Maxime Quijoux, Adieux au patronat. Lutte et gestion ouvrières dans une usine reprise en coopérative

L’ouvrage du sociologue Maxime Quijoux relate une expérience sociale a priori improbable. Des salariés d’une imprimerie menacée de fermeture parviennent en 2012, sous l’impulsion de la Confédération générale du travail (CGT), à reprendre leur entreprise sous forme de société coopérative et participative (Scop) : ils sauvent 80 emplois, relancent l’activité et mettent en place des formes alternatives de gestion. En revenant sur les différentes étapes de cette reprise d’entreprise, l’auteur pré..

Die operative Therapie der Spondylodiszitis : Eine Verlaufsuntersuchung an der Klinik für Neurochirurgie der Universitätsklinik des Saarlandes

Hintergrund Die Spondylodiszitis ist eine seltene Erkrankung, welche jedoch bei einer alternden Gesellschaft und einem höheren Anteil an immunsupprimierten und multimorbiden Patienten eine steigende Inzidenz aufzeigt. Die optimale Therapie wurde bisher nicht festgelegt. Es muss zwischen der konservativen und der operativen Versorgung entschieden werden. Ziel dieser Arbeit ist es, das klinische Ergebnis nach operativer Therapie zu evaluieren und Faktoren herauszuarbeiten, die Einfluss haben hinsichtlich des peri- und postoperativen Verlaufs. Methoden Es wurden alle Patienten, welche zwischen dem 01.01.2011 und dem 03.06.2015 konsekutiv an der Klinik für Neurochirurgie der Universität des Saarlandes bei primärer Spondylodiszitis operiert wurden, identifiziert. Die elektronische Patientenakte wurde genutzt um folgende Daten zu erheben: Patientencharakteristika, prä-, intra-, und post-operative Daten sowie Informationen zur ambulanten Verlaufsuntersuchung. Besonderes Augenmerk wurde auf die Operationsberichte bezüglich operativer Verfahren, die stationären Arztberichte sowie die ambulanten Briefe der Kontrolluntersuchungen gelegt. Diese Daten wurden tabellarisch in Excel und SPSS festgehalten und analysiert. Zudem erfolgte zum besseren Vergleich die Einteilung des Patientenguts in verschiedene Gruppen: Patienten mit oder ohne instrumentelle Stabilisierung im Rahmen der ersten Operation, Patienten welche im Verlauf überlebten oder verstarben, Patienten mit einem Alter unter oder über 70 Jahren sowie Patienten mit einem eigens konzipiertem MRT-Score unter oder über 5 Punkten. Ergebnisse Insgesamt wurden 131 (78 männlich und 53 weiblich) Patienten im Zeitraum vom 01.01.2011 bis zum 03.06.2015 operativ behandelt. Diese 131 Patienten wurden insgesamt 144-mal stationär zur operativen Therapie aufgenommen. Insgesamt 10 Patienten mussten wiederholt stationär aufgenommen werden. Das Durchschnittsalter betrug 68 Jahre und die durchschnittlich stationäre Verweildauer lag bei 22,17 Tagen. Die präoperativen Beschwerden bestanden im Durchschnitt seit 37,67 Tagen. In 92,30% der Fälle waren lokale Schmerzen der Wirbelsäule die führende Beschwerdesymptomatik und in 66,67% wiesen die Patienten eine neurologische Symptomatik auf; Paresen waren bei 47,92% aller Patienten nachweisbar. Im Durchschnitt litten die Patienten an 3,17 Komorbiditäten und wiesen einen Risikofaktor (Nikotinabusus, Alkoholabusus, Über- oder Untergewicht) auf. Insgesamt waren 72,06% der Patienten übergewichtig; der Durchschnitts-BMI betrug 28,06. Bei 28,47% der Patienten waren die Kriterien einer Sepsis erfüllt. Insgesamt sind 10,69% der Patienten verstorben. In 14 Fällen war die Spondylodiszitis im Bereich der Halswirbelsäule, in 45 Fällen im Areal der Brustwirbelsäule und in 85 Fällen im Abschnitt der Lendenwirbelsäule lokalisiert. In 53 Fällen wurden die Patienten im ersten operativen Eingriff ohne und in 78 Fällen mit interner Stabilisierung versorgt. Patienten, welche im Rahmen der ersten Operation keine interne Stabilisierung erhielten, mussten signifikant häufiger aufgrund einer persistierenden Infektion erneut operiert werden, als die Patienten, welche bereits innerhalb des ersten Eingriffes eine instrumentelle Versorgung zur Stabilisierung erhielten (32,08% vs. 0%). Aus dem gesamten Patientengut stellten sich 43,75% zur Verlaufskontrolle ambulant vor. 37,5% der Patienten klagten weiterhin über lokale Schmerzen als häufigstes Symptom. In einer erfolgten MRT-Kontrolle waren zu 81,81% keine entzündlichen Formationen im Bereich der betroffenen Lokalisation zu verzeichnen. Nach Untersuchung der Vergleichsgruppen konnte festgehalten werden, dass eine alleinige Dekompression eine ausreichende Behandlung darstellen kann bei jedoch zeitgleich erhöhtem Risiko einer persistieren Infektion, sodass es im Falle mehrerer Operationen doch einer internen Stabilisierung zur ausreichenden Sanierung bedarf. Zudem konnten Faktoren wie männliches Geschlecht, Vorliegen einer Sepsis, einer Niereninsuffizienz, einer respiratorischen Insuffizienz, einer Querschnittsymptomatik oder Paresen, eine hohe Anzahl an Komorbiditäten sowie eine hohe Anzahl an betroffenen Segmenten als negative prognostische Faktoren identifiziert werden. Weiterhin hat sich gezeigt, dass die Patientengruppen mit einem Alter unter oder über 70 Jahren keine relevanten Unterschiede in Bezug auf Patientencharakteristika und Verlauf vorweisen, wie auch in der Gruppe der Patienten mit einem MRT-Score unter oder über 5 Punkten. Schlussfolgerung Bei der Spondylodiszitis handelt es sich um eine infektiöse Erkrankung des höheren Alters. Die Diagnosestellung erfolgt meist verzögert bei länger bestehender Symptomatik. Mittels ausführlicher Anamnese, Erregerdiagnostik, Bildgebung und histologischer Gewebeuntersuchung kann eine sichere Diagnose gestellt werden. Es empfiehlt sich eine frühzeitige antibiotische Behandlung sowie operative Therapie mit oder ohne interne Stabilisierung. Im Rahmen der Verlaufskontrolle sollte besonderes Augenmerk auf die Schmerzsymptomatik sowie die neurologischen Beschwerden gelegt werden. Um ein mögliches Rezidiv frühzeitig zu erkennen sind laborchemische und bildgebende Kontrollen im Verlauf empfehlenswert.Background Spondylodiscitis is a rare infection which shows an increasing incidence due to an aging society and a higher rate of immunosuppressed and multimorbid patients. An ideal therapy has not been defined yet; the decision has to be made between conservative and surgical treatment. The aim of this dissertation is to evaluate the patients´ clinical outcome after surgical management and to define factors which may have an influence on the peri- and postsurgical development. Methods All the patients with primary spondylodiscitis surgically treated from 01.01.2011 to 03.06.2015 at the neurosurgical Hospital from the University from Saarland were identified. The patients´ electronic files were used to collect following data: patients´ characteristics, pre-, intra-, and postsurgical data as well as information of the follow-up examination. Special attention was paid to the surgical report in terms of surgical procedure, the medical report, and the ambulant control documents. This data was tabulated via Excel and SPSS for analytical purpose. For better comparison, patients were assigned to different groups: patients with or without internal stabilisation during the first surgery, patients who survived or died, patients aged under or over 70 years, and patients with a specially developed MRI-score under or over 5 points. Results A total of 131 (78 male and 53 female) patients received surgical therapy from 01.01.2011 to 03.06.2015. Those 131 patients were hospitalised for a total of 144 stationary admissions. 10 patients needed to get hospitalised multiple times. The average age was 68 years and the patients were hospitalised on average for 22,17 days. The clinical symptoms presented themselves for 37,67 days until hospitalisation. A total of 92,30% of patients reported back-pain and 66,67% showed neurological symptoms; paresis was seen in 47,92% of cases. Patients had in mean 3,17 comorbidities and showed one risk factor (nicotine abuse, alcohol abuse, over- or underweight). All in all, 72,06% of the patients were overweight; the average BMI was 28,36. Altogether 28,47% of the patients fulfilled criteria of septicaemia and 10,69% of patients died. In 14 cases the spondylodiscitis was localised on the cervical spine, in 45 cases on the thoracic region, and in 85 cases on the lumbar spine. During the first surgery, 53 patients received decompression without medical implant and 78 patients received decompression with internal stabilisation. Patients who received decompression only during the first surgery needed another surgical intervention due to a persistent infection significantly more often than patients who received internal stabilisation during the first intervention (32,08% vs. 0%). Patients came to a follow-up control in 43,75%, at which 37,5% of the patients complained about local pain as most presenting symptom. An MRI-control showed in 81,81% no sign of infection in the affected region. After analysis of the different groups we can conclude that decompression alone can represent a sufficient therapy but with a higher risk of persistent infection at the same time, so that in case of multiple surgeries needed, an internal stabilisation is required to clear the infection. Furthermore, factors as male sex, septicaemia, renal or respiratory insufficiency, symptoms of paraplegia or paresis, high number of comorbidities, and high number of affected segments can be identified as negative prognostic factors. Additionally, there was no relevant difference noted in relation to characteristics and outcome between patients aged under or over 70 years as well as between patients with an MRI-score under or over 5 points. Conclusion As a result, we can conclude that spondylodiscitis is an infectious disease of the elderly. The steps from symptoms to diagnosis are often delayed. A safe diagnosis can be made through detailed anamnesis, pathogen diagnostics, imaging, and histological proof. We suggest an early antibiotic treatment and surgical therapy with or without internal stabilisation. Pain and neurological symptoms should be given extra attention during follow-up controls. Moreover, we suggest laboratory tests and imaging controls to detect a possible recurrence at the earliest time possible

Prescribing for acute childhood infections in developing and transitional countries, 1990–2009

Background: Evidence of global progress in treating acute paediatric infections is lacking. Objectives: To assess progress over two decades in prescribing for childhood infections and interventions to improve treatment by reviewing empirical evidence in developing and transitional countries. Methods: Data were systematically extracted on the use of medicines for diarrhoea, respiratory infections and malaria from published and unpublished studies (1990–2009) in children under 5 years of age. Medians of each indicator were calculated across studies by study year, geographic region, sector, country income level and prescriber type. To estimate intervention effects from studies meeting methodologically accepted design criteria [randomised controlled trials (RCTs), pre-post with control, and time series studies], the medians of the median effect sizes (median MES) were calculated across outcome measures. Results: Data were extracted from 344 studies conducted in 78 countries with 394 distinct study groups in public (64%), private (22%) and other facilities to estimate trends over time. Of 226 intervention studies, only the 44 (19%) with an adequate study design were used to estimate intervention effects. Over time, use of anti-diarrhoeals for acute diarrhoea decreased significantly (P<0·01). However, treatment of malaria and acute respiratory infection remained largely sub-optimal. Multi-component interventions resulted in larger improvements than single-component ones. The median MES indicated a 28% improvement with community case-management, an 18% improvement with provider education combined with consumer education, but only 9% improvement with provider education alone. Conclusions: While diarrhoea treatment has improved over the last 20 years, treatment of other childhood illnesses remains sub-optimal. Multi-component interventions demonstrated some success in improving management of acute childhood illness

Disentagling and Connecting Different Perspectives on Prosodic Prominence

Wagner P, Origlia A, Avesani C, et al. Disentagling and Connecting Different Perspectives on Prosodic Prominence. Presented at the ICPL 2015, Cologne

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Reduced anthropogenic aerosol radiative forcing caused by biogenic new particle formation

The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol-cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20-100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by 0.22 W m-2 (27%) to -0.60 W m-2. Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria.

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves artemisinin-like kill kinetics in vitro with a parasite clearance time of \u3c24 h. A single dose of 30 mg/kg is fully curative in the Pf-humanized severe combined immunodeficient mouse model. INE963 (1) also exhibits a high barrier to resistance in drug selection studies and a long half-life (T1/2) across species. These properties suggest the significant potential for INE963 (1) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 (1) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials

IGF-1, IGFBP-1, and IGFBP-3 Polymorphisms Predict Circulating IGF Levels but Not Breast Cancer Risk: Findings from the Breast and Prostate Cancer Cohort Consortium (BPC3)

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women

Global Regulatory Functions of the Staphylococcus aureus Endoribonuclease III in Gene Expression

RNA turnover plays an important role in both virulence and adaptation to stress in the Gram-positive human pathogen Staphylococcus aureus. However, the molecular players and mechanisms involved in these processes are poorly understood. Here, we explored the functions of S. aureus endoribonuclease III (RNase III), a member of the ubiquitous family of double-strand-specific endoribonucleases. To define genomic transcripts that are bound and processed by RNase III, we performed deep sequencing on cDNA libraries generated from RNAs that were co-immunoprecipitated with wild-type RNase III or two different cleavage-defective mutant variants in vivo. Several newly identified RNase III targets were validated by independent experimental methods. We identified various classes of structured RNAs as RNase III substrates and demonstrated that this enzyme is involved in the maturation of rRNAs and tRNAs, regulates the turnover of mRNAs and non-coding RNAs, and autoregulates its synthesis by cleaving within the coding region of its own mRNA. Moreover, we identified a positive effect of RNase III on protein synthesis based on novel mechanisms. RNase III–mediated cleavage in the 5′ untranslated region (5′UTR) enhanced the stability and translation of cspA mRNA, which encodes the major cold-shock protein. Furthermore, RNase III cleaved overlapping 5′UTRs of divergently transcribed genes to generate leaderless mRNAs, which constitutes a novel way to co-regulate neighboring genes. In agreement with recent findings, low abundance antisense RNAs covering 44% of the annotated genes were captured by co-immunoprecipitation with RNase III mutant proteins. Thus, in addition to gene regulation, RNase III is associated with RNA quality control of pervasive transcription. Overall, this study illustrates the complexity of post-transcriptional regulation mediated by RNase III