in the South Atlantic Autonomous Region in Bluefields and Nueva Guinea, as they are treated in relation to the organizational structure and working lines: extension, teaching and research. The Siuna Campus was founded in 1995, in response to a historical demand of centuries of economic, political, cultural and social exclusion by the Nicaraguan national state. The purpose of this systematization was to rescue the history and the generation of alternative proposals for the construction of the autonomy of the Atlantic Coast. It's a longitudinal study from 1995-2005 and it was carried-out in 2007 from a primarily qualitative approach with individual and group interviews in situ; we also examined the reports of the workshops, the minutes, summaries of discussions, statistics, evaluations and institutional diagnostics. It was concluded -using a systemic approach- that URACCAN at a national context and due to its multiethnic and intercultural-bilingual profile, as well as it community accompaniment praxis contributes to identity development in forging the autonomy of the Caribbean Coast where six cultures coexist: Miskitu, Sumu-Mayangna, Rama, Creole, Garifuna, and Mestizo.