Use of GRADE for assessment of evidence about prognosis : rating confidence in estimates of event rates in broad categories of patients.

Main concepts : The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach defines quality of evidence as confidence in effect estimates; this conceptualization can readily be applied to bodies of evidence estimating the risk of future of events (that is, prognosis) in broadly defined populations In the field of prognosis, a body of observational evidence (including single arms of randomized controlled trials) begins as high quality evidence. The five domains GRADE considers in rating down confidence in estimates of treatment effect-that is, risk of bias, imprecision, inconsistency, indirectness, and publication bias-as well as the GRADE criteria for rating up quality, also apply to estimates of the risk of future of events from a body of prognostic studies Applying these concepts to systematic reviews of prognostic studies provides a ful approach to determine confidence in estimates of overall prognosis in broad populations.

Growth Models with Exogenous Saving Rates, Unemployment and Wage Inertia

[cat] El propòsit d'aquest article és introduir una mercat de treball no competitiu i atur en el model de creixement amb taxes d'estalvi exògenes que es pot trobar en els llibres de text de creixement (Sala‐i‐Martín, 2000; Barro and Sala‐i‐Martín, 2003; Romer, 2006). Primer, derivem un marc general amb una funció de producció neoclàssica per analitzar la relació entre creixement i ocupació. Utilitzem aquest marc per estudiar les dinàmiques conjuntes del creixement i l'ocupació sota diferents regles de fixació salarial.

Growth Models with Exogenous Saving Rates, Unemployment and Wage Inertia

[cat] El propòsit d'aquest article és introduir una mercat de treball no competitiu i atur en el model de creixement amb taxes d'estalvi exògenes que es pot trobar en els llibres de text de creixement (Sala‐i‐Martín, 2000; Barro and Sala‐i‐Martín, 2003; Romer, 2006). Primer, derivem un marc general amb una funció de producció neoclàssica per analitzar la relació entre creixement i ocupació. Utilitzem aquest marc per estudiar les dinàmiques conjuntes del creixement i l'ocupació sota diferents regles de fixació salarial.

Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells.

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the peptide-MHC (pMHC) on cells is a key parameter for cell-mediated immunity. Yet a fundamental feature of most tumor antigen-specific CD8(+) T cells is that this avidity is low. In this study, we addressed the need to identify and select tumor-specific CD8(+) T cells of highest avidity, which are of the greatest interest for adoptive cell therapy in patients with cancer. To identify these rare cells, we developed a peptide-MHC multimer technology, which uses reversible Ni(2+)-nitrilotriacetic acid histidine tags (NTAmers). NTAmers are highly stable but upon imidazole addition, they decay rapidly to pMHC monomers, allowing flow-cytometric-based measurements of monomeric TCR-pMHC dissociation rates of living CD8(+) T cells on a wide avidity spectrum. We documented strong correlations between NTAmer kinetic results and those obtained by surface plasmon resonance. Using NTAmers that were deficient for CD8 binding to pMHC, we found that CD8 itself stabilized the TCR-pMHC complex, prolonging the dissociation half-life several fold. Notably, our NTAmer technology accurately predicted the function of large panels of tumor-specific T cells that were isolated prospectively from patients with cancer. Overall, our results demonstrated that NTAmers are effective tools to isolate rare high-avidity cytotoxic T cells from patients for use in adoptive therapies for cancer treatment.

Annonaceae substitution rates: a codon model perspective

The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these differences has led to inconsistent results when estimating the ages of clades in Annonaceae using molecular dating techniques. We ask whether these differences may be attributed to inappropriate modelling assumptions in the phylogenetic analyses. Specifically, we test for (clade-specific) differences in rates of non-synonymous and synonymous substitutions. A high ratio of nonsynonymous to synonymous substitutions may lead to similarity of DNA sequences due to convergence instead of common ancestry, and as a result confound phylogenetic analyses. We use a dataset of three chloroplast genes (rbcL, matK, ndhF) for 129 species representative of the family. We find that differences in branch lengths between major clades are not attributable to different rates of non-synonymous and synonymous substitutions. The differences in evolutionary rate between the major clades of Annonaceae pose a challenge for current molecular dating techniques that should be seen as a warning for the interpretation of such results in other organisms.

Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

Participation rates for organized colorectal cancer screening programmes: an international comparison.

OBJECTIVE: Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. METHODS: Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. RESULTS: Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30-100%, coverage by the screening programme from 7-67.7%, overall uptake/participation rate from 7-67.7%, and first invitation participation from 7-64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. CONCLUSION: Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously.

Railway Wagon Market Analysis and New Multi-Purpose Wagon Solution for Freight Transports - Finnish Manufacturing Perspective

Rautateillä käytettävät tavaravaunut ovat vanhenemassa hyvin nopeasti; tämä koskee niin Venäjää, Suomea, Ruotsia kuin laajemminkin Eurooppaa. Venäjällä ja Euroopassa on käytössä runsaasti vaunuja, jotka ovat jo ylittäneet niille suositeltavan käyttöiän. Silti niitä käytetään kuljetuksissa, kun näitä korvaavia uusia vaunuja ei ole tarpeeksi saatavilla. Uusimmat vaunut ovat yleensä vaunuja vuokraavien yritysten tai uusien rautatieoperaattorien hankkimia - tämä koskee erityisesti Venäjää, jossa vaunuvuokraus on noussut erittäin suosituksi vaihtoehdoksi. Ennusteissa kerrotaan vaunupulan kasvavan ainakin vuoteen 2010 saakka. Jos rautateiden suosio rahtikuljetusmuotona kasvaa, niin voimistuva vaunukysyntä jatkuu huomattavan paljon pidemmän aikaa. Euroopan ja Venäjän vaunukannan tilanne näkyy myös sitä palvelevan konepajateollisuuden ongelmina - yleisesti ottaen alan eurooppalaiset yritykset ovat heikosti kannattavia ja niiden liikevaihto ei juuri kasva, venäläiset ja ukrainalaiset yritykset ovat olleet samassa tilanteessa, joskin aivan viime vuosina tilanne on osassa kääntynyt paremmaksi. Kun näiden maanosien yritysten liikevaihtoa, voittoa ja omistaja-arvoa verrataan yhdysvaltalaisiin kilpailijoihin, huomataan että jälkimmäisten suoriutuminen on huomattavan paljon parempaa, ja näillä yrityksillä on myös kyky maksaa osinkoja omistajilleen. Tutkimuksen tarkoituksena oli kehittää uuden tyyppinen kuljetusvaunu Suomen, Venäjän sekä mahdollisesti myös Kiinan väliseen liikenteeseen. Vaunutyypin tarkoituksena olisi kyetä toimimaan monikäyttöisenä, niin raaka-aineiden kuin konttienkin kuljetuksessa, tasapainottaen kuljetusmuotojen aiheuttamaa kuljetuspaino-ongelmaa. Kehitystyön pohjana käytimme yli 1000 venäläisen vaunutyypin tietokantaa, josta valitsimme Data Envelopment Analysis -menetelmällä soveliaimmat vaunut kontinkuljetukseen (lähemmin tarkastelimme n. 40 vaunutyyppiä), jättäen mahdollisimman vähän tyhjää tilaa junaan, mutta silti kyeten kantamaan valitun konttilastin. Kun kantokykyongelmia venäläisissä vaunuissa ei useinkaan ole, on vertailu tehtävissä tavarajunan pituuden ja kokonaispainon perusteella. Simuloituamme yhdistettyihin kuljetuksiin soveliasta vaunutyyppiä käytännössä löytyvässä kuljetusverkostossa (esim. raakapuuta Suomeen tai Kiinaan ja kontteja takaisin Venäjän suuntaan), huomasimme lyhemmän vaunupituuden sisältävän kustannusetua, erityisesti raakaainekuljetuksissa, mutta myös rajanylityspaikkojen mahdollisesti vähentyessä. Lyhempi vaunutyyppi on myös joustavampi erilaisten konttipituuksien suhteen (40 jalan kontin käyttö on yleistynyt viime vuosina). Työn lopuksi ehdotamme uuden vaunutyypin tuotantotavaksi verkostomaista lähestymistapaa, jossa osa vaunusta tehtäisiin Suomessa ja osa Venäjällä ja/tai Ukrainassa. Vaunutyypin tulisi olla rekisteröity Venäjälle, sillä silloin sitä voi käyttää Suomen ja Venäjän, kuten myös soveltuvin osin Venäjän ja Kiinan välisessä liikenteessä.

High rates of smoking especially in female Crohn's disease patients and low use of supportive measures to achieve smoking cessation : Data from the SwissIBD cohort study

BACKGROUND AND AIMS: Smoking is a crucial environmental factor in inflammatory bowel disease (IBD). However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. METHODS: Prospectively obtained data from patients participating in the Swiss IBD cohort study was analysed and compared to the general Swiss population (GSP) matched by age, sex and year. RESULTS: Among a total of 1770 IBD patients analysed (49.1% male), 29% are current smokers. More than twice as many patients with Crohn's disease (CD) are active smokers compared to ulcerative colitis (UC, 39.6% vs. 15.3%, p<0.001). In striking contrast to the GSP, significantly more women than men with CD smoke (42.8% vs. 35.8%, p=0.025), with also an overall significantly increased smoking rate compared to the GSP in women but not men. The vast majority of smoking IBD patients (90.5%) claim to never have received any support to achieve smoking cessation, significantly more in UC compared to CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared to non-smokers, but does not differ in UC CONCLUSIONS: Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared to the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation.

Impact of a Dedicated Noninvasive Ventilation Team on Intubation and Mortality Rates in Severe COPD Exacerbations.

BACKGROUND: Compared with usual care, noninvasive ventilation (NIV) lowers the risk of intubation and death for subjects with respiratory failure secondary to COPD exacerbations, but whether administration of NIV by a specialized, dedicated team improves its efficiency remains uncertain. Our aim was to test whether a dedicated team of respiratory therapists applying all acute NIV treatments would reduce the risk of intubation or death for subjects with COPD admitted for respiratory failure. METHODS: We carried out a retrospective study comparing subjects with COPD admitted to the ICU before (2001-2003) and after (2010-2012) the creation of a dedicated NIV team in a regional acute care hospital. The primary outcome was the risk of intubation or death. The secondary outcomes were the individual components of the primary outcome and ICU/hospital stay. RESULTS: A total of 126 subjects were included: 53 in the first cohort and 73 in the second. There was no significant difference in the demographic characteristics and severity of respiratory failure. Fifteen subjects (28.3%) died or had to undergo tracheal intubation in the first cohort, and only 10 subjects (13.7%) in the second cohort (odds ratio 0.40, 95% CI 0.16-0.99, P = .04). In-hospital mortality (15.1% vs 4.1%, P = .03) and median stay (ICU: 3.1 vs 1.9 d, P = .04; hospital: 11.5 vs 9.6 d, P = .04) were significantly lower in the second cohort, and a trend for a lower intubation risk was observed (20.8% vs 11% P = .13). CONCLUSIONS: The delivery of NIV by a dedicated team was associated with a lower risk of death or intubation in subjects with respiratory failure secondary to COPD exacerbations. Therefore, the implementation of a team administering all NIV treatments on a 24-h basis should be considered in institutions admitting subjects with COPD exacerbations.

Developing service offering of an air freight carrier

The thesis examined service offering development of an air freight carrier from the customers' point of view. The study was limited to the biggest business clients of the carrier. Service offering development can be divided into service concept, process and system. The thesis was based on these three themes and quality. Compared to product development, systematic and well-structured service development has been studied little, especially in business market. However, service development is a current issue. Due to growing competition companies should carefully listen to their clients' needs and respond to them by offering right services. Methodology of the thesis is qualitative and representatives of three forwarding companies were interviewed. It was found out that the forwarding companies consider themselves as partners of the airline. In addition to general reliability, the customers value the most fluent terminal processes and electronic communication.