Hypertension: which aspects of hypertension should we impact on and how?

Cardiovascular complications may, to a large extent, be prevented by lowering blood pressure in hypertensive patients. International recommendations currently stress the importance of reaching values of below 140/90 mmHg in each patient or even lower in the case of concomitant diabetes or renal impairment. It is currently considered crucial to control the systolic pressure as well as the diastolic pressure, in particular because the relationship between cardiovascular risk and blood pressure is closer for the systolic than the diastolic value. An increase in systolic pressure is in itself a sign of the stiffening of the arterial tree. In most patients, the target pressure may only be reached by combining several different antihypertensive agents. In the STRATHE Study, a greater antihypertensive efficacy, in particular on systolic pressure, was obtained by instituting treatment with a fixed low-dose combination of an angiotensin-converting enzyme inhibitor (perindopril) and a diuretic (indapamide), in comparison with other therapeutic strategies based on single-agent therapy. Fixed-dose antihypertensive combinations have now become a validated option for initiating antihypertensive treatment.

Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.

BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.

A peripheral dose calculation model for estimating second cancer risk after breast radiotherapy

AbstractBreast cancer is one of the most common cancers affecting one in eight women during their lives. Survival rates have increased steadily thanks to early diagnosis with mammography screening and more efficient treatment strategies. Post-operative radiation therapy is a standard of care in the management of breast cancer and has been shown to reduce efficiently both local recurrence rate and breast cancer mortality. Radiation therapy is however associated with some late effects for long-term survivors. Radiation-induced secondary cancer is a relatively rare but severe late effect of radiation therapy. Currently, radiotherapy plans are essentially optimized to maximize tumor control and minimize late deterministic effects (tissue reactions) that are mainly associated with high doses (» 1 Gy). With improved cure rates and new radiation therapy technologies, it is also important to evaluate and minimize secondary cancer risks for different treatment techniques. This is a particularly challenging task due to the large uncertainties in the dose-response relationship.In contrast with late deterministic effects, secondary cancers may be associated with much lower doses and therefore out-of-field doses (also called peripheral doses) that are typically inferior to 1 Gy need to be determined accurately. Out-of-field doses result from patient scatter and head scatter from the treatment unit. These doses are particularly challenging to compute and we characterized it by Monte Carlo (MC) calculation. A detailed MC model of the Siemens Primus linear accelerator has been thoroughly validated with measurements. We investigated the accuracy of such a model for retrospective dosimetry in epidemiological studies on secondary cancers. Considering that patients in such large studies could be treated on a variety of machines, we assessed the uncertainty in reconstructed peripheral dose due to the variability of peripheral dose among various linac geometries. For large open fields (> 10x10 cm2), the uncertainty would be less than 50%, but for small fields and wedged fields the uncertainty in reconstructed dose could rise up to a factor of 10. It was concluded that such a model could be used for conventional treatments using large open fields only.The MC model of the Siemens Primus linac was then used to compare out-of-field doses for different treatment techniques in a female whole-body CT-based phantom. Current techniques such as conformai wedged-based radiotherapy and hybrid IMRT were investigated and compared to older two-dimensional radiotherapy techniques. MC doses were also compared to those of a commercial Treatment Planning System (TPS). While the TPS is routinely used to determine the dose to the contralateral breast and the ipsilateral lung which are mostly out of the treatment fields, we have shown that these doses may be highly inaccurate depending on the treatment technique investigated. MC shows that hybrid IMRT is dosimetrically similar to three-dimensional wedge-based radiotherapy within the field, but offers substantially reduced doses to out-of-field healthy organs.Finally, many different approaches to risk estimations extracted from the literature were applied to the calculated MC dose distribution. Absolute risks varied substantially as did the ratio of risk between two treatment techniques, reflecting the large uncertainties involved with current risk models. Despite all these uncertainties, the hybrid IMRT investigated resulted in systematically lower cancer risks than any of the other treatment techniques. More epidemiological studies with accurate dosimetry are required in the future to construct robust risk models. In the meantime, any treatment strategy that reduces out-of-field doses to healthy organs should be investigated. Electron radiotherapy might offer interesting possibilities with this regard.RésuméLe cancer du sein affecte une femme sur huit au cours de sa vie. Grâce au dépistage précoce et à des thérapies de plus en plus efficaces, le taux de guérison a augmenté au cours du temps. La radiothérapie postopératoire joue un rôle important dans le traitement du cancer du sein en réduisant le taux de récidive et la mortalité. Malheureusement, la radiothérapie peut aussi induire des toxicités tardives chez les patients guéris. En particulier, les cancers secondaires radio-induits sont une complication rare mais sévère de la radiothérapie. En routine clinique, les plans de radiothérapie sont essentiellement optimisées pour un contrôle local le plus élevé possible tout en minimisant les réactions tissulaires tardives qui sont essentiellement associées avec des hautes doses (» 1 Gy). Toutefois, avec l'introduction de différentes nouvelles techniques et avec l'augmentation des taux de survie, il devient impératif d'évaluer et de minimiser les risques de cancer secondaire pour différentes techniques de traitement. Une telle évaluation du risque est une tâche ardue étant donné les nombreuses incertitudes liées à la relation dose-risque.Contrairement aux effets tissulaires, les cancers secondaires peuvent aussi être induits par des basses doses dans des organes qui se trouvent hors des champs d'irradiation. Ces organes reçoivent des doses périphériques typiquement inférieures à 1 Gy qui résultent du diffusé du patient et du diffusé de l'accélérateur. Ces doses sont difficiles à calculer précisément, mais les algorithmes Monte Carlo (MC) permettent de les estimer avec une bonne précision. Un modèle MC détaillé de l'accélérateur Primus de Siemens a été élaboré et validé avec des mesures. La précision de ce modèle a également été déterminée pour la reconstruction de dose en épidémiologie. Si on considère que les patients inclus dans de larges cohortes sont traités sur une variété de machines, l'incertitude dans la reconstruction de dose périphérique a été étudiée en fonction de la variabilité de la dose périphérique pour différents types d'accélérateurs. Pour de grands champs (> 10x10 cm ), l'incertitude est inférieure à 50%, mais pour de petits champs et des champs filtrés, l'incertitude de la dose peut monter jusqu'à un facteur 10. En conclusion, un tel modèle ne peut être utilisé que pour les traitements conventionnels utilisant des grands champs.Le modèle MC de l'accélérateur Primus a été utilisé ensuite pour déterminer la dose périphérique pour différentes techniques dans un fantôme corps entier basé sur des coupes CT d'une patiente. Les techniques actuelles utilisant des champs filtrés ou encore l'IMRT hybride ont été étudiées et comparées par rapport aux techniques plus anciennes. Les doses calculées par MC ont été comparées à celles obtenues d'un logiciel de planification commercial (TPS). Alors que le TPS est utilisé en routine pour déterminer la dose au sein contralatéral et au poumon ipsilatéral qui sont principalement hors des faisceaux, nous avons montré que ces doses peuvent être plus ou moins précises selon la technTque étudiée. Les calculs MC montrent que la technique IMRT est dosimétriquement équivalente à celle basée sur des champs filtrés à l'intérieur des champs de traitement, mais offre une réduction importante de la dose aux organes périphériques.Finalement différents modèles de risque ont été étudiés sur la base des distributions de dose calculées par MC. Les risques absolus et le rapport des risques entre deux techniques de traitement varient grandement, ce qui reflète les grandes incertitudes liées aux différents modèles de risque. Malgré ces incertitudes, on a pu montrer que la technique IMRT offrait une réduction du risque systématique par rapport aux autres techniques. En attendant des données épidémiologiques supplémentaires sur la relation dose-risque, toute technique offrant une réduction des doses périphériques aux organes sains mérite d'être étudiée. La radiothérapie avec des électrons offre à ce titre des possibilités intéressantes.

Barcoding human physical activity to assess chronic pain conditions.

BACKGROUND: Modern theories define chronic pain as a multidimensional experience - the result of complex interplay between physiological and psychological factors with significant impact on patients' physical, emotional and social functioning. The development of reliable assessment tools capable of capturing the multidimensional impact of chronic pain has challenged the medical community for decades. A number of validated tools are currently used in clinical practice however they all rely on self-reporting and are therefore inherently subjective. In this study we show that a comprehensive analysis of physical activity (PA) under real life conditions may capture behavioral aspects that may reflect physical and emotional functioning.¦METHODOLOGY: PA was monitored during five consecutive days in 60 chronic pain patients and 15 pain-free healthy subjects. To analyze the various aspects of pain-related activity behaviors we defined the concept of PA 'barcoding'. The main idea was to combine different features of PA (type, intensity, duration) to define various PA states. The temporal sequence of different states was visualized as a 'barcode' which indicated that significant information about daily activity can be contained in the amount and variety of PA states, and in the temporal structure of sequence. This information was quantified using complementary measures such as structural complexity metrics (information and sample entropy, Lempel-Ziv complexity), time spent in PA states, and two composite scores, which integrate all measures. The reliability of these measures to characterize chronic pain conditions was assessed by comparing groups of subjects with clinically different pain intensity.¦CONCLUSION: The defined measures of PA showed good discriminative features. The results suggest that significant information about pain-related functional limitations is captured by the structural complexity of PA barcodes, which decreases when the intensity of pain increases. We conclude that a comprehensive analysis of daily-life PA can provide an objective appraisal of the intensity of pain.

Systemic effects of epidural Methylprednisolone injection on glucose tolerance in diabetic patients.

ABSTRACT: BACKGROUND: Several studies have shown that in diabetic patients, the glycemic profile was disturbed after intra-articular injection of corticosteroids. Little is known about the impact of epidural injection in such patients. The goal of this study was double, at first comparing the glycaemic profile in diabetic patients after a unique injection of 80 mg of acetate methylprednisolone either intra-articular or epidural and secondly to compare the amount of systemic diffusion of the drug after both procedures. METHODS: Seventeen patients were included. Glycemic changes were compared in 9 diabetic patients following intra-articular (4 patients) and epidural injections (5 patients). Epidural injections were performed using the sacral route under fluoroscopic control in patients with lumbar spinal stenosis. Diabetes control had to stable for more than 10 days and the renal function to be preserved. Blood glucose was monitored using a validated continuous measuring device (GMS, Medtronic) the day before and for two days following the injection. Results were expressed in the form of daily glycemic profiles and as by mean, peak and minimal values +/ SD. The urinary excretion of methylprednisolone after the 2 routes of injection was analyzed in 8 patients (4 in each group). Urine samples were cropped one hour before the injections, then 4 times during the first day and 3 times a week for 2 weeks. The measurements included the free and conjugated fraction RESULTS: The glycaemic profile remains unchanged with no significant changes in the group of the 5 diabetic patients receiving epidural injections. On the other end, the average peak and mean values were enhanced up to 3 mmol/l above baseline two days after the infiltration in the groups of the 4 diabetic patients infiltrated intra-articular. The mean urinary excretion of the steroid was about ten times higher in the intra-articular versus epidural group: 7000 ng/ml versus 700 ng/ml. Looking at each individual there were marked differences especially after intra-articular injections. CONCLUSION: This is the first study to show that a single epidural steroid injection of 80 mg depot methylprednisolone had no effect on the glycemic control in diabetic patients. The absence of glycemic control changes correlated well with the very low urinary excretion of the drug after epidural injection. Trial registration NCT01420497.

Glioprotective impact of cell-permeable peptides in preclinical models of amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons. It is mostly sporadic, but about 2% of cases are associated with mutations in the gene encoding the enzyme superoxide dismutase 1 (SOD1). A major constraint to the comprehension of the pathogenesis of ALS has been long represented by the conviction that this disorder selectively affects motor neurons in a cell-autonomous manner. However, the failure to identify the events underlying the neurodegenerative process and the increased knowledge of the complex cellular interactions necessary for the correct functioning of the CNS has recently focused the attention on the contribution to neurodegeneration of glial cells, including astrocytes. Astrocytes can hurt motor neurons directly by secreting neurotoxic factors, but they can also play a deleterious role indirectly by losing functions that are supportive for neurons. Recently, we reported that a subpopulation of astrocytes degenerates in the spinal cord of hSOD1G93A transgenic mouse model of ALS. Mechanistic studies in cultured astrocytes revealed that such effect is mediated by the excitatory amino acid glutamate.On the bsis of these observations, we next used the established cell culture model as a tool to screen the glioprotective effect of innovative drugs, namely cell-permeable therapeutics. These consist of peptidic effector moieties coupled to the selective intracellular peptide transporter TAT protein. We initially validated the usefulness of these molecules demonstrating that a control fluorescent peptide enters astrocytes in culture and is retained within the cells up to 24-48 h, according to the timing of our cytotoxicity experiments. We then tested the impact of specific intracellular peptides with antiapoptotic properties on glutamate-treated hSOD1G93A- expressing astrocytes and we identified one molecule that protects the cells from death. Chronic treatment of ALS mice with this peptide had a positive impact on the outcome of the disease.

The value of 'positive' clinical signs for weakness, sensory and gait disorders in conversion disorder: a systematic and narrative review.

Experts in the field of conversion disorder have suggested for the upcoming DSM-V edition to put less weight on the associated psychological factors and to emphasise the role of clinical findings. Indeed, a critical step in reaching a diagnosis of conversion disorder is careful bedside neurological examination, aimed at excluding organic signs and identifying 'positive' signs suggestive of a functional disorder. These positive signs are well known to all trained neurologists but their validity is still not established. The aim of this study is to provide current evidence regarding their sensitivity and specificity. We conducted a systematic search on motor, sensory and gait functional signs in Embase, Medline, PsycINfo from 1965 to June 2012. Studies in English, German or French reporting objective data on more than 10 participants in a controlled design were included in a systematic review. Other relevant signs are discussed in a narrative review. Eleven controlled studies (out of 147 eligible articles) describing 14 signs (7 motor, 5 sensory, 2 gait) reported low sensitivity of 8-100% but high specificity of 92-100%. Studies were evidence class III, only two had a blinded design and none reported on inter-rater reliability of the signs. Clinical signs for functional neurological symptoms are numerous but only 14 have been validated; overall they have low sensitivity but high specificity and their use should thus be recommended, especially with the introduction of the new DSM-V criteria.

Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy.

Central serous chorioretinopathy (CSCR) is a vision-threatening eye disease with no validated treatment and unknown pathogeny. In CSCR, dilation and leakage of choroid vessels underneath the retina cause subretinal fluid accumulation and retinal detachment. Because glucocorticoids induce and aggravate CSCR and are known to bind to the mineralocorticoid receptor (MR), CSCR may be related to inappropriate MR activation. Our aim was to assess the effect of MR activation on rat choroidal vasculature and translate the results to CSCR patients. Intravitreous injection of the glucocorticoid corticosterone in rat eyes induced choroidal enlargement. Aldosterone, a specific MR activator, elicited the same effect, producing choroid vessel dilation -and leakage. We identified an underlying mechanism of this effect: aldosterone upregulated the endothelial vasodilatory K channel KCa2.3. Its blockade prevented aldosterone-induced thickening. To translate these findings, we treated 2 patients with chronic nonresolved CSCR with oral eplerenone, a specific MR antagonist, for 5 weeks, and observed impressive and rapid resolution of retinal detachment and choroidal vasodilation as well as improved visual acuity. The benefit was maintained 5 months after eplerenone withdrawal. Our results identify MR signaling as a pathway controlling choroidal vascular bed relaxation and provide a pathogenic link with human CSCR, which suggests that blockade of MR could be used therapeutically to reverse choroid vasculopathy.

Relative protein quantification by isobaric SILAC with immonium ion splitting (ISIS)

Metabolic labeling techniques have recently become popular tools for the quantitative profiling of proteomes. Classical stable isotope labeling with amino acids in cell cultures (SILAC) uses pairs of heavy/light isotopic forms of amino acids to introduce predictable mass differences in protein samples to be compared. After proteolysis, pairs of cognate precursor peptides can be correlated, and their intensities can be used for mass spectrometry-based relative protein quantification. We present an alternative SILAC approach by which two cell cultures are grown in media containing isobaric forms of amino acids, labeled either with 13C on the carbonyl (C-1) carbon or 15N on backbone nitrogen. Labeled peptides from both samples have the same nominal mass and nearly identical MS/MS spectra but generate upon fragmentation distinct immonium ions separated by 1 amu. When labeled protein samples are mixed, the intensities of these immonium ions can be used for the relative quantification of the parent proteins. We validated the labeling of cellular proteins with valine, isoleucine, and leucine with coverage of 97% of all tryptic peptides. We improved the sensitivity for the detection of the quantification ions on a pulsing instrument by using a specific fast scan event. The analysis of a protein mixture with a known heavy/light ratio showed reliable quantification. Finally the application of the technique to the analysis of two melanoma cell lines yielded quantitative data consistent with those obtained by a classical two-dimensional DIGE analysis of the same samples. Our method combines the features of the SILAC technique with the advantages of isobaric labeling schemes like iTRAQ. We discuss advantages and disadvantages of isobaric SILAC with immonium ion splitting as well as possible ways to improve it

Ecologia de les Invasions Ecològiques

La paradoxa de les invasions planteja com és possible que algunes espècies siguin capaces d'envair regions a les que no han evolucionat i, fins i tot, arribar a ser més abundants que espècies autòctones que han tingut més oportunitat d’adaptars’hi. Comprendre l’ecologia de les invasions és especialment interessant perquè algunes d’aquestes espècies causen greus impactes ecològics i econòmics arreu del món. Per intentar resoldre la paradoxa en aquest treball s’ha seguit dues aproximacions. Per una banda, mitjançant anàlisis comparatius s’ha volgut identificar aquelles característiques que afecten el resultat de les introduccions d’ocells, i utilitzar-les com a predictors en protocols d’avaluació de riscos per prevenir futures invasions. Seguint en aquest nivell d’aproximació també s’ha volgut validar si, tal com prediu la teoria ecològica, les estratègies vitals de les espècies afecten l'èxit en l'establiment de poblacions d'ocells exòtics. D'altra banda, a través d'aproximacions descriptives i experimentals, s’ha volgut investigar els mecanismes d’invasió en un cas d’estudi concret, el del Rossinyol del Japó (Leiothrix lutea) als boscos de Collserola (Barcelona). Els anàlisis comparatius han mostrat que és possible de predir la probabilitat d’establiment de les espècies introduïdes a partir d’unes poques característiques amb notable precisió. Altrament, l’anàlisi sobre l’efecte de les estratègies vitals sobre el resultat de les invasions sembla indicar que hi ha un biaix en el registre històric d’introduccions que impedeix descobrir la naturalesa d’aquesta relació i suggereixen buscar una aproximació alternativa per al problema. Respecte el cas del Rossinyol del Japó, els resultats preliminars suggereixen que les raons del seu èxit als boscos de Collserola podrien ser que ha trobat un nínxol ecològic que està poc aprofitat per les espècies natives. Aquest treball vol mostrar com a través de la integració de diferents aproximacions podem ser capaços d’aportar una visió més completa per comprendre la paradoxa de les invasions.

Laser scanning-based recognition of rotational movements on a deep seated gravitational instability: The Cinque Torri case (North-Eastern Italian Alps)

The Cinque Torri group (Cortina d'Ampezzo, Italy) is an articulated system of unstable carbonatic rock monoliths located in a very important tourism area and therefore characterized by a significant risk. The instability phenomena involved represent an example of lateral spreading developed over a larger deep seated gravitational slope deformation (DSGSD) area. After the recent fall of a monolith of more than 10 000 m3, a scientific study was initiated to monitor the more unstable sectors and to characterize the past movements as a fundamental tool for predicting future movements and hazard assessment. To achieve greater insight on the ongoing lateral spreading process, a method for a quantitative analysis of rotational movements associated with the lateral spreading has been developed, applied and validated. The method is based on: i) detailed geometrical characterization of the area by means of laser scanner techniques; ii) recognition of the discontinuity sets and definition of a reference frame for each set, iii) correlation between the obtained reference frames related to a specific sector and a stable external reference frame, and iv) determination of the 3D rotations in terms of Euler angles to describe the present settlement of the Cinque Torri system with respect to the surrounding stable areas. In this way, significant information on the processes involved in the fragmentation and spreading of a former dolomitic plateau into different rock cliffs has been gained. The method is suitable to be applied to similar case studies.

Validation of a score for predicting fatal bleeding in patients receiving anticoagulation for venous thromboembolism.

BACKGROUND: The only available score to assess the risk for fatal bleeding in patients with venous thromboembolism (VTE) has not been validated yet. METHODS: We used the RIETE database to validate the risk-score for fatal bleeding within the first 3 months of anticoagulation in a new cohort of patients recruited after the end of the former study. Accuracy was measured using the ROC curve analysis. RESULTS: As of December 2011, 39,284 patients were recruited in RIETE. Of these, 15,206 had not been included in the former study, and were considered to validate the score. Within the first 3 months of anticoagulation, 52 patients (0.34%; 95% CI: 0.27-0.45) died of bleeding. Patients with a risk score of <1.5 points (64.1% of the cohort) had a 0.10% rate of fatal bleeding, those with a score of 1.5-4.0 (33.6%) a rate of 0.72%, and those with a score of >4 points had a rate of 1.44%. The c-statistic for fatal bleeding was 0.775 (95% CI 0.720-0.830). The score performed better for predicting gastrointestinal (c-statistic, 0.869; 95% CI: 0.810-0.928) than intracranial (c-statistic, 0.687; 95% CI: 0.568-0.806) fatal bleeding. The score value with highest combined sensitivity and specificity was 1.75. The risk for fatal bleeding was significantly increased (odds ratio: 7.6; 95% CI 3.7-16.2) above this cut-off value. CONCLUSIONS: The accuracy of the score in this validation cohort was similar to the accuracy found in the index study. Interestingly, it performed better for predicting gastrointestinal than intracranial fatal bleeding.

Can the trabecular bone score be considered as a major clinical risk factor of osteoporotic fractures? A meta-like analysis.

To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist. Out of these factors many of them are indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 cross-sectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest compared with the middle TBS tertile was 1.55[1.46-1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

Laboratory indicators for monitoring HIV disease

Immunological monitoring of disease progression following HIV infection and seroconversion illness, latency and AIDS, not only helps in the basic investigation of the natural history of the viral infection in man, but also can assist in prognosis and treatment of AIDS-defining illnesses. However, outside clinical trials, these tests should be selected and used in clinical practice only if they are validated as relevant and effective. The absolute CD4+ T-helper lymphocyte count, measured by flow cytometry, has emerged as the best available investigation, but needs care in sampling due to diurnal and circadian rhythms, effects of age, pregnancy, therapy, intercurrent infections and technique. Sampling should provide a baseline and trends - monthly intervals initially, then quarterly in uncomplicated cases. Thresholds may be given for counts (e.g. 200/µl) below which prophylaxis against pneumocystis pneumonia should be administered, and repeating persistently low counts (e.g. below 50/µl) is seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and immunoglobulins rarely add information. Physicians and laboratories should have testing guidelines based on clinical audit of best practice, based in turn on scientific understanding of the immunological processes involved.

Els cultius in vitro i el desenvolupament vegetal

Biotecnologia Vegetal de materials de treball que incorporin les TICs. El material elaborat ha estat un llibre electrònic utilitzable tant on-line (web) com off-line (CD). Els materials generats com a resultes d’aquest projecte han estat situats en un servidor de la UdL accessible des de l’exterior de la Universitat. Aquest llibre electrònic és d’accés obert i es pot consultar on-line a l’URL (http://sakai.udl.es/cursos/76304/indexC.htm). El llibre electrònic conté un total de 98 Mb d’informació hipermèdia i hipertexual distribuïda en més de 380 arxius dels quals 50 són pàgines html, 10 arxius doc, 10 arxius pdf, 258 imatges fixes i 8 arxius de vídeo en format flash (swf). L’accés al llibre electrònic es realitza a través d’una pantalla inicial que dóna pas a un menú que distribueix els materials en 7 apartats. Els textos estan acompanyats de gran quantitat d’imatges fotogràfiques, gràfics, esquemes, imatges infogràfiques i videoclips generats de novo per aquest projecte. En dissenyar la web s’han tingut en compte criteris de confiabilitat, accessibilitat i usabilitat. El primer disseny de la web ha estat validat per un panel d’usuaris i utilitzat posteriorment amb alumnes durant el curs 2007-2008. Les observacions i suggeriments fets per aquests ja han estat incorporats en aquest document final. Una primera enquesta de satisfacció realitzada amb aquest alumnat permet concloure, a títol provisional donat lo reduït de la població enquestada, que l’alumnat mostra un grau de coneixement de les eines TIC suficient i que consideren positiva la incorporació de materials multimèdia com a recurs educatiu. A més a més, la realització d’aquest projecte i la seva aplicació a l’aula ha estat presentada en dues ponències al “Congreso Internacional de Docencia y Innovación Universitaria”.