GLOBALLY DISTRIBUTED SOFTWARE DEVELOPMENT IN SMALL AND MEDIUM-SIZED ENTERPRISES IN GERMANY: REASONS, LOCATIONS, AND OBSTACLES

Many large enterprises develop their software nowadays in globally distributed settings. By using the option to outsource, the respective enterprises can realize decisive competitive advantages. In order to remain competitive, small and medium-sized enterprises (SMEs) are also forced to follow this trend and to outsource parts of their software development. However, most of the existing studies analyze the outsourcing situation in large enterprises, whereas the position of SMEs is being neglected and remains unclear. Main drivers for software development outsourcing decisions, suitable vendor locations, and problems occurring while realizing such projects may differ between large enterprises and SMEs. Therefore, in this explorative research paper we examine the outsourcing activities of eight SMEs in the German state of Baden-Württemberg. Besides the question why SMEs are choosing the outsourcing option we seek to find out, which countries are best suited for outsourcing activities of SMEs as well as which obstacles in particular hinder these enterprises in successfully conducting software development outsourcing

Scaling of the localization length in linear electronic and vibrational systems with long-range correlated disorder

The localization lengths of long-range correlated disordered chains are studied for electronic wavefunctions in the Anderson model and for vibrational states. A scaling theory close to the band edge is developed in the Anderson model and supported by numerical simulations. This scaling theory is mapped onto the vibrational case at small frequencies. It is shown that for small frequencies, unexpectateley the localization length is smaller for correlated than for uncorrelated chains.Comment: to be published in PRB, 4 pages, 2 Figure

Synthesis, radiolabelling and in vitro and in vivo evaluation of a novel fluorinated ABP688 derivative for the PET imaging of metabotropic glutamate receptor subtype 5

(E)-3-(Pyridin-2-ylethynyl)cyclohex-2-enone O-(2-(3-18F-fluoropropoxy)ethyl) oxime ([18F]-PSS223) was evaluated in vitro and in vivo to establish its potential as a PET tracer for imaging metabotropic glutamate receptor subtype 5 (mGluR5). [18F]-PSS223 was obtained in 20% decay corrected radiochemical yield whereas the non-radioactive PSS223 was accomplished in 70% chemical yield in a SN2 reaction of common intermediate mesylate 8 with potassium fluoride. The in vitro binding affinity of [18F]-PSS223 was measured directly in a Scatchard assay to give Kd = 3.34 ± 2.05 nM. [18F]-PSS223 was stable in PBS and rat plasma but was significantly metabolized by rat liver microsomal enzymes, but to a lesser extent by human liver microsomes. Within 60 min, 90% and 20% of [18F]-PSS223 was metabolized by rat and human microsome enzymes, respectively. In vitro autoradiography on horizontal rat brain slices showed heterogeneous distribution of [18F]-PSS223 with the highest accumulation in brain regions where mGluR5 is highly expressed (hippocampus, striatum and cortex). Autoradiography in vitro under blockade conditions with ABP688 confirmed the high specificity of [18F]-PSS223 for mGluR5. Under the same blocking conditions but using the mGluR1 antagonist, JNJ16259685, no blockade was observed demonstrating the selectivity of [18F]-PSS223 for mGluR5 over mGluR1. Despite favourable in vitro properties of [18F]-PSS223, a clear-cut visualization of mGluR5- rich brain regions in vivo in rats was not possible mainly due to a fast clearance from the brain and low metabolic stability of [18F]-PSS223

High-resolution nerve ultrasound abnormalities in POEMS syndrome: a comparative study

Background: High-resolution nerve ultrasound (HRUS) has been proven to be a valuable tool in the diagnosis of immune-mediated neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is an important differential diagnosis of CIDP. Until now, there have been no studies that could identify specific HRUS abnormalities in POEMS syndrome patients. Thus, the aim of this study was to assess possible changes and compare findings with CIDP patients. Methods: We retrospectively analyzed HRUS findings in three POEMS syndrome and ten CIDP patients by evaluating cross-sectional nerve area (CSA), echogenicity and additionally calculating ultrasound pattern scores (UPSA, UPSB, UPSC and UPSS) and homogeneity scores (HS). Results: CIDP patients showed greater CSA enlargement and higher UPSS (median 14 vs. 11), UPSA (median 11.5 vs. 8) and HS (median 5 vs. 3) compared with POEMS syndrome patients. However, every POEMS syndrome patient illustrated enlarged nerves exceeding reference values, which were not restricted to entrapment sites. In CIDP and POEMS syndrome, heterogeneous enlargement patterns could be identified, such as inhomogeneous, homogeneous and regional nerve enlargement. HRUS in CIDP patients visualized both increased and decreased echointensity, while POEMS syndrome patients pictured hypoechoic nerves with hyperechoic intraneural connective tissue. Discussion: This is the first study to demonstrate HRUS abnormalities in POEMS syndrome outside of common entrapment sites. Although nerve enlargement was more prominent in CIDP, POEMS syndrome patients revealed distinct echogenicity patterns, which might aid in its differentiation from CIDP. Future studies should consider HRUS and its possible role in determining diagnosis, prognosis and treatment response in POEMS syndrome

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

BACKGROUND AND OBJECTIVES Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates. METHODS We identified patients with acetylcholine receptor antibody-positive (AChR$^{+}$) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding. RESULTS A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR$^{+}$ MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens. DISCUSSION Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR$^{+}$ MG. CLASSIFICATION OF EVIDENCE This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG

Analisa Pondasi Pile Raft Pada Tanah Lunak Dengan Plaxis 2d

Permasalahan penurunan menjadi salah satu masalah yang sering dihadapi para perencana pondasi bangunan dikarenakan oleh kondisi tanah yang lunak. Untuk mengatasi permasalahan yang ada, banyak perencana menggunakan pondasi raft atau pondasi rakit, karena dianggap mampu memberikan faktor keamanan yang memadai dalam menghadapi kegagalan daya dukung ultimate. Namun diperkirakan pondasi raft ini akan mengalami penurunan yang besar. Permasalahan tersebut mungkin dapat berkurang jika adanya penambahan pile pada pondasi raft sehingga menjadi pondasi pile raft. Dengan penambahan pile pada pondasi raft diharapkan perencanaannya mempertimbangkan segi ekonomis. Dengan menggunakan beban merata 6 t/m2, dilakukan penelitian pada pondasi pile raft dengan memvariasikan tebal raft yakni 80 cm, 100 cm, 120 cm dan 140 cm. Untuk panjang pile divariasikan dari panjang 5 m, 7 m, 9 m, 13 m dan 15 m. Analisis penurunan dilakukan dengan menggunakan software Plaxis 2D dan Metode Poulos. Hasil dari penelitian ini menunjukkan bahwa Penambahan jumlah pile pada pondasi raft menghasilkan profil penurunan yang berkurang namun pada suatu keadaan tertentu penambahan pile tidak memberikan kontribusi yang lebih signifikan. Begitupun dengan perhitungan Poulos, pada konfigurasi pile tertentu tidak memberi kontribusi lagi. Sehingga desain yang ekonomis pada penelitian ini adalah dengan menggunakan tebal raft 80 cm dengan panjang pile 13 m dan konfigurasi pile 7x7

Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-Year-Old Children: Results from the GINI-plus Prospective Birth Cohort Study

BACKGROUND: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear. OBJECTIVE: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally. METHODS: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal," "borderline," or "abnormal" according to the subscales "emotional symptoms," "conduct problems," "hyperactivity/inattention," "peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires. RESULTS: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age. CONCLUSIONS: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important

Premature stroke and cardiovascular risk in primary Sjögren's syndrome

IntroductionPrimary Sjögren's syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs). The study aimed to identify specific risk factors for CVD in pSS patients.MethodsPSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease, and carotid plaques. Data were collected by a standardized protocol and review of medical records.Results61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes (p < 0.05), pSS manifestations, in particular vasculitis (p = 0.033) and Raynaud's phenomenon (p = 0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease (n = 12/28, 42.9%), correlations with increased EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.039) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) (p = 0.048) were observed. Age at first cerebrovascular event was 55.2 [48.9–69.6] years. Multivariate analysis confirmed hypertension [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87–7.18, p < 0.001], hypercholesterinemia (OR 3.1, 95% CI 1.63–5.72, p < 0.001), male gender (OR 0.4, 95% CI 0.17–0.78, p = 0.009), Raynaud's phenomenon (OR 2.5, 95% CI 1.28–4.82, p = 0.007), and CNS involvement (OR 2.7, 95% CI 1.00–7.15, p = 0.048) as independent CVD predictors.ConclusionRaynaud's phenomen as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients