| 1. |
- Enroth, Stefan, et al.
(författare)
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A strand specific high resolution normalization method for chip-sequencing data employing multiple experimental control measurements
- 2012
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Ingår i: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 7, s. 2-
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-throughput sequencing is becoming the standard tool for investigating protein-DNA interactions or epigenetic modifications. However, the data generated will always contain noise due to e. g. repetitive regions or non-specific antibody interactions. The noise will appear in the form of a background distribution of reads that must be taken into account in the downstream analysis, for example when detecting enriched regions (peak-calling). Several reported peak-callers can take experimental measurements of background tag distribution into account when analysing a data set. Unfortunately, the background is only used to adjust peak calling and not as a preprocessing step that aims at discerning the signal from the background noise. A normalization procedure that extracts the signal of interest would be of universal use when investigating genomic patterns.Results: We formulated such a normalization method based on linear regression and made a proof-of-concept implementation in R and C++. It was tested on simulated as well as on publicly available ChIP-seq data on binding sites for two transcription factors, MAX and FOXA1 and two control samples, Input and IgG. We applied three different peak-callers to (i) raw (un-normalized) data using statistical background models and (ii) raw data with control samples as background and (iii) normalized data without additional control samples as background. The fraction of called regions containing the expected transcription factor binding motif was largest for the normalized data and evaluation with qPCR data for FOXA1 suggested higher sensitivity and specificity using normalized data over raw data with experimental background.Conclusions: The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously. Our evaluation on both synthetic and experimental data suggests that the method is successful in removing background noise.
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| 2. |
- Andersson, Björn, 1952, et al.
(författare)
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Trestad2 : Storstädernas satsning mot cannabis : delrapport för tiden jan 2012 - sep 2013.
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport är en halvtidsdokumentation av den storstadssatsning som mellan 2012 och 2014 genomförs i Stockholm, Göteborg och Malmö med syfte att minska användande av cannabis hos unga. Författarna till rapporten är medlemmar av den övergripande forskargrupp som utsetts av de tre medverkande storstäderna för att följa, dokumentera och utvärdera projektet som helhet. Den övergripande forskargruppen kommer att presentera sin slutrapport sommaren/hösten 2014. Halvtidsdokumentationen avser perioden från januari 2012 till september 2013 och har tillkommit på initiativ av den övergripande forskargruppen för att dokumentera storstadssatsningens förlopp samt för att skapa ett underlag som kan användas såväl under den återstående projekttiden, som vid slutrapportering av hela storstadssatsningen. Rapporten presenterades på ett seminarium med de tre medverkande städerna i Malmö den 3 februari 2014.
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| 3. |
- Andersson, Cecilia K, et al.
(författare)
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Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis
- 2011
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 12:139
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods: Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-beta. Results: In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-beta. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-beta, correlated negatively with patient lung function. Conclusions: The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.
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| 4. |
- Andersson, Niklas, 1970, et al.
(författare)
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Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 175:3, s. 695-703
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Tidskriftsartikel (refereegranskat)abstract
- Both ovariectomy (Ovx) and gastrectomy (Gx) induce osteopaenia in rats and humans. While the effect of Ovx has been ascribed to oestrogen deficiency, the underlying mechanism behind Gx is poorly understood. Alendronate, oestrogen and parathyroid hormone (PTH) are known to prevent the osteopaenia induced by Ovx in rats. The purpose of the present study was to determine whether alendronate, oestrogen or PTH could also prevent Gx-evoked osteopaenia. Rats were Ovx-, Gx-, or were sham-operated (Sham) and were then treated with alendronate (50 micro g/kg/day), oestrogen (10 micro g/kg/day) or PTH(1-84) (75 micro g/kg/day) for eight weeks. At sacrifice, serum PTH was unaffected by surgery (Ovx, 64+/-8 pg/ml; Gx, 75+/-13 pg/ml; Sham, 58+/-11 pg/ml). The bone mineral density (BMD) of the fifth lumbar vertebra (L5) was analysed. Ovx and Gx reduced the BMD (ash weight/Volume) of the L5 by 15+/-4% and 22+/-3% respectively. Trabecular BMD and the cortical bone mineral content (BMC) of the femur were assessed using peripheral computed tomography. Both Ovx and Gx markedly reduced trabecular BMD in the metaphyseal area of the distal femur (Ovx, -37+/-7%; Gx, -49+/-7%). The cortical BMC of the femur was only slightly reduced. Alendronate prevented trabecular bone loss after both Ovx and Gx, while oestrogen and PTH prevented trabecular bone loss after Ovx but not after Gx. In conclusion, the bisphosphonate alendronate prevented both Ovx- and Gx-induced trabecular bone loss. In contrast, PTH and oestrogen prevented Ovx-induced but not Gx-induced trabecular bone loss, suggesting that the mechanism behind the trabecular bone loss in Ovx rats differs from that in Gx rats. The results support the notion that the mechanism of action for the bone-sparing effect of these drugs differs. The ability of alendronate, and probably also other bisphosphonates, to prevent Gx-evoked osteopaenia in the rat might be of potential clinical interest when dealing with post-Gx osteopaenia in humans.
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| 5. |
- Andersson, Niklas, 1970, et al.
(författare)
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Pharmacological treatment of osteopenia induced by gastrectomy or ovariectomy in young female rats.
- 2004
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Ingår i: Acta orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470 .- 1651-1964. ; 75:2, s. 201-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both gastrectomy (GX) and ovariectomy (OVX) induce osteopenia in man and experimental animals. The present study addresses the question--can alendronate, estrogen or parathyroid hormone (PTH) be used to treat established GX- or OVX -evoked osteopenia? METHODS: Rats were GX-, OVX- or SHAM-operated 8 weeks before starting the treatment with drugs. Each group was then treated for 8 weeks with 50 microg/kg/day alendronate, 10 microg/kg/day estrogen or 75 microg/kg/day PTH(1-84); n = 8 rats/group. Peripheral Quantitative Computed Tomography (pQCT) was used to measure trabecular bone mineral density (BMD) and various cortical bone parameters. RESULTS: At killing, 16 weeks after surgery, GX and OVX rats had a greatly reduced trabecular BMD in the metaphysis of the distal femur (GX -44% and OVX -55%). Alendronate increased the trabecular BMD by 44% in GX rats and by 64% in OVX rats, while PTH increased it by 51% and 115%, respectively. However, estrogen increased the trabecular BMD in GX rats (35%), but not in OVX rats (15%, not significant). Cortical bone parameters were adversely (but moderately) affected by GX, but not by OVX or by treatment with the three drugs. INTERPRETATION: Alendronate, estrogen and PTH restored the trabecular bone loss in rats with an established GX-evoked osteopenia. In contrast, alendronate and PTH, but not estrogen, restored the trabecular bone loss after OVX. Hence, the mechanism underlying GX-evoked bone loss differs from that underlying OVX-evoked bone loss. The ability of alendronate, estrogen and PTH to reverse the GX-evoked osteopenia in the rat may be of clinical interest when dealing with bone loss in humans after GX.
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| 6. |
- Andersson, Niklas, 1970, et al.
(författare)
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Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice.
- 2001
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Ingår i: The Journal of endocrinology. - 0022-0795 .- 1479-6805. ; 170:3, s. 529-37
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Tidskriftsartikel (refereegranskat)abstract
- The recent development of different genetically modified mice with potentially interesting bone phenotypes has increased the demand for effective non-invasive methods to evaluate effects on bone of mice during growth and development, and for drug evaluation. In the present study, the skeleton was analyzed by repeated in vivo scans using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Ovariectomized (ovx) mice treated with parathyroid hormone (PTH) were used as an animal model to evaluate these two techniques at different times after the onset of treatment. Female mice (6 weeks of age) were allocated randomly to four groups: (1) sham-operated+vehicle; (2) ovx+vehicle; (3) sham-operated+PTH(1-84) 150 microg/kg per day; (4) ovx+PTH. Six weeks after ovariectomy the drug treatment began and was continued for 8 weeks. The total body bone mineral content (BMC) and total body areal bone mineral density (BMD) were measured by DXA. Ovariectomy reduced total body BMC and total body areal BMD by 6.2+/-1.7% and 2.6+/-0.9% respectively. No effect of PTH on total body BMC was seen during the treatment period. The trabecular volumetric BMD was measured by pQCT. Ovariectomy reduced the trabecular volumetric BMD by 52+/-6.7%. The pQCT technique detected a clear effect on trabecular volumetric BMD after 2 weeks of PTH treatment (ovx 94+/-29% and sham-operated 46+/-10% more than vehicle-treated). The cortical bone was measured in a mid-diaphyseal pQCT scan of the tibia. Ovariectomy reduced the cortical BMC by 9+/-2%. PTH treatment for 8 weeks increased cortical BMC in ovx mice. In conclusion, the pQCT technique is more sensitive than the DXA technique in the detection of bone loss after ovariectomy and increased bone mass after PTH treatment in mice. Notably, the pQCT, but not the DXA, technique detected a dramatic effect as early as after 2 weeks of PTH treatment. Dynamic pQCT measurements will be useful for monitoring skeletal changes during growth and development, and for drug evaluation in mice.
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| 7. |
- Berman, Anne H, et al.
(författare)
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Teaching digital mental health treatment in theory and practice : a proof-of-concept pilot and feasibility study
- 2023
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Ingår i: International Journal of Behavioral Medicine. ; , s. 66-66, s. 6-7
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Konferensbidrag (refereegranskat)abstract
- Objective: The labor market for mental health professionals increasingly requires competency in digital mental health treatment (DMHT). This presentation targets DMHT practitioners as course developers and teachers, describing proof-of-concept findings based on a) development of a remotely delivered DMHT course; and b) results from a qualitative evaluation of students’ experiences from the first course round.Methods: The course syllabus was developed through two structured workshops, attended by 11 stakeholders with DMHT experience. For the qualitative evaluation, interviews with seven women participants in the first course round were analyzed according to an inductive, phenomenographic approach.Results: The course development process established a 12-week syllabus covering historical development and evidence for DMHT and an 8-week DMHT clinical practicum treating students with common mental health problems. Examination was formulated as individual case reports encompassing reflections on a) the therapist and client roles; b) ethical aspects of DMHT; and c) future innovations for DMHT. The course is offered via a standard learning management system, with the practicum completed on a separate DMHT platform. The qualitative analysis of the first pilot course round, where students role-played therapists and clients, yielded six themes: overall course experience, treatment program and platform, therapist role, client role, supervision and the alliance.Conclusions: This proof-of-concept procedure led to course establishment in two formats: as an ordinary elective course for advanced clinical psychology students, and as a stand-alone national course for health professionals with basic psychotherapy training. Following local adaptation, the course could be replicated at additional universities globally.
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| 8. |
- Berman, Anne H., et al.
(författare)
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Teaching digital mental health treatment in theory and practice : A proof-of-concept pilot and feasibility study
- 2023
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Ingår i: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 30, s. S67-S67
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Improving relationship dynamics positively impacts both partners’ health among couples. However, few studies have investigated sexual and gender minority (SGM) couples’ relationship goals and their experiences toward achieving them.Purpose: The present study investigated SGM couples’ experiences that centered on them working toward or maintaining their relationship goals over time.Method: From a cohort study with SGM couples, a purposive sample of 40 couples was selected and interviewed over Zoom. Interviews were individual-level, semi-structured, and recorded. Thematic analysis was used to analyze the transcripts.Results: Approximately half of the 40 couples identified as gay male couples, a third as lesbian couples, and about one-fifth as queer or gender minority couples. Top three reported relationship goals were 1) improving communication, 2) working on finances, and 3) enhancing intimacy. Feeling emotionally connected, career-related decisions, and improving sexual satisfaction were other commonly reported goals. Overall, most partners felt they made progress toward at least 1 of their 3 relationship goals within the prior 6 months. However, perceived relationship goal progress varied extensively between partners across couple groups. Facilitator-related themes about relationship goal progress included dyadic efforts, having a support system including professional help, and planning. Barrier-related themes included nonexistent or minimal effort, different communication styles, employment and economical struggles, and competing life and health priorities.Conclusion(s): Dyadic efforts and support systems were key toward someone working toward or maintaining their relationships goals. Findings suggest key relationship functioning areas to target in a future multiple health behavior change intervention for SGM couples.
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| 9. |
- Berman, Anne H., Professor, et al.
(författare)
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Transdiagnostic and tailored internet intervention to improve mental health among university students : Research protocol for a randomized controlled trial
- 2024
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Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components.Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned.Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.
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| 10. |
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