The Last Swiddens of Sarawak, Malaysia

Swidden cultivation was observed to be under pressure but still persisting in many areas in Sarawak, Malaysia around 2000–2003. Since then rapid development of smallholder oil palm and rubber, continuing urbanization and rural to urban migration appear to have considerably reduced the area under swidden cultivation. With the aim of understanding the extent and impacts of this development, 55 households in three communities that were interviewed in 2002–2003 were re-interviewed in 2011. In an area with rapid oil palm development, the households engaged in smallholder oil palm production have experienced considerable improvements in income and wealth whereas the other households have experienced more limited wealth increases or even a decline in income. Many households have decreased or abandoned cultivation of upland rice, which used to be the core of the swidden cultivation system, and the upland soils in the area are now dominated by oil palm. In another area, where no oil palm development has taken place because of a hydroelectric dam, upland rice fields under swidden cultivation have also decreased and new high yielding rubber is now being planted because of the favorable rubber prices. Moreover, tourism has in this area gained further economic importance and overtaken agriculture as the main economic activity of households. The demise of swidden has not yet occurred in Sarawak, but a continued decline has been observed. However, there is a possibility that the new smallholder oil palm and rubber may provide an opportunity for a new type of ‘productive fallow’ that will allow continued cultivation of upland rice on a small scale

Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients

Objective: To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis.Methods: 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13.7 months (range from 2.7 to 73.8 months). Safety, tolerability, survival and change in ALSFRS-R were observed. Hematopoietic stem cells were monitored by flow cytometry analysis of circulating CD34+ and CD34+CD38− cells, and peripheral cytokines were assessed by electrochemoluminescence throughout the intervention period. Analysis of immunological and hematological markers was conducted.Results: Long term and individually adapted treatment with G-CSF was well tolerated and safe. G-CSF led to a significant mobilization of hematopoietic stem cells into the peripheral blood. Higher mobilization capacity was associated with prolonged survival. Initial levels of serum cytokines, such as MDC, TNF-beta, IL-7, IL-16, and Tie-2 were significantly associated with survival. Continued application of G-CSF led to persistent alterations in serum cytokines and ongoing measurements revealed the multifaceted effects of G-CSF.Conclusions: G-CSF treatment is feasible and safe for ALS patients. It may exert its beneficial effects through neuroprotective and -regenerative activities, mobilization of hematopoietic stem cells and regulation of pro- and anti-inflammatory cytokines as well as angiogenic factors. These cytokines may serve as prognostic markers when measured at the time of diagnosis. Hematopoietic stem cell numbers and cytokine levels are altered by ongoing G-CSF application and may potentially serve as treatment biomarkers for early monitoring of G-CSF treatment efficacy in ALS in future clinical trials

Antibiotic-loaded bone cement in prevention of periprosthetic joint infections in primary total knee arthroplasty: A register-based multicentre randomised controlled non-inferiority trial (ALBA trial)

Introduction The current evidence on the efficacy of antibiotic-loaded bone cement (ALBC) in reducing the risk of periprosthetic joint infections (PJI) after primary joint reconstruction is insufficient. In several European countries, the use of ALBC is routine practice unlike in the USA where ALBC use is not approved in low-risk patients. Therefore, we designed a double-blinded pragmatic multicentre register-based randomised controlled non-inferiority trial to investigate the effects of ALBC compared with plain bone cement in primary total knee arthroplasty (TKA). Methods and analysis A minimum of 9,172 patients undergoing full-cemented primary TKA will be recruited and equally randomised into the ALBC group and the plain bone cement group. This trial will be conducted in Norwegian hospitals that routinely perform cemented primary TKA. The primary outcome will be risk of revision surgery due to PJI at 1-year of follow-up. Secondary outcomes will be: risk of revision due to any reason including aseptic loosening at 1, 6, 10 and 20 years of follow-up; patient-related outcome measures like function, pain, satisfaction and health-related quality of life at 1, 6 and 10 years of follow-up; risk of changes in the microbial pattern and resistance profiles of organisms cultured in subsequent revisions at 1, 6, 10 and 20 years of follow-up; cost-effectiveness of routine ALBC versus plain bone cement use in primary TKA. We will use 1:1 randomisation with random permuted blocks and stratify by participating hospitals to randomise patients to receive ALBC or plain bone cement. Inclusion, randomisation and follow-up will be through the Norwegian Arthroplasty Register. Ethics and dissemination The trial was approved by the Western Norway Regional Committees on Medical and Health Research Ethics (reference number: 2019/751/REK vest) on 21 June 2019. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT04135170.publishedVersio

Multicenter European Prevalence Study of Neurocognitive Impairment and Associated Factors in HIV Positive Patients

We conducted a cross-sectional study in 448 HIV positive patients attending five European outpatient clinics to determine prevalence of and factors associated with neurocognitive impairment (NCI) using computerized and pen-and-paper neuropsychological tests. NCI was defined as a normalized Z score ≤-1 in at least 2 out of 5 cognitive domains. Participants' mean age was 45.8 years; 84% male; 87% white; 56% university educated; median CD4 count 550 cells/mm(3); 89% on antiretroviral therapy. 156 (35%) participants had NCI, among whom 26 (17%; 5.8% overall) reported a decline in activities of daily living. Prevalence of NCI was lower in those always able to afford basic needs (adjusted prevalence ratio [aPR] 0.71, 95% confidence interval [CI] 0.54-0.94) or with a university education (aPR 0.72, 95% CI 0.54-0.97) and higher in those with severe depressive symptoms (aPR 1.53, 95% CI 1.09-2.14) or a significant comorbid condition (aPR 1.40, 95% CI 1.03-1.90)

Modeling and Bioinformatics Identify Responders to G-CSF in Patients With Amyotrophic Lateral Sclerosis

Objective: Developing an integrative approach to early treatment response classification using survival modeling and bioinformatics with various biomarkers for early assessment of filgrastim (granulocyte colony stimulating factor) treatment effects in amyotrophic lateral sclerosis (ALS) patients. Filgrastim, a hematopoietic growth factor with excellent safety, routinely applied in oncology and stem cell mobilization, had shown preliminary efficacy in ALS. Methods: We conducted individualized long-term filgrastim treatment in 36 ALS patients. The PRO-ACT database, with outcome data from 23 international clinical ALS trials, served as historical control and mathematical reference for survival modeling. Imaging data as well as cytokine and cellular data from stem cell analysis were processed as biomarkers in a non-linear principal component analysis (NLPCA) to identify individual response. Results: Cox proportional hazard and matched-pair analyses revealed a significant survival benefit for filgrastim-treated patients over PRO-ACT comparators. We generated a model for survival estimation based on patients in the PRO-ACT database and then applied the model to filgrastim-treated patients. Model-identified filgrastim responders displayed less functional decline and impressively longer survival than non-responders. Multimodal biomarkers were then analyzed by PCA in the context of model-defined treatment response, allowing identification of subsequent treatment response as early as within 3 months of therapy. Strong treatment response with a median survival of 3.8 years after start of therapy was associated with younger age, increased hematopoietic stem cell mobilization, less aggressive inflammatory cytokine plasma profiles, and preserved pattern of fractional anisotropy as determined by magnetic resonance diffusion tensor imaging (DTI-MRI). Conclusion: Long-term filgrastim is safe, is well-tolerated, and has significant positive effects on disease progression and survival in a small cohort of ALS patients. Developing and applying a model-based biomarker response classification allows use of multimodal biomarker patterns in full potential. This can identify strong individual treatment responders (here: filgrastim) at a very early stage of therapy and may pave the way to an effective individualized treatment option

Moments of Escape

Fantasy—a world to live in, believe in, or to loose yourself in. The great realm of fantasy and horror attract us with their beauty and grace, fascinate us with their magic, lure us with the promises of fabulous wealth, and unimaginable power, which is free for the taking, with no twinge of conscience. Moments of Escape will do more than entertain and delight readers. It will offer mystical journeys through enchanted landscapes and capture readers in the horror of the night. Readers who desire harrowing excursion into the darkest corners of the imagination or simple blood-lust will be delighted. To these readers this thesis is dedicated, this journey into fantasy and horror