Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience.

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach.

Should Koos grade I vestibular schwannomas be treated early with gamma knife surgery? A subgroup analysis in a series of 190 consecutive patients.

INTRODUCTION: Gamma knife surgery (GKS) for vestibular schwannomas (VS) has a long-term clinical and scientific track record. After a period of de-escalation of dose prescription, results show a high rate of tumor control with improvement of clinical outcome (less than 1% facial palsy, 50-70% hearing preservation). Régis et al. (J Neurosurg 2013;119 Suppl.:105-11) suggested recently that proactive GKS management in intracanalicular tumors is better than a « wait and see » strategy when hearing is still useful at the time of diagnosis. MATERIALS AND METHODS: Based on these previous findings, we prospectively analyzed 190 vestibular schwannomas (VS), treated with GKS as first intention over a period of 4 years (2010-2014). We concentrated on patient, tumor and dosimetric characteristics. Special attention was given on the dose to the cochlea and its impact in maintaining serviceable hearing. RESULTS: The mean follow-up period was 1.3years (range 0.6-3.6). Preoperative serviceable hearing was present in 63.11% patients. The mean maximal diameter was 15.1mm (range 5-29.5). The size and volume of the tumor corresponded to Koos grade I, II, III and IV in 15.9%, 34.8%, 45.4% and 3.8% of the cases, respectively. The mean target volume was 1.24cm(3) (0.017-7.8). The mean prescription isodose volume was 1.6 cc (0.032-8.5). The mean marginal dose was 12Gy (11-12). The mean maximal dose received by the cochlea in patients with GR class 1 and 2 was 4.1Gy (1.5-7.6). Our preliminary neuroradiological follow-up shows 97% tumor control, with 45% shrinkage. Patients presenting with GR class 1 and class 2 at baseline retained serviceable hearing in 85% of cases. Among the patients with a follow-up of at least one year, those with Koos I tumors had the highest probability to maintain identical level of hearing after GKS. CONCLUSION: Our preliminary data suggest that Koos I patients should be treated early with GKS, before tumor growth and/or hearing deterioration, as they have the highest probability of hearing preservation.

Variable queen number in ant colonies: no impact on queen turnover, inbreeding, and population genetic differentiation in the ant Formica selysi.

Variation in queen number alters the genetic structure of social insect colonies, which in turn affects patterns of kin-selected conflict and cooperation. Theory suggests that shifts from single- to multiple-queen colonies are often associated with other changes in the breeding system, such as higher queen turnover, more local mating, and restricted dispersal. These changes may restrict gene flow between the two types of colonies and it has been suggested that this might ultimately lead to sympatric speciation. We performed a detailed microsatellite analysis of a large population of the ant Formica selysi, which revealed extensive variation in social structure, with 71 colonies headed by a single queen and 41 by multiple queens. This polymorphism in social structure appeared stable over time, since little change in the number of queens per colony was detected over a five-year period. Apart from queen number, single- and multiple-queen colonies had very similar breeding systems. Queen turnover was absent or very low in both types of colonies. Single- and multiple-queen colonies exhibited very small but significant levels of inbreeding, which indicates a slight deviation from random mating at a local scale and suggests that a small proportion of queens mate with related males. For both types of colonies, there was very little genetic structuring above the level of the nest, with no sign of isolation by distance. These similarities in the breeding systems were associated with a complete lack of genetic differentiation between single- and multiple-queen colonies, which provides no support for the hypothesis that change in queen number leads to restricted gene flow between social forms. Overall, this study suggests that the higher rates of queen turnover, local mating, and population structuring that are often associated with multiple-queen colonies do not appear when single- and multiple-queen colonies still coexist within the same population, but build up over time in populations consisting mostly of multiple-queen colonies.

Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats.

Cocaine-induced neuroadaptation of stress-related circuitry and increased access to cocaine each putatively contribute to the transition from cocaine use to cocaine dependence. The present study tested the hypothesis that rats receiving extended versus brief daily access to cocaine would exhibit regional differences in levels of the stress-regulatory neuropeptide corticotropin-releasing factor (CRF). A secondary goal was to explore how CRF levels change in relation to the time since cocaine self-administration. Male Wistar rats acquired operant self-administration of cocaine and were assigned to receive daily long access (6 hours/day, LgA, n = 20) or short access (1 hour/day, ShA, n = 18) to intravenous cocaine self-administration (fixed ratio 1, ∼0.50 mg/kg/infusion). After at least 3 weeks, tissue CRF immunoreactivity was measured at one of three timepoints: pre-session, post-session or 3 hours post-session. LgA, but not ShA, rats showed increased total session and first-hour cocaine intake. CRF immunoreactivity increased within the dorsal raphe (DR) and basolateral, but not central, nucleus of the amygdala (BLA, CeA) of ShA rats from pre-session to 3 hours post-session. In LgA rats, CRF immunoreactivity increased from pre-session to 3 hours post-session within the CeA and DR but tended to decrease in the BLA. LgA rats showed higher CRF levels than ShA rats in the DR and, pre-session, in the BLA. Thus, voluntary cocaine intake engages stress-regulatory CRF systems of the DR and amygdala. Increased availability of cocaine promotes greater tissue CRF levels in these extrahypothalamic brain regions, changes associated here with a model of cocaine dependence.

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

A young man with a renal colic

We report the case of a 35-year-old man with no cardiovascular morbidity, presenting with acute flank pain, microscopic haematuria and normal blood pressure. Initially diagnosed as a ureteral colic, the patient was recovered 6 weeks later with severe hypertensive crisis. Further investigations revealed a massive renal infarction secondary to medial fibromuscular dysplasia (FMD). Several aspects of this presentation are intriguing. Renal infarcts are usually seen in older patients having cardiac problems and/or major atheromatous plaques. In addition, FMD is mainly observed in young females and rarely progresses to renal artery occlusion. Furthermore, in this case, FMD remained silent until the acute renal infarction occurred, despite a significant kidney size reduction at the time of diagnosis. Finally, the observation of a delayed hypertensive response to a major renovascular insult provides incentives to discuss possible pathophysiological mechanisms involved in renovascular hypertension.

Osteogenic sarcoma of the maxillary region in a Mexican mestizo population.

Background and Objectives: This study analyzed maxillary osteosarcoma in a mestizo population, with particular emphasis on the type of treatment and disease-free and overall survival. Methods: This is a retrospective study including all mestizo patients with osteosarcoma of the maxilla seen in a single cancer institution in Mexico during a 20-year period. Results: There were 21 patients. Age ranged from 16 to 76 years (mean, 37.5 y). Mean evolution time to diagnosis was 13 months, with a mean tumor size of 7 x 6 cm(2). Surgery was the initial treatment in 19 patients, 17 of whom received adjuvant treatment. Disease-free survival according to surgical margin and overall survival were not statistically significant. Disease-free survival was 29% at 5 years, and overall survival was 50% and 25% at 5 and 10 years, respectively. Conclusions: Osteosarcomas of the maxilla are infrequent lesions that merit early diagnosis and proper treatment because of their rapid evolution. Treatment is currently based on a well-planned surgery with free surgical margins plus adjuvant radiotherapy and/or chemotherapy.

Thrombocytosis as a prognostic marker in stage III and IV serous ovarian cancer.

OBJECTIVE: Thrombocytosis is an adverse prognostic factor in many types of cancer. We investigated if pre-treatment increased platelet counts provide prognostic information specifically in patients with stage III and IV serous ovarian cancer which is the most common clinical presentation of ovarian cancer. METHODS: Platelet number on diagnosis of stage III and IV serous ovarian adenocarcinoma was evaluated in 91 patients for whom there were complete follow-up data on progression and survival. Survival and progression free survival of patients with normal platelet counts (150-350 ×10(9)/L) was compared with that of patients with thrombocytosis (>350×10(9)/L) by χ(2) and logrank tests. RESULTS: The median age of the patients was 66 years-old. From the 91 patients, 52 (57.1%) had normal platelet counts (median, 273×10(9)/L; range, 153-350) at diagnosis of their disease and 39 patients (42.9%) had thrombocytosis (median, 463×10(9)/L; range, 354-631). In the group of patients with normal platelet counts, 24 of the 52 patients had died with a median survival of 43 months (range, 3-100). In the group of patients with thrombocytosis, 24 of the 39 patients had died with a median survival of 23 months (range, 4-79). In the entire group of 91 patients there was a statistically significant difference of the overall survival and progression-free survival between the two groups (logrank test P=0.02 and P=0.007, respectively). CONCLUSION: In this retrospective analysis of stage III and IV ovarian cancer patients, thrombocytosis at the time of diagnosis had prognostic value regarding overall survival and progression-free survival.

Prevalence and management of cardiovascular risk factors in Portuguese living in Portugal and Portuguese who migrated to Switzerland.

BACKGROUND: Information regarding the health status of migrants compared to subjects who remain in the country of origin is scarce. We compared the levels and management of the main cardiovascular risk factors between Portuguese living in Porto (Portugal) and Portuguese migrants living in Lausanne (Switzerland). METHODS: Cross-sectional studies conducted in Porto (EPIPorto, 1999 to 2003, n = 1150) and Lausanne (CoLaus, 2003 to 2006, n = 388) among subjects aged 35-65 years. Educational level, medical history and time since migration were collected using structured questionnaires. Body mass index, blood pressure, cholesterol and glucose levels were measured using standardized procedures. RESULTS: Portuguese living in Lausanne were younger, more frequently male and had lower education than Portuguese living in Porto. After multivariate adjustment using Poisson regression, no differences were found between Portuguese living in Porto or in Lausanne: prevalence rate ratio (PRR) and (95% confidence interval) for Portuguese living in Lausanne relative to Portuguese living in Porto: 0.92 (0.71 - 1.18) for current smoking; 0.78 (0.59 - 1.04) for obesity; 0.81 (0.62 - 1.05) for abdominal obesity; 0.82 (0.64 - 1.06) for hypertension; 0.88 (0.75 - 1.04) for hypercholesterolemia and 0.92 (0.49 - 1.73) for diabetes. Treatment and control rates for hypercholesterolemia were higher among Portuguese living in Lausanne: PRR = 1.91 (1.15 - 3.19) and 3.98 (1.59 - 9.99) for treatment and control, respectively. Conversely, no differences were found regarding hypertension treatment and control rates: PRR = 0.98 (0.66 - 1.46) and 0.97 (0.49 - 1.91), respectively, and for treatment rates of diabetes: PRR = 1.51 (0.70 - 3.25). CONCLUSIONS: Portuguese living in Lausanne, Switzerland, present a similar cardiovascular risk profile but tend to be better managed regarding hypercholesterolemia than Portuguese living in Porto, Portugal.

Clinical Utility of the 2 New Scales of the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA): A Naturalistic, Prospective Study in a Psychiatric Unit for Adolescents.

OBJECTIVES: The goal of this study was to assess the clinical usefulness of the emotional symptoms (Emo) and externalizing problems (Ext) scales compared with the Total score on the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). METHODS: The HoNOSCA was rated at admission and discharge for 260 adolescent inpatients. The primary outcomes assessed were (a) the sensitivity of the 3 HoNOSCA scores to clinical improvement; and (b) the between diagnoses discriminative value of these scores. RESULTS: Analyses of variances [2 (time: admission vs. discharge) ×5 (diagnostic groups)] revealed a main effect of time for the 3 scores, a main effect of the diagnostic group for the Total and Ext scores, and an interaction effect between time and diagnosis for the Emo score. A moderate correlation was observed between the change in Ext and Emo scores between admission and discharge. DISCUSSION: These 2 new scales of the HoNOSCA demonstrated good clinical utility and the ability to assess different aspects of clinical improvements. A significant discriminative value of both scores was observed. SIGNIFICANT OUTCOMES: The clinical utility of the 2 new scales on the HoNOSCA was established. These 2 new scales provided a sensitive measure of clinical outcome for assessing improvement between admission and discharge on a psychiatric inpatient unit for adolescents, regardless of diagnostic group, and captured additional information about clinical improvements. Adolescents with psychosis and conduct disorders presented with higher externalizing symptoms than those with other disorders, as rated on the HoNOSCA, at admission and discharge. The Emo score differentiated between clinical improvement in patients with psychosis versus eating disorders. LIMITATIONS: The sample in this study represented a homogeneous population of adolescent inpatients, so that further research is needed before these findings can be generalized to outpatients. In addition, the small number of patients in some diagnostic groups did not allow for their inclusion in some of the statistical analyses.

Prevalence and risk factors for therapy escalation in ulcerative colitis in the Swiss IBD Cohort Study

BACKGROUND: Physicians traditionally treat ulcerative colitis (UC) using a step-up approach. Given the paucity of data, we aimed to assess the cumulative probability of UC-related need for step-up therapy and to identify escalation-associated risk factors. METHODS: Patients with UC enrolled into the Swiss IBD Cohort Study were analyzed. The following steps from the bottom to the top of the therapeutic pyramid were examined: (1) 5-aminosalicylic acid and/or rectal corticosteroids, (2) systemic corticosteroids, (3) immunomodulators (IM) (azathioprine, 6-mercaptopurine, methotrexate), (4) TNF antagonists, (5) calcineurin inhibitors, and (6) colectomy. RESULTS: Data on 996 patients with UC with a median disease duration of 9 years were examined. The point estimates of cumulative use of different treatments at years 1, 5, 10, and 20 after UC diagnosis were 91%, 96%, 96%, and 97%, respectively, for 5-ASA and/or rectal corticosteroids, 63%, 69%, 72%, and 79%, respectively, for systemic corticosteroids, 43%, 57%, 59%, and 64%, respectively, for IM, 15%, 28%, and 35% (up to year 10 only), respectively, for TNF antagonists, 5%, 9%, 11%, and 12%, respectively, for calcineurin inhibitors, 1%, 5%, 9%, and 18%, respectively, for colectomy. The presence of extraintestinal manifestations and extended disease location (at least left-sided colitis) were identified as risk factors for step-up in therapy with systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and surgery. Cigarette smoking at diagnosis was protective against surgery. CONCLUSIONS: The presence of extraintestinal manifestations, left-sided colitis, and extensive colitis/pancolitis at the time of diagnosis were associated with use of systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and colectomy during the disease course.

Levyteollisuuden energia-, kustannus- ja ympäristövaikutukset

Kuluvien vuosien aikana ei ole tehty kattavia tutkimuksia levyteollisuuden sähkönkulutuksista, joten on aika selvittää suurimpien sähkökäyttöjen kulutukset sekä muodostaa tutkittaville tehtaille energiataseet. Tutkittavia tehtaita ovat OSB- ja lastulevytehtaat. Yksittäisten sähkömoottoreiden kulutukset saadaan selville käyttämällä hyväksi teoreettisia lähteitä, kenttä-ja laboratoriotutkimusta. Ympäristölainsäädäntö ja siihen kiinteästi liittyvä lupakäytäntö muodostavat levyteollisuudelle yhden viimeaikojen suurimmista haasteista. Tulevaisuudessa lainsäädäntö tulee vielä entisestäänkin kiristymään. Euroopan ympäristölainsäädäntö perustuu pitkälti yhtenäislupadirektiiviin eli IPPC-direktiiviin. Direktiivin keskeinen osa on ympäristöluvan hankkiminen, koska teollista toimintaa ei voi harjoittaa ilman hyväksyttyä viranomaisen lupaa. Lupa myös velvoittaa toiminnanharjoittajan käyttämään parasta käyttökelpoista tekniikkaa päästöjen kontrolloinnissa. Yhdysvalloissa parhaan käyttökelpoisen tekniikan (BAT) vaatimus on sisälletty ympäristövirasto EPA:n MACT-standardeihin. Levyteollisuuden tehtaista syntyvät päästöt ovat hyvin samankaltaisia. Tehtaista on helposti erotettavissa kaksi suurta päästölähdettä, joita ovat kuivaus ja kuumapuristus. Merkittävimpiä päästöjä ovat haihtuvat orgaaniset yhdisteet, hiukkaset, typen oksidit, hiilimonoksidi ja rikkidioksidit. Työn loppuosa on varattu tuotantojen kustannusvaikutusten ja tunnuslukujen tarkasteluille. Saatavilla tiedoilla on keskeinen rooli tehtaiden jokapäiväisessä toiminnassa. Analysoinnin tarpeeseen vaikuttaa osaltaan nykyisen toimintaympäristön muutosherkkyys ja levymarkkinoiden kireä kilpailutilanne.

Dynamic application development in Symbian OS

Diplomityössä tutkitaan, kuinka Symbian-sovelluskehitystä voitaisiin tehostaa. Työssä esitellään Symbian-käyttöjärjestelmä, sekä pohditaan haasteita ja rajoitteita joita Symbian sovelluskehityksessä kohdataan. Myöskin jo olemassa olevia kehitystapoja pohditaan työn tavoitteen kannalta. Symbian-sovelluskehityksessä tehdään toistuvasti samoja asioita. Koska Symbian on avoin käyttöjärjestelmä, sovelluskehittäjiä on paljon. Tehokkaamman kehitystavan löytäminen säästäisi paljon resursseja. Tällä hetkellä perinteiset ohjelmointitavat näyttävät olevan suosituin tapa kehittää sovelluksia. Kuitenkin on jo olemassa useita ratkaisuja, jotka pyrkivät tehostamaan sovelluskehitystä, mikä todistaa tarpeen kehittää tehokkuutta. Työssä toteutettu systeemi ajaa Symbian sovelluksia XML-määrityksen pohjalta. Kun käytetään XML-määritystä C++-koodin sijasta, sovelluskehitys muuttuu. Näiden muutosten täytyy kuitenkin olla myönteisiä, eivätkä ne saa haitata ohjelmiston laatua tai käytettävyyttä.

Characterization of volatile organic gunshot residues in fired handgun cartridges by headspace sorptive extraction

In forensic investigation of firearm-related cases, determination of the residual amount of volatile compounds remaining inside a cartridge could be useful in estimating the time since its discharge. Published approaches are based on following the decrease of selected target compounds as a function of time by using solid phase micro-extraction (SPME). Naphthalene, as well as an unidentified decomposition product of nitrocellulose (referred to as "TEA2"), are usually employed for this purpose. However, reliability can be brought into question given their high volatility and the low reproducibility of their extracted quantities. In order to identify alternatives and therefore develop improved dating methods, an extensive study on the composition and variability of volatile residues in nine different types of cartridges was carried out. Analysis was performed using headspace sorptive extraction (HSSE), which is a more exhaustive technique compared to SPME. 166 compounds were identified (several of which for the first time), and it was observed that the final compositional characteristics of each residue were strongly dependent on its source. Variability of single identified compounds within and between different types of cartridge, as well as their evolution over time, was also studied. Many explosion products containing up to 4 aromatic rings were found to be globally present in high proportions amongst residues. 27 of them (excluding naphthalene) also presented detectable decreases during the first 24 h. Therefore, they could be used as complementary target analytes in future dating methods.

Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis.

UNLABELLED: The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. INTRODUCTION: The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. METHODS: In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. RESULTS: Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS (p < 0.001). The predictive value of QUS was the same for men and women and for all ages (p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time (p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). CONCLUSIONS: Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values.