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1.
Nature ; 555(7698): 633-637, 2018 03 29.
Article in English | MEDLINE | ID: mdl-29443962

ABSTRACT

Now that it is possible to achieve measurement and control fidelities for individual quantum bits (qubits) above the threshold for fault tolerance, attention is moving towards the difficult task of scaling up the number of physical qubits to the large numbers that are needed for fault-tolerant quantum computing. In this context, quantum-dot-based spin qubits could have substantial advantages over other types of qubit owing to their potential for all-electrical operation and ability to be integrated at high density onto an industrial platform. Initialization, readout and single- and two-qubit gates have been demonstrated in various quantum-dot-based qubit representations. However, as seen with small-scale demonstrations of quantum computers using other types of qubit, combining these elements leads to challenges related to qubit crosstalk, state leakage, calibration and control hardware. Here we overcome these challenges by using carefully designed control techniques to demonstrate a programmable two-qubit quantum processor in a silicon device that can perform the Deutsch-Josza algorithm and the Grover search algorithm-canonical examples of quantum algorithms that outperform their classical analogues. We characterize the entanglement in our processor by using quantum-state tomography of Bell states, measuring state fidelities of 85-89 per cent and concurrences of 73-82 per cent. These results pave the way for larger-scale quantum computers that use spins confined to quantum dots.

2.
Phys Rev Lett ; 128(14): 146802, 2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35476478

ABSTRACT

The energies of valley-orbit states in silicon quantum dots are determined by an as yet poorly understood interplay between interface roughness, orbital confinement, and electron interactions. Here, we report measurements of one- and two-electron valley-orbit state energies as the dot potential is modified by changing gate voltages, and we calculate these same energies using full configuration interaction calculations. The results enable an understanding of the interplay between the physical contributions and enable a new probe of the quantum well interface.

3.
Ann Oncol ; 32(10): 1286-1293, 2021 10.
Article in English | MEDLINE | ID: mdl-34284099

ABSTRACT

BACKGROUND: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. PATIENTS AND METHODS: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. RESULTS: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were -0.8 cm2, -4.5 cm2, -4.1 cm2, and -8.0 cm2 respectively. CONCLUSIONS: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.


Subject(s)
Breast Neoplasms , Pharmaceutical Preparations , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cytochrome P-450 CYP2D6/genetics , Female , Genotype , Humans , Tamoxifen
4.
J Intern Med ; 290(2): 404-415, 2021 08.
Article in English | MEDLINE | ID: mdl-33955087

ABSTRACT

AIM: To investigate whether genotyping could be used as a cost-effective screening step, preceding next-generation sequencing (NGS), in molecular diagnosis of familial hypercholesterolaemia (FH) in Swedish patients. METHODS AND RESULTS: Three hundred patients of Swedish origin with clinical suspicion of heterozygous FH were analysed using a specific array genotyping panel embedding 112 FH-causing mutations in the LDLR, APOB and PCSK9 genes. The mutations had been selected from previous reports on FH patients in Scandinavia and Finland. Mutation-negative cases were further analysed by NGS. In 181 patients with probable or definite FH using the Dutch lipid clinics network (DLCN) criteria (score ≥ 6), a causative mutation was identified in 116 (64%). Of these, 94 (81%) were detected by genotyping. Ten mutations accounted for more than 50% of the positive cases, with APOB c.10580G>A being the most common. Mutations in LDLR predominated, with (c.2311+1_2312-1)(2514)del (FH Helsinki) and c.259T>G having the highest frequency. Two novel LDLR mutations were identified. In patients with DLCN score < 6, mutation detection rate was significantly higher at younger age. CONCLUSION: A limited number of mutations explain a major fraction of FH cases in Sweden. Combination of selective genotyping and NGS facilitates the clinical challenge of cost-effective genetic screening in suspected FH. The frequency of APOB c.10580G>A was higher than previously reported in Sweden. The lack of demonstrable mutations in the LDLR, APOB and PCSK9 genes in ~1/3 of patients with probable FH strongly suggests that additional genetic mechanisms are to be found in phenotypic FH.


Subject(s)
Founder Effect , Genetic Testing , Genotype , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Apolipoprotein B-100/genetics , Female , Humans , Male , Middle Aged , Mutation/genetics , Proprotein Convertase 9/genetics , Receptors, LDL/genetics , Sweden
5.
Phys Rev Lett ; 127(12): 127701, 2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34597063

ABSTRACT

Semiconductor quantum dots containing more than one electron have found wide application in qubits, where they enable readout and enhance polarizability. However, coherent control in such dots has typically been restricted to only the lowest two levels, and such control in the strongly interacting regime has not been realized. Here we report quantum control of eight different transitions in a silicon-based quantum dot. We use qubit readout to perform spectroscopy, revealing a dense set of energy levels with characteristic spacing far smaller than the single-particle energy. By comparing with full configuration interaction calculations, we argue that the dense set of levels arises from Wigner-molecule physics.

6.
Nanotechnology ; 33(12)2021 Dec 28.
Article in English | MEDLINE | ID: mdl-34962232

ABSTRACT

The simulated noise used to benchmark wavelet edge detection in this work was described incorrectly. The correct description is given here, and new results based on noise that matches the original description are provided. The results support our original conclusion, which is that wavelet edge detection outperforms thresholding in the presence of white noise and 1/fnoise.

7.
Eur J Pediatr ; 180(5): 1603-1610, 2021 May.
Article in English | MEDLINE | ID: mdl-33469713

ABSTRACT

The aim of this study was to assess whether home phototherapy was feasible and safe in a cohort of otherwise healthy term-born neonates who fulfilled the criteria for in-hospital phototherapy. This was a randomized controlled trial in which term newborns with a total serum bilirubin of 18-24 mg/dL (300-400 µmol) were randomized to either home phototherapy or conventional in-hospital phototherapy. The primary outcome measurements were safety and efficacy, length of stay and the number of failed treatments. The secondary outcomes were the number of blood samples and weight gain during treatment. One hundred forty-seven patients were recruited, 69 patients randomized to conventional phototherapy and 78 to home phototherapy. The results showed that no patients needed blood exchange and only 4% of the patients allocated to home phototherapy were admitted to the hospital. The duration of phototherapy, length of stay, amount of blood tests and weight change showed no statically significant differences.Conclusion: Home phototherapy could be a safe alternative to inpatient phototherapy for otherwise healthy newborns with hyperbilirubinemia if daily checkups and 24/7 telephone support can be provided. The parents should be informed to contact the hospital immediately if they fail to perform the treatment at home.Trial registration: Clinicaltrials.gov NCT03536078 What is Known: • Phototherapy in the hospital is a safe and effective treatment without major side effects. • Fibre optic equipment has made the choice of home phototherapy possible. What is New: • This is the first randomized controlled trial comparing home phototherapy with hospital phototherapy. • Results indicate that home phototherapy could be considered as a safe and feasible alternative when performed according to instructions given, to hospital treatment for otherwise healthy term newborns.


Subject(s)
Hyperbilirubinemia, Neonatal , Hyperbilirubinemia , Hospitalization , Hospitals , Humans , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Phototherapy , Treatment Outcome
8.
Br J Surg ; 107(4): 413-421, 2020 03.
Article in English | MEDLINE | ID: mdl-32031251

ABSTRACT

BACKGROUND: The growing problem of opioid misuse has become a serious crisis in many countries. The role of trauma as a gateway to opioid use is currently not determined. The study was undertaken to assess whether traumatic injury might be associated with chronic opioid use and accompanying increased long-term mortality. METHODS: Injured patients and controls from Sweden were matched for age, sex and municipality. After linkage to Swedish health registers, opioid consumption was assessed before and after trauma. Among injured patients, logistic regression was used to investigate factors associated with chronic opioid use, assessed by at least one written and dispensed prescription in the second quarter after trauma. Cox regression was employed to study excess risk of mortality. In addition, causes of death for postinjury opioid users were explored. RESULTS: Some 13 309 injured patients and 70 621 controls were analysed. Exposure to trauma was independently associated with chronic opioid use (odds ratio 3·28, 95 per cent c.i. 3·02 to 3·55); this use was associated with age, low level of education, somatic co-morbidity, psychiatric co-morbidity, pretrauma opioid use and severe injury. The adjusted hazard ratio for death from any cause 6-18 months after trauma for chronic opioid users was 1·82 (95 per cent c.i. 1·34 to 2·48). Findings were similar in a subset of injured patients with no pretrauma opioid exposure. CONCLUSION: Traumatic injury was associated with chronic opioid use. These patients have an excess risk of death in the 6-18 months after trauma.


ANTECEDENTES: El uso indebido de opioides es un problema creciente que se ha convertido en una grave crisis en muchos países. No se ha analizado el papel de las lesiones traumáticas como puerta de entrada al uso de opioides. Se estableció la hipótesis de que una lesión traumática podría asociarse con el uso crónico de opioides y acompañarse de un aumento de la mortalidad a largo plazo. MÉTODOS: Se ajustaron por edad, sexo y municipio a los pacientes suecos con lesiones traumáticas y sus controles. Después de vincular varios registros de salud suecos, se evaluó el consumo de opioides antes y después de la lesión traumática. En los pacientes con lesiones traumáticas, se utilizó una regresión logística para definir los factores asociados con el uso crónico de opioides, definida como una receta prescrita y dispensada en el segundo trimestre después de la lesión traumática, y ​​una regresión de Cox para estudiar el exceso de riesgo de mortalidad. Además, se exploraron las causas de muerte de los usuarios de opioides postraumáticos. RESULTADOS: Se analizaron 13.309 pacientes con lesiones traumáticas y 70.621 controles. La exposición a una lesión traumática se asoció de forma independiente con el uso crónico de opioides, (razón de oportunidades, odds ratio, OR) OR 3,3 (i.c. del 95% 3,0-3,6), y dicho uso se asoció con la edad, el bajo nivel educativo, las comorbilidad físicas y psiquiátricas, el uso previo de opioides y la gravedad de las lesiones. El cociente de riesgos instantáneos, hazard ratio, HR ajustado de muerte por cualquier causa a los 6-18 meses de la lesión traumática para los consumidores crónicos de opioides fue de 1,8 (i.c. del 95% 1,3-2,5). En un subconjunto de pacientes con lesiones traumáticas sin exposición previa a los opioides, los hallazgos fueron similares. CONCLUSIÓN: La lesión traumática se asoció con el uso crónico de opioides. Estos pacientes presentan un exceso de riesgo de mortalidad entre los 6 y 8 meses después del trauma.


Subject(s)
Opioid-Related Disorders/etiology , Wounds and Injuries/complications , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cause of Death , Female , Humans , Logistic Models , Male , Middle Aged , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/mortality , Proportional Hazards Models , Registries , Risk Factors , Sweden/epidemiology , Treatment Outcome , Wounds and Injuries/mortality , Young Adult
9.
Nanotechnology ; 31(50): 505001, 2020 Dec 11.
Article in English | MEDLINE | ID: mdl-33043895

ABSTRACT

We present an improved fabrication process for overlapping aluminum gate quantum dot devices on Si/SiGe heterostructures that incorporates low-temperature inter-gate oxidation, thermal annealing of gate oxide, on-chip electrostatic discharge (ESD) protection and an optimized interconnect process for thermal budget considerations. This process reduces gate-to-gate leakage, damage from ESD, dewetting of aluminum and formation of undesired alloys in device interconnects. Additionally, cross-sectional scanning transmission electron microscopy (STEM) images elucidate gate electrode morphology in the active region as device geometry is varied. We show that overlapping aluminum gate layers homogeneously conform to the topology beneath them, independent of gate geometry and identify critical dimensions in the gate geometry where pattern transfer becomes non-ideal, causing device failure.

10.
BMC Geriatr ; 20(1): 436, 2020 10 31.
Article in English | MEDLINE | ID: mdl-33129257

ABSTRACT

BACKGROUND: Providing support to others has been shown to be beneficial to older adults. As people age, their health and social relationships change. These changes may also relate to changes in social support provision. We examined the trajectory of instrumental support provision by older people in three European regions throughout 11 years of follow-up. We then examined the extent to which age at baseline, sex, and region (representing welfare state regime) influenced the variations in the trajectory. METHODS: Data collected from 8354 respondents who had completed at least waves 1 and 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE) was analysed. Instrumental support provision was determined from asking a single question regarding whether the respondent provided help personally for people outside their household. Region, sex, and age at baseline were the main predictors tested. We used growth modelling to address the aims of this study. RESULTS: The northern European region (Sweden and Denmark) had the highest odds ratio of instrumental support provision. The likelihood of being involved in providing instrumental support decreased by 8% annually (OR: 0.916, 95%CI: 0.893,0.940) over the 11 years of follow-up. Older respondents were less likely to provide instrumental support and their trajectories declined faster than those of the younger respondents. Sex difference in instrumental support provision was more apparent among younger-older people in the southern European region. CONCLUSIONS: Older European adults are an important source of instrumental support, especially for their families. The probability of instrumental support provision by European older adults declines over time. Age, sex, and welfare state regime predict this trajectory.


Subject(s)
Data Analysis , Retirement , Aged , Aged, 80 and over , Aging , Europe/epidemiology , Female , Humans , Male , Sweden
11.
Health Promot Int ; 35(2): 187-195, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31219568

ABSTRACT

Aaron Antonovsky advanced the concept of salutogenesis almost four decades ago (Antonovsky, Health, Stress and Coping. Jossey-Bass, San Francisco, CA, 1979; Unravelling the Mystery of Health. Jossey-Bass, San Francisco, CA, 1987). Salutogenesis posits that life experiences shape the sense of coherence (SOC) that helps to mobilize resources to cope with stressors and manage tension successfully (determining one's movement on the health Ease/Dis-ease continuum). Antonovsky considered the three-dimensional SOC (i.e. comprehensibility, manageability, meaningfulness) as the key answer to his question about the origin of health. The field of health promotion has adopted the concept of salutogenesis as reflected in the international Handbook of Salutogenesis (Mittelmark et al., The Handbook of Salutogenesis. Springer, New York, 2016). However, health promotion mostly builds on the more vague, general salutogenic orientation that implies the need to foster resources and capacities to promote health and wellbeing. To strengthen the knowledge base of salutogenesis, the Global Working Group on Salutogenesis (GWG-Sal) of the International Union of Health Promotion and Education produced the Handbook of Salutogenesis. During the creation of the handbook and the regular meetings of the GWG-Sal, the working group identified four key conceptual issues to be advanced: (i) the overall salutogenic model of health; (ii) the SOC concept; (iii) the design of salutogenic interventions and change processes in complex systems; (iv) the application of salutogenesis beyond health sector. For each of these areas, we first highlight Antonovsky's original contribution and then present suggestions for future development. These ideas will help guide GWG-Sal's work to strengthen salutogenesis as a theory base for health promotion.


Subject(s)
Forecasting , Health Promotion , Sense of Coherence , Health Status , Humans
12.
Anal Chem ; 91(9): 5599-5604, 2019 05 07.
Article in English | MEDLINE | ID: mdl-30938146

ABSTRACT

An environmentally recovered, mixed Pu-U hot particle from the Thule accident, Greenland has been analyzed by Scanning Electron Microscopy and a large-geometry Secondary Ion Mass Spectrometry based Scanning Ion Imaging (SII) method for simultaneous 235,236,238U and 239,240Pu isotope compositions. This SII technique permits the visual assessment of the spatial distribution of the isotopes of U and Pu and can be used to obtain quantitative isotope ratios in any user-defined square region up to a few 100 µm in size. The particle measured here has two resolvable U isotopic compositions with a single composition of weapons grade Pu. The bulk of the particle has enriched U and weapons-grade Pu with 235U/238U, 236U/238U, and 240Pu/239Pu of 1.12 ± 0.04, 0.006 ± 0.002, 0.054 ± 0.004, respectively (2σ). The Pu isotopic ratio was consistent across the sample but 239Pu/238Uraw decreased from 1.99 ± 0.07 to 0.11 ± 0.04 (2σ) corresponding to the area of the particle with a resolvably different U isotope composition. This portion of the particle has 235U/238U, 236U/238U, and 240Pu/239Pu ratios of 0.11 ± 0.04, 0.001 ± 0.002, and 0.05 ± 0.04, respectively (2σ). The origin of the less enriched U could be environmental that mixed with the particle or heterogeneously enriched U from the weapons. The heterogeneity of hot particles on a micrometer scale highlights the need for spatially resolved techniques to avoid mixing during a bulk or whole particle analysis, as the mixing end-members here would have been lost, and the measured ratios would have been inaccurate.

13.
BMC Infect Dis ; 19(1): 1052, 2019 Dec 16.
Article in English | MEDLINE | ID: mdl-31842764

ABSTRACT

BACKGROUND: The diagnosis of infective endocarditis (IE) is based on microbiological analyses and diagnostic imaging of cardiac manifestations. Echocardiography (ECHO) is preferred for visualization of IE-induced cardiac manifestations. We investigated associations between bacterial infections and IE manifestations diagnosed by ECHO. METHODS: In this cohort study, data from patients aged 18 years or above, with definite IE admitted at the Karolinska University Hospital between 2008 and 2017 were obtained from Swedish National Registry of Endocarditis. Bacteria registered as pathogen were primarily selected from positive blood culture and for patients with negative blood culture, bacteria found in culture or PCR from postoperative material was registered as pathogen. Patients with negative results from culture or PCR, and patients who did not undergo ECHO during hospital stay, were excluded. IE manifestations diagnosed by ECHO were obtained from the registry. Chi-squared test and two-sided Fisher's exact test was used for comparisons between categorical variables, and student's t test was used for continuous numerical variables. Multivariable analyses were performed using logistic regression. Secular trend analyses were performed using linear regression. Associations and the strength between the variables were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered significant. RESULTS: The most common bacteria were Staphylococcus aureus (n = 239, 49%) and viridans group streptococci (n = 102, 21%). The most common manifestations were vegetation in the mitral (n = 195, 40%), aortic (n = 190, 39%), and tricuspid valves (n = 108, 22%). Associations were seen between aortic valve vegetations and Enterococcus faecalis among patients with native aortic valves, between mitral valve vegetations and streptococci of group B or viridans group, between tricuspid valve vegetations and S. aureus among patients with intravenous drug abuse, and between perivalvular abscesses as well as cardiovascular implantable electronic device (CIED)-associated IE and coagulase negative staphylococci (all P < 0.05). CONCLUSIONS: Associations were found between certain bacterial species and specific ECHO manifestations. Our study contributes to a better understanding of IE manifestations and their underlying bacterial etiology, which pathogens can cause severe infections and might require close follow-up and surgical treatment.


Subject(s)
Endocarditis, Bacterial/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , Streptococcal Infections/microbiology , Viridans Streptococci/isolation & purification , Abscess/microbiology , Adult , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/microbiology , Echocardiography , Endocarditis, Bacterial/blood , Endocarditis, Bacterial/diagnostic imaging , Endocarditis, Bacterial/surgery , Female , Hospital Mortality , Hospitals, University , Humans , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/microbiology , Registries , Retrospective Studies , Staphylococcus aureus/genetics , Substance Abuse, Intravenous/microbiology , Sweden , Treatment Outcome , Viridans Streptococci/genetics
14.
J Intern Med ; 284(6): 674-684, 2018 12.
Article in English | MEDLINE | ID: mdl-29974534

ABSTRACT

BACKGROUND: Familial hypercholesterolemia could be prevalent among patients with acute coronary syndrome. OBJECTIVE: To investigate both the frequency of causative mutations for familial hypercholesterolemia (FH) and the optimal selection of patients for genetic testing among patients with an acute coronary syndrome (ACS). METHODS: One hundred and sixteen patients with an ACS during 2009-2015 were identified through the SWEDEHEART registry. Patients who had either a high total cholesterol level ≥7 mmol L-1 combined with a triglyceride level ≤2.6 mmol L-1 , or were treated with lipid-lowering medication and had a total cholesterol level >4.9 mmol L-1 and a triglyceride level ≤2.6 mmol L-1 were included. Genetic testing was performed first with a regionally designed FH mutation panel (118 mutations), followed by testing with a commercially available FH genetic analysis (Progenika Biopharma). RESULTS: A total of 6.9% (8/116) patients had a FH-causative mutation, all in the LDL-receptor. Five patients were detected on the panel, and further testing of the remaining 111 patients detected an additional 3 FH-causative mutations. Baseline characteristics were similar in FH-positive and FH-negative patients with respect to age, gender, prior ACS and diabetes. Patients with a FH-causative mutation had higher Dutch Lipid Clinical Network (DLCN) score (5.5 (5.0-6.5) vs 3.0 (2.0-5.0), P < 0.001) and a higher low-density lipoprotein level (5.7 (4.7-6.5) vs 4.9 (3.5-5.4), P = 0.030). The Dutch Lipid Clinical Network (DLCN) score had a good discrimination with an area under the curve of 0.856 (95% CI 0.763-0.949). CONCLUSION: Genetic testing for FH should be considered in patients with ACS and high DLCN score.


Subject(s)
Acute Coronary Syndrome/genetics , Cholic Acids/blood , Genetic Testing , Steroid Metabolism, Inborn Errors/genetics , Acute Coronary Syndrome/etiology , Aged , Cholesterol/blood , Cholic Acids/genetics , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Steroid Metabolism, Inborn Errors/complications , Survivors , Triglycerides/blood
15.
J Endocrinol Invest ; 41(6): 691-701, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29168078

ABSTRACT

PURPOSE: Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals. METHODS: Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle + sham operation (GK-V). Body weight, glucose parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified by optical projection tomography. RESULTS: After surgery, body weight development was equal among groups (P g = 0.75). Fasting and stimulated gastrin increased for GK-PPI and GK-SG vs. GK-V (p < 0.05 for all). Fasting blood glucose was decreased for GK-PPI and GK-SG vs. GK-V (p < 0.05 and p = 0.052). HbA1c was lower for GK-SG vs. GK-V at 6 weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks postoperative (p < 0.05 for all); a borderline difference was observed for GK-SG vs. GK-V at 18 weeks (p = 0.054). Total- and LDL cholesterol was elevated for GK-PPI compared to the other two groups (p < 0.05 for all). Beta-cell mass did not differ among groups (p = 0.35). CONCLUSIONS: Hypergastrinemia following sleeve gastrectomy and pantoprazole has a similar, modest effect on glycemic control in Goto-Kakizaki rats but does not enhance beta-cell mass after 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.


Subject(s)
2-Pyridinylmethylsulfinylbenzimidazoles/pharmacology , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Type 2/therapy , Gastrectomy/methods , Gastrins/pharmacology , Insulin-Secreting Cells/pathology , Animals , Combined Modality Therapy , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/pathology , Hormones/pharmacology , Insulin-Secreting Cells/drug effects , Male , Pantoprazole , Rats
17.
J Intern Med ; 281(6): 575-585, 2017 06.
Article in English | MEDLINE | ID: mdl-28145001

ABSTRACT

BACKGROUND: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited. METHODS: Kinetics of autologous 125 I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg-1 day-1 ). In seven patients with gallstones treated with CDCA for 3 weeks before cholecystectomy, liver biopsies were collected and analysed for enzyme activities and for specific LDLR binding. Serum samples obtained before treatment and at surgery were analysed for markers of lipid metabolism, lipoproteins and the LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9). RESULTS: Chenodeoxycholic acid treatment increased plasma LDL cholesterol by ~10% as a result of reduced clearance of plasma LDL-apolipoprotein (apo)B; LDL production was somewhat reduced. The reduction in LDL clearance occurred within 1 day after initiation of treatment. In CDCA-treated patients with gallstones, hepatic microsomal cholesterol 7α-hydroxylase and HMG-CoA reductase activities were reduced by 83% and 54%, respectively, and specific LDLR binding was reduced by 20%. During treatment, serum levels of fibroblast growth factor 19 and total and LDL cholesterol increased, whereas levels of 7α-hydroxy-4-cholesten-3-one, lathosterol, PCSK9, apoA-I, apoC-III, lipoprotein(a), triglycerides and insulin were reduced. CONCLUSIONS: Chenodeoxycholic acid has a broad influence on lipid metabolism, including reducing plasma clearance of LDL. The reduction in circulating PCSK9 may dampen its effect on hepatic LDLRs and plasma LDL cholesterol. Further studies of the effects of other FXR agonists on cholesterol metabolism in humans seem warranted, considering the renewed interest for such therapy in liver disease and diabetes.


Subject(s)
Apolipoprotein C-III/drug effects , Chenodeoxycholic Acid/pharmacology , Cholesterol, LDL/drug effects , Lipoprotein(a)/drug effects , Proprotein Convertase 9/drug effects , Receptors, Cytoplasmic and Nuclear/agonists , Apolipoprotein C-III/blood , Chenodeoxycholic Acid/therapeutic use , Cholesterol, LDL/blood , Gallstones/drug therapy , Humans , Liver/enzymology , Male , Proprotein Convertase 9/blood , Receptors, LDL/metabolism
18.
Acta Neurol Scand ; 135(6): 608-613, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27439693

ABSTRACT

OBJECTIVE: The objective of this nationwide study was to analyze how functional status and socioeconomic status affect return to work (RTW) among younger patients with first-time stroke in a Sweden. MATERIAL AND METHODS: This register-based cohort study included employed patients aged 25-55 with first-time stroke between 2008 and 2011 and primary outcome was RTW within 1 year after stroke. Data regarding functional status and employment status were retrieved from the Swedish Stroke Register, Riksstroke, and socioeconomic data (income, education, and country of birth) from Statistics Sweden. RESULTS: We included 2539 patients who had answered the question on RTW, and 1880 (74.0%) had RTW within 12 months. Patients with low income (69.9% in lowest income group vs 79.9% in highest group, P<.001), patients born in countries outside the Nordic countries (Sweden 75.5%, Nordic countries 74.3%, European countries 61.7%, other countries 57.3%, P<.001), and the youngest patients (25-34, 63.1%; 35-44, 75.9%; 45-55, 74.3%; P=.008) were less likely to RTW. Pain, low mood, and answering the questionnaire with help were more common in low socioeconomic groups, and when adjusting for these variables, together with age and sex, income and country of birth were no longer independent predictors for RTW. CONCLUSION: Patients with low socioeconomic status less often RTW 1 year after stroke.Impaired functional status after stroke is more common in patients with lower socioeconomic status and mediates socioeconomic differences in RTW. Improvement of functional status should be targeted to facilitate RTW among stroke patients with low socioeconomic status.


Subject(s)
Return to Work/statistics & numerical data , Stroke Rehabilitation/statistics & numerical data , Stroke/epidemiology , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Scandinavian and Nordic Countries
19.
Br J Anaesth ; 119(5): 1030-1038, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29077818

ABSTRACT

BACKGROUND: Many patients undergoing anaesthesia and surgery experience postoperative complications. Our aim was to investigate whether a systematic follow-up smartphone-based assessment, using recovery assessment by phone points (RAPP) compared with standard care, had a positive effect on day surgery patients' postoperative recovery. We also investigated whether there were differences in women and men's recovery and recovery scores. METHODS: The study was a single-blind, multicentre randomized controlled trial. A total of 997 patients were randomly allocated to either RAPP or standard care. The Swedish web version of a quality of recovery (SwQoR) questionnaire was used to evaluate the patients' postoperative recovery, either on paper or using an application (RAPP) on postoperative days seven and 14. RESULTS: On postoperative day seven the RAPP group reported significantly better values in seven out of 24 items of the SwQoR: sleeping difficulties; not having a general feeling of wellbeing; having difficulty feeling relaxed/comfortable; and dizziness; headache; pain in the surgical wound; and a swollen surgical wound compared with the control group, implying a good postoperative recovery. Both men and women in the RAPP group reported significantly better values (and, hence good postoperative recovery) compared with the control group in the items sleeping difficulties; not having a general feeling of wellbeing and pain in the surgical wound. CONCLUSIONS: Measurement of patient-reported outcomes using a smartphone-based application was associated with decreased discomfort from several postoperative symptoms. Systematic e-assessment can thereby increase patients' quality of recovery and identify key areas for improvement in perioperative care. CLINICAL TRIAL REGISTRATION: NCT02492191.


Subject(s)
Ambulatory Surgical Procedures/rehabilitation , Mobile Applications , Postoperative Care/methods , Smartphone , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Sex Factors , Single-Blind Method , Sweden , Young Adult
20.
Acta Paediatr ; 106(2): 268-273, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27797408

ABSTRACT

AIM: This study established the incidence of acute rhinosinusitis and related orbital complications in tertiary care in Stockholm County and surveyed the clinical outcomes. METHODS: This was a population-based, retrospective, observational study, from July 1, 2003 to June 30, 2007, of the hospital admissions records of 213 children up to five years old, with a diagnosis of sinusitis and related complications. RESULTS: Preseptal cellulitis was present in 171 of the 213 admissions, which equated to an incidence of orbital complications due to acute rhinosinusitis of 36 per 100 000 people per year (95% confidence interval 26-49). Postseptal complications occurred in seven cases. The incidence rate ratio for hospitalisation of children less than two years old with rhinosinusitis compared with children aged 2-5 years was 2.8 (95% confidence interval 1.8-4.4). The incidence among boys was 53 per 100 000 people per year and 36 per 100 000 people per year for girls, and the incidence rate ratio was 1.5 (95% confidence interval 1.0-2.3). The most common bacterial finding was Streptococcus pneumoniae. CONCLUSION: Most children hospitalised for acute rhinosinusitis had an orbital complication, and this was more common in children under the age of two years and boys. Severe postseptal complications were rare.


Subject(s)
Orbital Diseases/etiology , Rhinitis/complications , Sinusitis/complications , Anti-Bacterial Agents/administration & dosage , Child, Preschool , Female , Hospitalization , Humans , Infant , Male , Orbital Diseases/drug therapy , Orbital Diseases/epidemiology , Orbital Diseases/microbiology , Retrospective Studies , Rhinitis/diagnostic imaging , Rhinitis/drug therapy , Rhinitis/microbiology , Sinusitis/diagnostic imaging , Sinusitis/drug therapy , Sinusitis/microbiology , Sweden/epidemiology , Tomography, X-Ray Computed
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