ß-Spectrin São PauloII, a novel frameshift mutation of the ß-spectrin gene associated with hereditary spherocytosis and instability of the mutant mRNA

Hereditary spherocytosis (HS) is a common inherited anemia characterized by the presence of spherocytic red cells. Defects in several membrane protein genes have been involved in the pathogenesis of HS. ß-Spectrin-related HS seems to be common. We report here a new mutation in the ß-spectrin gene coding region in a patient with hereditary spherocytosis. The patient presented acanthocytosis and spectrin deficiency and, at the DNA level, a novel frameshift mutation leading to HS, i.e., a C deletion at codon 1392 (ß-spectrin São PauloII), exon 20. The mRNA encoding ß-spectrin São PauloII was very unstable and the mutant protein was not detected in the membrane or in other cellular compartments. It is interesting to note that frameshift mutations of the ß-spectrin gene at the 3' end allow the insertion of the mutant protein in the red cell membrane, leading to a defect in the auto-association of the spectrin dimers and consequent elliptocytosis. On the other hand, ß-spectrin São PauloII protein was absent in the red cell membrane, leading to spectrin deficiency, HS and the presence of acanthocytes.

Work and non-work : on work and meaning

I den politiska retoriken florerar debattinlägg om arbetslivet, och målsättningen är för det mesta att så många som möjligt ska arbeta så länge som möjligt. Att skapa jobb och minimera arbetslösheten ses som de främsta utmaningarna. På ett individuellt plan beskrivs arbete ofta som personligt självförverkligande eller som en nödvändig form av inkomst som kräver att livet struktureras enligt behovet av sysselsättning. I avhandlingen diskuteras hur de här till synes självklara rollerna som arbete spelar kan sägas neutralisera arbete. Med detta menas att kontroverser kring arbetets mening åsidosätts så att politiskt och etiskt grundläggande frågor om ett gott liv och mänskliga gemenskaper inte ges plats. Genom att gå i dialog med kritiska tänkare som Hannah Arendt, André Gorz, Kathi Weeks, Karl Marx och Richard Sennett diskuteras riskerna med att behandla arbete som en resurs, ett gemensamt samhällsprojekt eller individuellt självförverkligande. Vad är nödvändigt arbete? Vad innebär det att arbete är en vara? Vad är problemet med fragmentering av arbete? Det sägs ofta att arbete har blivit alltmer gränslöst – är detta något positivt eller negativt? Utifrån sådana frågor tar avhandlingen fasta på spänningar i arbetets roll i våra liv och i samhället. Genom att artikulera spänningar utmanas en neutralisering av arbetets etiskt och politiskt brännbara dimensioner. Avhandlingen syftar därmed till att lyfta fram ständigt pågående sätt att ifrågasätta och reflektera kring arbetets mening.

How computer programmers work : understanding software development in practise

Hur arbetar en framgångsrik programmerare? Uppgifterna att programmera datorspel och att programmera industriella, säkerhetskritiska system verkar tämligen olika. Genom en noggrann empirisk undersökning jämför och kontrasterar avhandlingen dessa två former av programmering och visar att programmering innefattar mer än teknisk förmåga. Med utgångspunkt i hermeneutisk och retorisk teori och med hjälp av både kulturvetenskap och datavetenskap visar avhandlingen att programmerarnas tradition och värderingar är grundläggande för deras arbete, och att båda sorter av programmering kan uppfattas och analyseras genom klassisk texttolkningstradition. Dessutom kan datorprogram betraktas och analyseras med hjälp av klassiska teorier om talproduktion i praktiken - program ses då i detta sammanhang som ett slags yttranden. Allt som allt förespråkar avhandlingen en återkomst till vetenskapens grunder, vilka innebär en ständig och oupphörlig cyklisk rörelse mellan att erfara och att förstå. Detta står i kontrast till en reduktionistisk syn på vetenskapen, som skiljer skarpt mellan subjektivt och objektivt, och på så sätt utgår från möjligheten att uppnå fullständigt vetande. Ofullständigt vetande är tolkandets och hermeneutikens domän. Syftet med avhandlingen är att med hjälp av exempel demonstrera programmeringens kulturella, hermeneutiska och retoriska natur.

Delta sleep instability in children with chronic arthritis

The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 ± 6.7 vs 95.8 ± 4.0), sleep stage in minutes: stage 1 (16.8 ± 8.5 vs 17.8 ± 4.0), stage 2 (251.9 ± 41 vs 262.8 ± 38.1), stage 3 (17.0 ± 6.0 vs 15.1 ± 5.7), stage 4 (61.0 ± 21.7 vs 77.1 ± 20.4), and rapid eye movement sleep (82.0 ± 27.6 vs 99.0 ± 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

Sleep, ageing and night work

Studies have shown that the frequency or worsening of sleep disorders tends to increase with age and that the ability to perform circadian adjustments tends to decrease in individuals who work the night shift. This condition can cause consequences such as excessive sleepiness, which are often a factor in accidents that occur at work. The present study investigated the effects of age on the daytime and nighttime sleep patterns using polysomnography (PSG) of long-haul bus drivers working fixed night or day shifts. A total of 124 drivers, free of sleep disorders and grouped according to age (<45 years, N = 85, and ≥45 years, N = 39) and PSG timing (daytime (D) PSG, N = 60; nighttime (N) PSG, N = 64) participated in the study. We observed a significant effect of bedtime (D vs N) and found that the length of daytime sleep was shorter [D: <45 years (336.10 ± 73.75 min) vs N: <45 years (398 ± 78.79 min) and D: ≥45 years (346.57 ± 43.17 min) vs N: ≥45 years (386.44 ± 52.92 min); P ≤ 0.05]. Daytime sleep was less efficient compared to nighttime sleep [D: <45 years (78.86 ± 13.30%) vs N: <45 years (86.45 ± 9.77%) and D: ≥45 years (79.89 ± 9.45%) and N: ≥45 years (83.13 ± 9.13%); P ≤ 0.05]. An effect of age was observed for rapid eye movement sleep [D: <45 years (18.05 ± 6.12%) vs D: ≥45 years (15.48 ± 7.11%) and N: <45 years (23.88 ± 6.75%) vs N: ≥45 years (20.77 ± 5.64%); P ≤ 0.05], which was greater in younger drivers. These findings are inconsistent with the notion that older night workers are more adversely affected than younger night workers by the challenge of attempting to rest during the day.

Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise

We determined the response characteristics and functional correlates of the dynamic relationship between the rate (Δ) of oxygen consumption ( O2) and the applied power output (work rate = WR) during ramp-incremental exercise in patients with mitochondrial myopathy (MM). Fourteen patients (7 males, age 35.4 ± 10.8 years) with biopsy-proven MM and 10 sedentary controls (6 males, age 29.0 ± 7.8 years) took a ramp-incremental cycle ergometer test for the determination of the O2 on-exercise mean response time (MRT) and the gas exchange threshold (GET). The ΔO2/ΔWR slope was calculated up to GET (S1), above GET (S2) and over the entire linear portion of the response (S T). Knee muscle endurance was measured by isokinetic dynamometry. As expected, peak O2 and muscle performance were lower in patients than controls (P < 0.05). Patients had significantly lower ΔO2/ΔWR than controls, especially the S2 component (6.8 ± 1.5 vs 10.3 ± 0.6 mL·min-1·W-1, respectively; P < 0.001). There were significant relationships between ΔO2/ΔWR (S T) and muscle endurance, MRT-O2, GET and peak O2 in MM patients (P < 0.05). In fact, all patients with ΔO2/ΔWR below 8 mL·min-1·W-1 had severely reduced peak O2 values (<60% predicted). Moreover, patients with higher cardiopulmonary stresses during exercise (e.g., higher Δ ventilation/carbon dioxide output and Δ heart rate/ΔO2) had lower ΔO2/ΔWR (P < 0.05). In conclusion, a readily available, effort-independent index of aerobic dysfunction during dynamic exercise (ΔO2/ΔWR) is typically reduced in patients with MM, being related to increased functional impairment and higher cardiopulmonary stress.

Dynamics of chest wall volume regulation during constant work rate exercise in patients with chronic obstructive pulmonary disease

This study evaluated the dynamic behavior of total and compartmental chest wall volumes [(V CW) = rib cage (V RC) + abdomen (V AB)] as measured breath-by-breath by optoelectronic plethysmography during constant-load exercise in patients with stable chronic obstructive pulmonary disease. Thirty males (GOLD stages II-III) underwent a cardiopulmonary exercise test to the limit of tolerance (Tlim) at 75% of peak work rate on an electronically braked cycle ergometer. Exercise-induced dynamic hyperinflation was considered to be present when end-expiratory (EE) V CW increased in relation to resting values. There was a noticeable heterogeneity in the patterns of V CW regulation as EEV CW increased non-linearly in 17/30 "hyperinflators" and decreased in 13/30 "non-hyperinflators" (P < 0.05). EEV AB decreased slightly in 8 of the "hyperinflators", thereby reducing and slowing the rate of increase in end-inspiratory (EI) V CW (P < 0.05). In contrast, decreases in EEV CW in the "non-hyperinflators" were due to the combination of stable EEV RC with marked reductions in EEV AB. These patients showed lower EIV CW and end-exercise dyspnea scores but longer Tlim than their counterparts (P < 0.05). Dyspnea increased and Tlim decreased non-linearly with a faster rate of increase in EIV CW regardless of the presence or absence of dynamic hyperinflation (P < 0.001). However, no significant between-group differences were observed in metabolic, pulmonary gas exchange and cardiovascular responses to exercise. Chest wall volumes are continuously regulated during exercise in order to postpone (or even avoid) their migration to higher operating volumes in patients with COPD, a dynamic process that is strongly dependent on the behavior of the abdominal compartment.

Disentangling the effects of insomnia and night work on cardiovascular diseases: a study in nursing professionals

Cardiovascular diseases (CVDs) are known to be associated with poor sleep quality in general populations, but they have not been consistently associated with specific work schedules. Studies of CVD generally do not simultaneously consider sleep and work schedules, but that approach could help to disentangle their effects. We investigated the association between insomnia and a self-reported physician diagnosis of CVD in day and night workers, considering all sleep episodes during nocturnal and diurnal sleep. A cross-sectional study was conducted in 1307 female nursing professionals from 3 public hospitals, using baseline data from the “Health and Work in Nursing - a Cohort Study.” Participants were divided into two groups: i) day workers with no previous experience in night shifts (n=281) and whose data on insomnia were related to nocturnal sleep and ii) those who worked exclusively at night (n=340) and had data on both nocturnal and diurnal sleep episodes, as they often sleep at daytime. Multiple logistic regression analysis was performed. Among day workers, insomnia complaints increased the odds of CVD 2.79-fold (95% CI=1.01-6.71) compared with workers who had no complaints. Among night workers, reports of insomnia during both nocturnal and diurnal sleep increased the odds of reported CVD 3.07-fold (95% CI=1.30-7.24). Workers with insomnia had similar probabilities of reporting CVD regardless of their work schedule, suggesting a relationship to insomnia and not to night work per se. The results also highlighted the importance of including evaluation of all sleep episodes (diurnal plus nocturnal sleep) for night workers.

Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Thoughts on work-in-progress crowdsourcing metrics of digital collections

The presentation consists of work-in-progress metrics of #digitalkoot, the crowdsourcing project launched by National Library of Finland

Designing gamification for collaborative learning in group work

Computer Supported Collaborative Learning (CSCL) is a teaching and learning approach which is widely adopted. However there are still some problems can be found when CSCL takes place. Studies show that using game-like mechanics can increase motivation, engagement, as well as modelling behaviors of players. Gamification is a rapid growing trend by applying the same mechanics. It refers to use game design elements in non-game contexts. This thesis is about combining gamification concept and computer supported collaborative learning together in software engineering education field. And finally a gamified prototype system is designed.

TYÖILMOITUS TYÖNANTAJALUPAUKSIEN JA TYÖARVOJEN VIESTIJÄNÄ Tarkastelussa menestyneitä Great Place to Work -työnantajia

Työilmoitus voi jäädä työnhakijan ja työnantajan välillä ainoaksi viestinnän mahdollisuudeksi, jolloin ratkaisevaa on, kuinka houkuttelevaksi työnantaja työilmoituksensa laatii kilpaillessaan halutuista osaajista. Samalla työilmoitus antaa lupauksia tulevasta työstä ja työyhteisöstä. Tämän tutkimuksen perimmäinen tarkoitus on tutkia, näkyykö työsuhteen kahdenvälinen transaktioluonne työilmoitusten tasolla eli kerrotaanko ilmoituksissa työnantajan osaajatarpeiden lisäksi, mitkä olisivat työntekijän työllistymisellä saavutetut hyödyt. Tarkemmiksi tarkastelun kohteiksi on valittu kaksi työnhakijan päätöksenteon kannalta mielenkiintoista näkökulmaa: viestityt työarvot ja työnantajalupaukset. Teoreettiselta taustaltaan tämä tutkimus liittyy rekrytoinnin kokonaisuuteen, mutta se sivuaa useita muita aihealueita, kuten yksilön ja yrityksen yhteensopivuutta, työnantajamielikuvaa, psykologista sopimusta, informaation prosessointia, suostuttelua ja työnhakupäätöksen syntymekanismin tutkimusta. Tutkimuksen empiirinen aineisto koostuu kolmena peräkkäisenä vuonna (2013−2015) Suomen parhaimmiksi työnantajiksi tituleerattujen yritysten julkaisemista työilmoituksista. Näiden oletettiin olevan kiinnostuneita työnantajakuvastaan ja rekrytoinnistaan keskimääräistä enemmän. Kerätyistä 19 työilmoituksesta tulkittiin arvoilmaisuja ja annettuja esilupauksia kahden teoreettisen luokituksen yhdistelmänä muodostetun analyysirungon avulla. Aineiston lauseita eriteltiin analyysirungon teemojen alle ja niiden vakuuttamiskeinoja analysoitiin retorisella diskurssianalyysillä. Tutkimuksen tuloksena havaittiin, että työnteon puitteista, palkkatiedoista, määräysvallasta ja työn merkityksellisyydestä mainittiin verrattain vähän työilmoituksissa. Sen sijaan aineiston työilmoituksista löytyi runsaasti ilmaisuja, joista työnhakija voi tehdä päätelmiä työilmapiiristä tai potentiaalisten kollegoiden asiantuntijuuden tasosta. Yrittäjähenkisyys- ja suorituspainepuheiden läpi heijastui puolestaan kovemmat arvot. Arvojen ilmaisu tapahtui usein epäsuorasti kuin selkeinä arvolistoina. Konkreettisia lupauksia työnantajalta työnhakijalle tehtiin vähän tai ne olivat ylimalkaisia. Tutkimus antaa aihetta laajemmille kartoituksille. Mitkä ovat syyt tiettyä kaavaa toistavien työilmoitusten taustalla ja mitkä tekijät työilmoituksissa eri kohdeyleisöjä aidosti vaikuttavat?