Looming struggles over technology for border control

New technologies under development, capable of inflicting pain on masses of people, could be used for border control against asylum seekers. Implementation might be rationalized by the threat of mass migration due to climate change, nuclear disaster or exaggerated fears of refugees created by governments. We focus on taser anti-personnel mines, suggesting both technological countermeasures and ways of making the use of such technology politically counterproductive. We also outline several other types of ‘non-lethal’ technology that could be used for border control and raise human rights concerns: high-powered microwaves, armed robots, wireless tasers, acoustic devices/vortex rings, ionizing and pulsed energy lasers, chemical calmatives, convulsants, bioregulators and malodurants. Whether all these possible border technologies will be implemented is a matter for speculation, but their serious human rights implications warrant advance scrutiny

Adapting the SLIM diabetes prevention intervention to a Dutch real-life setting: joint decision making by science and practice

Background - Although many evidence-based diabetes prevention interventions exist, they are not easily applicable in real-life settings. Moreover, there is a lack of examples which describe the adaptation process of these interventions to practice. In this paper we present an example of such an adaptation. We adapted the SLIM (Study on Lifestyle intervention and Impaired glucose tolerance Maastricht) diabetes prevention intervention to a Dutch real-life setting, in a joint decision making process of intervention developers and local health care professionals. Methods - We used 3 adaptation steps in accordance with current adaptation frameworks. In the first step, the elements of the SLIM intervention were identified. In the second step, these elements were judged for their applicability in a real-life setting. In the third step, adaptations were proposed and discussed for those elements which were deemed not applicable. Participants invited for this process included intervention developers and local health care professionals (n=19). Results - In the first adaptation step, a total of 22 intervention elements were identified. In the second step, 12 of these 22 intervention elements were judged as inapplicable. In the third step, a consensus was achieved for the adaptations of all 12 elements. The adapted elements were in the following categories: target population, techniques, intensity, delivery mode, materials, organisational structure, and political and financial conditions. The adaptations either lay in changing the SLIM protocol (6 elements) or the real-life working procedures (1 element), or a combination of both (4 elements). Conclusions -he positive result of this study is that a consensus was achieved within a relatively short time period (nine months) between the developers of the SLIM intervention and local health care professionals on the adaptations needed to make SLIM applicable in a Dutch real-life setting. Our example shows that it is possible to combine the perspectives of scientists and practitioners, and to find a balance between evidence-base and applicability concerns

Universal flow diagram for the magnetoconductance in disordered GaAs layers

The temperature driven flow lines of the diagonal and Hall magnetoconductance data (G_{xx},G_{xy}) are studied in heavily Si-doped, disordered GaAs layers with different thicknesses. The flow lines are quantitatively well described by a recent universal scaling theory developed for the case of duality symmetry. The separatrix G_{xy}=1 (in units e^2/h) separates an insulating state from a spin-degenerate quantum Hall effect (QHE) state. The merging into the insulator or the QHE state at low temperatures happens along a semicircle separatrix G_{xx}^2+(G_{xy}-1)^2=1 which is divided by an unstable fixed point at (G_{xx},G_{xy})=(1,1).Comment: 10 pages, 5 figures, submitted to Phys. Rev. Let

Cartilage collagen structure upon knee joint distraction and high tibial osteotomy as measured with T2-mapping MRI - post-hoc analyses of two RCTs

Objective High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments for knee osteoarthritis (OA) that have shown good clinical results and cartilage thickness increase. In this exploratory study, cartilage T2 relaxation times, as a measure of collagen structure, are evaluated after both treatments, and compared to natural OA progression. Design Ten patients indicated for total knee arthroplasty (TKA) were treated with KJD (KJDTKA). Thirty patients indicated for HTO were treated with KJD (KJDHTO; n = 10) or HTO (n = 20). 3T T2-mapping MRI scans were performed before and one (KJD groups only) and two years after treatment, from which cartilage was segmented and the volume and T2 relaxation times were calculated. Patients were matched with untreated patients from the Osteoarthritis Initiative (OAI) to compare the change in T2 values over time. Results KJDHTO (n = 8) and HTO (n = 17) patients both showed statistically significant increases in T2 values (worsening) but no volume changes. KJDTKA patients (n = 8) only showed a tendency for (first-year) T2 value increase, and a significant volume increase in the most affected compartment (MAC). There were no significant differences between the three groups. All treated patients combined showed a significantly higher increase in T2 times than untreated patients from the OAI for both femur and tibia. Conclusions KJD and HTO cause an increase in cartilage T2 relaxation times, which could indicate loss or reorganization of collagen structure integrity. In TKA-indicated KJD patients, this goes paired with volume increase, indicating it may be the result of maturation of newly formed cartilage

Identification of QTLs Associated with Callogenesis and Embryogenesis in Oil Palm Using Genetic Linkage Maps Improved with SSR Markers.

Clonal reproduction of oil palm by means of tissue culture is a very inefficient process. Tissue culturability is known to be genotype dependent with some genotypes being more amenable to tissue culture than others. In this study, genetic linkage maps enriched with simple sequence repeat (SSR) markers were developed for dura (ENL48) and pisifera (ML161), the two fruit forms of oil palm, Elaeis guineensis. The SSR markers were mapped onto earlier reported parental maps based on amplified fragment length polymorphism (AFLP) and restriction fragment length polymorphism (RFLP) markers. The new linkage map of ENL48 contains 148 markers (33 AFLPs, 38 RFLPs and 77 SSRs) in 23 linkage groups (LGs), covering a total map length of 798.0 cM. The ML161 map contains 240 markers (50 AFLPs, 71 RFLPs and 119 SSRs) in 24 LGs covering a total of 1,328.1 cM. Using the improved maps, two quantitative trait loci (QTLs) associated with tissue culturability were identified each for callusing rate and embryogenesis rate. A QTL for callogenesis was identified in LGD4b of ENL48 and explained 17.5% of the phenotypic variation. For embryogenesis rate, a QTL was detected on LGP16b in ML161 and explained 20.1% of the variation. This study is the first attempt to identify QTL associated with tissue culture amenity in oil palm which is an important step towards understanding the molecular processes underlying clonal regeneration of oil palm

Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis?: Data from the IMI-APPROACH cohort

Objective To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). Methods IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components. Results Two hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identifed two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically signifcantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2=0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed signifcantly worse lower leg gait (R2=0.18). Higher BMI was signifcantly associated with reduced upper leg function for non-ROA patients (R2=0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed signifcantly worse upper leg gait (R2=0.12). Conclusion Structural OA pathology was signifcantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a signifcant association between OA symptoms (gait) and joint structure.Pathophysiology and treatment of rheumatic disease

Verslag van de 159e zomerbijeenkomst te Den Hoorn

Tijdens de 159e zomervergadering van de NEV, die plaatsvond op Texel van 4 tot 6 juni 2004, zijn 1117 taxa van veertien insectenordes waargenomen. Hoewel ook dit keer wat aantal soorten betreft, kevers de boventoon voerden zijn er geen nieuwe keversoorten voor de provincie Noord-Holland gevonden. Met soortenlijst en lijst van vindplaatse

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients

Background and Aims Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Methods Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Results Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). Conclusions This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes

Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast cancer and endocrine therapy resistance in advanced disease

Background: Patients with Estrogen Receptor α-positive (ER+) Inflammatory Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+ non-IBC (nIBC) patients. The study of ER+ IBC samples might reveal biomarkers for endocrine resistant breast cancer. Materials & methods: Gene expression profiles of ER+ samples from 201 patients were explored for genes that discriminated between IBC and nIBC. Classifier genes were applied onto clinically annotated expression data from 947 patients with ER+ breast cancer and validated with RT-qPCR for 231 patients treated with first-line tamoxifen. Relationships with metastasis-free survival (MFS) and progression-free survival (PFS) following adjuvant and first-line endocrine treatment, respectively, were investigated using Cox regression analysis. Results: A metagene of six genes including the genes encoding for 4-aminobutyrate aminotransferase (ABAT) and Stanniocalcin-2 (STC2) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and remained discriminatory in an independent series of 136 patients. The metagene and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node-negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250 patients treated with adjuvant tamoxifen. Three independent series of in total 411 patients with advanced disease showed increased metagene scores and decreased expression of ABAT and STC2 to be correlated with poor first-line endocrine therapy outcome. The biomarkers remained predictive for first-line tamoxifen treatment outcome in multivariate analysis including traditional factors or published signatures. In an exploratory analysis, ABAT and STC2 protein expression levels had no relation with PFS after first-line tamoxifen. Conclusions: This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance

Protein Kinase A-induced tamoxifen resistance is mediated by anchoring protein AKAP13

Background: Estrogen Receptor alpha (ERaα)-positive breast cancer patients receive endocrine therapy, often in the form of tamoxifen. However, resistance to tamoxifen is frequently observed. A signalling cascade that leads to tamoxifen resistance is dictated by activation of the Protein Kinase A (PKA) pathway, which leads to phosphorylation of ERaα on Serine 305 and receptor activation, following tamoxifen binding. Thus far, it remains elusive what protein complexes enable the PKA-ERaα interaction resulting in ERaα Serine 305 phosphorylation. Methods: We performed immunohistochemistry to detect ERaαSerine 305 phosphorylation in a cohort of breast cancer patients who received tamoxifen treatment in the metastatic setting. From the same tumor specimens, Agilent 44 nK gene expression analyses were performed and integrated with clinicopathological data and survival information. In vitro analyses were performed using MCF7 breast cancer cells, which included immunoprecipitations and Fluorescence Resonance Energy Transfer (FRET) analyses to illustrate ERaα complex formation. siRNA mediated knockdown experiments were performed to assess effects on ERaαSerine 305 phosphorylation status, ERaα/PKA interactions and downstream responsive gene activity. Results: Stratifying breast tumors on ERaα Serine 305 phosphorylation status resulted in the identification of a gene network centered upon AKAP13. AKAP13 mRNA expression levels correlate with poor outcome in patients who received tamoxifen treatment in the metastatic setting. In addition, AKAP13 mRNA levels correlate with ERaαSerine 305 phosphorylation in breast tumor samples, suggesting a functional connection between these two events. In a luminal breast cancer cell line, AKAP13 was found to interact with ERaα as well as with a regulatory subunit of PKA. Knocking down of AKAP13 prevented PKA-mediated Serine 305 phosphorylation of ERaα and abrogated PKA-driven tamoxifen resistance, illustrating that AKAP13 is an essential protein in this process. Conclusions: We show that the PKA-anchoring protein AKAP13 is essential for the phosphorylation of ERaαS305, which leads to tamoxifen resistance both in cell lines and tamoxifen-treated breast cancer patients