On The Time Scale of Internal Energy Relaxation of AP-MALDI and nano-ESI Ions in a Quadrupole Ion Trap

Recently reported results (Konn et al. [14]) on the collisional cooling of atmospheric pressure matrix assisted laser desorption ionization (AP-MALDI) and nano-electrospray ionization (nano-ESI) generated ions in a quadrupole ion trap mass spectrometer (QITMS) are inconsistent with measured collisional cooling rates. The work reported here presents a re-examination of those previous results. Collision induced dissociation (CID) has been used to probe various properties of ions contained in a QITMS. It is shown experimentally that when trapping large numbers of ions, an effective dc trapping voltage is induced that varies with changes in the size of the ion cloud. A decrease in the resonant frequency for maximum CID efficiency is observed as the cool time between parent ion isolation and CID is increased. Ion trajectories in a QITMS are simulated to demonstrate how ion density changes over the course of parent ion isolation. The effect of space charge on ion motion is simulated, and Fourier transformations of ion axial motion plus simple calculations corroborate the experimentally observed transient frequency shifts. The relative stability of ions formed by AP-MALDI and nano-ESI is compared under low charge density conditions. These data show that the ions have reached equilibrium internal energy and, thus, that differences in dissociation onsets and “50% fragmentation efficiency points” between the ionization mechanisms are due to the formation of distinct ion conformations as previously shown in reference [28]. The conclusions of Konn et al. [14] are based on invalid experimental procedures as well as inappropriate comparisons of QITMS data to low-pressure FT-ICR data

Comparing human and automatic speech recognition in a perceptual restoration experiment

Speech that has been distorted by introducing spectral or temporal gaps is still perceived as continuous and complete by human listeners, so long as the gaps are filled with additive noise of sufficient intensity. When such perceptual restoration occurs, the speech is also more intelligible compared to the case in which noise has not been added in the gaps. This observation has motivated so-called 'missing data' systems for automatic speech recognition (ASR), but there have been few attempts to determine whether such systems are a good model of perceptual restoration in human listeners. Accordingly, the current paper evaluates missing data ASR in a perceptual restoration task. We evaluated two systems that use a new approach to bounded marginalisation in the cepstral domain, and a bounded conditional mean imputation method. Both methods model available speech information as a clean-speech posterior distribution that is subsequently passed to an ASR system. The proposed missing data ASR systems were evaluated using distorted speech, in which spectro-temporal gaps were optionally filled with additive noise. Speech recognition performance of the proposed systems was compared against a baseline ASR system, and with human speech recognition performance on the same task. We conclude that missing data methods improve speech recognition performance in a manner that is consistent with perceptual restoration in human listeners

Immunohistochemical Expression of Somatostatin Receptor Subtypes in a Panel of Neuroendocrine Neoplasias

Neuroendocrine neoplasias (NENs) are known to express somatostatin receptors (SSTRs) 1-5, which are G-protein-coupled cell membrane receptors. Somatostatin receptor imaging and therapy utilizes the SSTR expression. Synthetic somatostatin analogs with radioligands are used to detect primary tumors, metastases, and recurrent disease. Receptor analogs are also used for treating NENs. Furthermore, commercially available SSTR antibodies can be used for the immunohistochemical (IHC) detection of SSTRs. We investigated different SSTR antibody clones applying diverse IHC protocol settings to identify reliable clones and feasible protocols for NENs. A tissue microarray including NENs from 12 different primary sites were stained. Only UMB clones were able to localize SSTR on the cell membranes of NENs. SSTR2 (UMB1) emerged as the most common subtype followed by SSTR5 (UMB4) and SSTR1 (UMB7). SSTR3 (UMB5) expression was mainly cytoplasmic. Yet, SSTR4 expression was weak and located primarily in the cytoplasm. Thus, appropriate IHC protocols, including proper positive and negative controls, represent requirements for high-quality NEN diagnostics and for planning personalized therapy.Peer reviewe

Does early drug use-related police contact predict premature mortality and morbidity : A population register-based study

Introduction The aim was to analyse whether age at first drug offense predicts premature mortality and morbidity due to substance use and violence among adolescents and young adults. Methods A prospective longitudinal register-linkage study based on a total population sample from Finland including individuals born between 1987 and 1992 and aged 15-25 years during follow-up in 2002-2017 (n = 386 435). Age-specific rates of deaths and health-care admissions (morbidity) during a 5-year follow-up were calculated from the first drug offense. Cox regression models were used to estimate differences in mortality and morbidity at ages 21-25. Results Of all 15- to 20-year-olds, 1.4% (n = 5540) have had a police contact. The 5-year mortality rates (per 1000 person-years) among those with first drug offense at ages 15-16 was 2.92 [95% confidence interval (CI) 1.56-6.18], and 5.26 (CI 4.00-7.07) and 5.05 (CI 4.06-6.38) at ages 17-18, and 19-20, respectively. The rates of morbidity varied between 61.20 (CI 52.43-71.76) and 87.51 (CI 82.11-93.33). Both mortality and morbidity rates were over 10 times higher than among the general population. In models adjusted for family background, first police contact at an early age (15-16) did not increase the risk of mortality at ages 21-25 compared with first police contact at ages 17-18 (hazard ratio 1.55, CI 0.77-3.09) or 19-20 (hazard ratio 1.52, CI 0.78-2.98). The results were similar for morbidity. Discussion and Conclusions Adolescents with drug-related police contacts have high risk of mortality and morbidity due to substance use and violence regardless of age of first contact.Peer reviewe

Abundance and Species Richness of Leafhoppers and Planthoppers (Hemiptera: Cicadellidae and Delphacidae) in Brazilian Maize Crops

Fil: De Oliveira, Charles Martins. Embrapa Cerrados. Planaltina. Brasília/DF; BrazilFil: De Oliveira, Elizabeth. Embrapa Milho e Sorgo. Sete Lagoas/MG; BrazilFil: Prazeres De Souza, Isabel Regina. Embrapa Milho e Sorgo. Sete Lagoas/MG; BrazilFil: Alves, Elcio. DuPont do Brazil S.A. DivisÆo Pioneer Sementes. Itumbiara/GO; BrazilFil: Dolezal, William. Pioneer Hi-Bred International. Itumbiara/GO; BrazilFil: Paradell, Susana Liria. División Entomología. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Marino de Remes Lenicov, Ana María. División Entomología. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Frizzas, Marina Regina. Universidade de Brasília. Departamento de Zoologia. Instituto de Ciências Biológicas. Brasília/DF; Brazi

Long-lasting obesity predicts poor work ability at midlife: a 15-year follow-up of the northern Finland 1966 birth cohort study

Objective: To investigate the effect of adulthood obesity on work ability in early midlife during a 15-year follow-up. Methods: The study population included men and women (n = 5470), born in northern Finland in 1966. Participants evaluated their current perceived work ability compared with their lifetime best at the age of 46. Participants’ weight and height were measured at 31 years and self-reported at 46 years, and body mass indexes were calculated. Results: Obesity at both ages, and developing obesity between the ages of 31 and 46 increased the relative risk of poor work ability at 46 years among sexes, and among those in both low and high physically strenuous work. Conclusions: Long-term obesity and developing obesity in mid-adulthood increase the risk of poor work ability. Thus, the promotion of healthy behaviors by policies, healthcare services, and at workplaces is important

Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients

Shoulder Capsular Surgery in Finland Between 1999 and 2008 : A Nationwide Register Analysis

Background and Aims: Shoulder capsular surgery is nowadays usually performed arthroscopically, and the proportion of arthroscopic method has rapidly increased during the last two decades. We assessed the incidence of shoulder capsular surgery procedures in Finland between 1999 and 2008. Material and Methods: We gathered the shoulder capsular surgery procedures for all kinds of shoulder instability in Finland between 1999 and 2008 from National Hospital Discharge Register and limited the patient material to include only certain diagnosis (International Classification of Diseases, 10th Edition) and Nordic Medico-Statistical Committee procedure code combinations. We analyzed the data in the whole country, between different age groups, and in university hospital districts. Results: The total incidence of shoulder capsular surgery procedures in Finland increased from 17 to 33 per 100,000 person-years. The incidence of arthroscopic procedures increased from 11 to 30 per 100,000 person-years and the proportion of arthroscopic procedures increased from 63% to 92% between years 1999 and 2007. The incidence of shoulder capsular surgery procedures increased on average around 90% in almost all age groups and particularly in the older age groups. We observed no significant geographical variation between university hospital districts. Conclusion: The incidence of shoulder capsular surgery procedures increased on average round 90% in almost all age groups. It seems to be difficult to support the rapidly increased rates of shoulder capsular surgery procedures or the arthroscopic method based on scientific evidence. While also older patients are treated with shoulder capsular surgery, well-defined indications for surgical intervention are needed so that the operations are conducted for the symptomatic patients benefitting most regardless of patients' age.Peer reviewe

Sex differences in the association between area deprivation and generalised anxiety disorder: British population study

OBJECTIVE Studies have shown that area-level deprivation measured by factors, such as, non-home ownership, non-car ownership, and household overcrowding, can increase the risk for mental disorders over and above individual-level circumstances, such as, education and social class. Whether area-level deprivation is associated with generalised anxiety disorder independent of personal circumstances, and whether this association is different between British women and men is unknown. DESIGN Large, population study. SETTING UK population-based cohort. PARTICIPANTS 30,445 people from the general population aged 40 years and older and living in England consented to participate at study baseline, and of these, 21,000 participants completed a structured health and lifestyle questionnaire used to capture generalised anxiety disorder. Area deprivation was measured in 1991 using Census data, and generalised anxiety disorder was assessed in 1996-2000. 10,275 women and 8,219 men had complete data on all covariates. MAIN OUTCOME MEASURE Past-year generalised anxiety disorder defined according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). RESULTS In this study, 2.5% (261/10,275) of women and 1.8% (145/8,219) of men had generalised anxiety disorder. Women living in the most deprived areas were over 60% more likely to develop anxiety than those living in areas that were not deprived (OR=1.63, 95%CI: 1.21 to 2.21; p=0.001), but this association between deprivation and generalised anxiety disorder was not apparent in men (OR=1.13, 95% CI: 0.72 to 1.77; p=0.598). CONCLUSION The absolute numbers of people living in deprived conditions are large worldwide. This, combined with a growing mental health burden means that the findings obtained in this study remain highly relevant. The World Health Organisation has emphasised the need to reduce social and health inequalities. Our findings provide a strong evidence base to this call, showing that the environment needs to be taken into account when developing mental health policy; gender is clearly an important factor when it comes to assessing the impacts of the environment, and promoting good mental health.This work was supported by the Medical Research Council UK (grant number G9502233) and Cancer Research UK (grant number SP2024- 0201 and SP2024-0204)

Factors influencing quality of life following lower limb amputation for peripheral arterial occlusive disease: a systematic review of the literature

Background: The majority of lower limb amputations are undertaken in people with peripheral arterial occlusive disease,\ud and approximately 50% have diabetes. Quality of life is an important outcome in lower limb amputations; little is known\ud about what influences it, and therefore how to improve it.\ud Objectives: The aim of this systematic review was to identify the factors that influence quality of life after lower limb\ud amputation for peripheral arterial occlusive disease.\ud Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science and Cochrane databases were searched to identify\ud articles that quantitatively measured quality of life in those with a lower limb amputation for peripheral arterial occlusive\ud disease. Articles were quality assessed by two assessors, evidence tables summarised each article and a narrative\ud synthesis was performed.\ud Study design: Systematic review.\ud Results: Twelve articles were included. Study designs and outcome measures used varied. Quality assessment scores\ud ranged from 36% to 92%. The ability to walk successfully with a prosthesis had the greatest positive impact on quality\ud of life. A trans-femoral amputation was negatively associated with quality of life due to increased difficulty in walking\ud with a prosthesis. Other factors such as older age, being male, longer time since amputation, level of social support and\ud presence of diabetes also negatively affected quality of life.\ud Conclusion: Being able to walk with a prosthesis is of primary importance to improve quality of life for people with lower\ud limb amputation due to peripheral arterial occlusive disease. To further understand and improve the quality of life of this\ud population, there is a need for more prospective longitudinal studies, with a standardised outcome measure