PENGARUH TEKANAN KETAATAN DAN KOMPLEKSITAS TUGAS TERHADAP AUDIT JUDGMENT (Survey Terhadap Lima Kantor AkuntanPublik di Kota Bandung)

ABSTRAK Seperti yang kita ketahui bahwa seorang auditor dalam melakukan tugasnya membuat audit judgment dipengaruhi banyak faktor, baik bersifat teknis dan non teknis. Salah satu faktor non teknis adalah aspek perilaku individual. Aspek perilaku individu, sebagai salah satu faktor yang banyak mempengaruhi pembuatan audit judgment. Pada penelitian ini ada beberapa faktor yang mempengaruhi audit judgment yaitu tekanan ketaatan dan kompleksitas tugas. Dalam penelitian ini penullis ingin mengetahui sejauh mana “tekanan ketaatan dan kompleksitas tugas terhadap audit judgment”. Sedangkan tujuan dari penelitian ini adalah untuk mengetahui dan mempelajari tekanan ketaatan dan kompleksitas tugas terhadap audit judgment. Hipotesis yang diuji dalam penelitian ini adalah “ jika tekanan ketaatan dan kompleksitas tugas baik, maka audit judgment akan meningkat ( baik pula)”. Hipotesis ini berdasarkan asumsi bahwa tekanan ketaatan dan kompleksitas tugas berpengaruh terhadap audit judgment.dalam penelitian ini penulis menggunakan metode deskriptif asosiatif dengan pendekatan survey dan tes statistik. Penelitian ini terdiri dari atas variabel X1 dan X2 dan audit judgment sebagai veriabel Y atau variabel independen. Uji statistik dilakukan dengan mengolah data dari hasil jawaban kuesioner. Dalam penelitian ini, peulis menyebarkan angket kepada 5 Kantor Akuntan Publik di Kota Bandung khusunya untuk para auditor. Pengumpulan data dilakukan dengan cara penyebaran kuesioner yang telah diuji validitasnya dan reabilitasnya. Penelitian ini dilakukan di 5 KAP di Kota Bandung. Pengambilan sampel ini menggunakan purposive sampling berukuran 28 orang responden. Untuk uji hipotesis penelitian, penulis melakukannya dengan uji t untuk masing-masing variabel X1,X2, dan Y. Dari hasil uji tHitung tekanan ketaatan terhadap audit judgment tHitung =4,178>ttabel = 1.705 kompleksitas tugas terhadap audit judgment 5 tHitung = 3.364 > ttabel = 1,705. Maka, dari hasil uji hipotesis tersebut penulis menyimpulkan bahwa hipotesis penelitian diterima (Ho ditolak, Ha diterima) artinya terdapat pengaruh antara terkanan ketaatan terhadap audit judgment dan kompleksitas tugas terhadap audit judgment Untuk mencari besarnya pengaruh Tekanan ketaatan dan Kompleksitas Tugas terhadap Audit Judgment secara simultan penulis melakukannya dengan uji f dengan koefisien determinasi (KD). Dari hasil uji fhitung dan > f table yaitu 16,182>3,370. Kata kunci : Tekanan Ketaatan dan Kompleksitas tugas Terhadap Audit Judgmen

The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Biobanking science applied to patient specific stem cells and biomarkers for Parkinson's disease research

Biomedical research aims to understand the pathological and pathophysiological mechanisms that cause disease. Neurodegenerative diseases, such as Parkinson’s disease (PD), are major contributors to the burden of disease across the globe. PD is an age-related, progressive neurodegenerative disease. The pathological hallmarks are a selective loss of dopaminergic neurons from the substantia nigra in conjunction with the presence of protein aggregates involving α-synuclein in the residual neurons. Cystatin C expression has been shown to become upregulated in brain injuries, neurological disorders and in animal models of neurodegenerative states, which suggests it could play a part in neurodegenerative disorders. The main function of this primarily secreted protein is the inhibition of cysteine proteases. Various tools are available to researchers to study diseases, ranging from animal models, human biospecimens and human in vitro models. Regardless of the model selected, reproducibility is crucial to ensure meaningful research. To maximise the quality of biomedical research, biobanks work to ensure the biospecimens they issue are compromised as little as possible as a consequence of the unavoidable preanalytical variables occurring during their collection, processing and storage. The scientific discipline that studies preanalytical variables and how they affect biospecimens is called biospecimen science. In this thesis, biospecimen science was applied to patient specific stem cells and cystatin C in the scope of PD research. A standardized research-grade human induced pluripotent stem cell (iPSC) workflow was established for use as an in vitro PD model, which encompasses both iPSC generation and cryostorage. Controlled-rate freezing of iPSCs using three different dimethyl sulfoxide-based cryosolutions containing ice recrystallization inhibitors was evaluated and optimized to achieve efficient iPSC cryopreservation. A double, indirect sandwich ELISA was established to quantify the concentration and the degradative state of secreted cystatin C. The ELISA was validated using well-defined and standardized cerebrospinal fluid (CSF) biospecimens, then applied as a tool to retrospectively identify CSF biospecimens that had been stored in suboptimal conditions. Secreted cystatin C was quantified and compared in blood derivatives (plasma and serum) and in the culture media of derived models (iPSCs, neuroepithelial stem cells and midbrain organoids) from three idiopathic PD patients and age-matched healthy controls. The standardized in vitro PD models, novel quality control and cryopreservation methods not only demonstrate the critical importance of preanalytical standardization but open the way to future biomedical research

In Vitro Comparative Study of Platelets Treated with Two Pathogen-Inactivation Methods to Extend Shelf Life to 7 Days

Background and Objectives: Since 2015, platelet products have been pathogen-inactivated (PI) at the Luxemburgish Red Cross (LRC) using Riboflavin and UV light (RF-PI). As the LRC should respond to hospital needs at any time, platelet production exceeds the demand, generating a discard rate of 18%. To reduce this, we consider the extension of storage time from 5 to 7 days. This study’s objective was to evaluate the in vitro 7-day platelet-storage quality, comparing two PI technologies, RF-PI and amotosalen/UVA light (AM-PI), for platelet pools from whole-blood donations (PPCs) and apheresis platelets collected from single apheresis donation (APCs). Materials and Methods: For each product type, 6 double-platelet concentrates were prepared and divided into 2 units; one was treated with RF-PI and the other by AM-PI. In vitro platelet-quality parameters were tested pre- and post-PI, at days 5 and 7. Results: Treatment and storage lesions were observed in PPCs and APCs with both PI methods. We found a higher rate of lactate increase and glucose depletion, suggesting a stronger stimulation of the glycolytic pathway, a higher Annexin V binding, and a loss of swirling in the RF-PI-treated units from day 5. The platelet loss was significantly higher in the AM-PI compared with the RF-PI units. Conclusions: Results suggest that RF-PI treatment has a higher deleterious impact on in vitro platelet quality compared to AM-PI, but we observed higher loss of platelets with AM-PI due to the post-illumination amotosalen adsorption step. If 7-day storage is needed, it can only be achieved with AM-PI, based on our quality criteria

A cystatin C cleavage ELISA assay as a quality control tool for determining sub-optimal storage conditions of cerebrospinal fluid samples in alzheimer's disease research

Background: An N-terminal octapeptide cleavage of the cystatin C protein was discovered by mass spectrometry when cerebrospinal fluid (CSF) was stored at -20°C for 3 months, which did not occur when CSF was stored at -80°C. Objective: The aim was to develop an immunoassay as quality assessment tool to detect this -20°C cleavage of cystatin C in CSF and support Alzheimer's disease research. Methods: A specific monoclonal antibody and a double indirect sandwich ELISA were developed: one assay quantifies the octapeptide uncleaved protein specifically and the other quantifies the total cystatin C present in the biological fluid (both cleaved and uncleaved forms). The ratio of these concentrations was calculated to assess the extent of cleavage of cystatin C. The novel ELISA was validated and applied in a short-term (up to 4 weeks) and mid-term (up to one year) stability study of CSF stored at 4°C, -20°C, -80°C, and liquid nitrogen. Impact of freeze-thaw cycles, adsorption, and protease inhibitors were tested. Results: The ratio of truncated protein was modified following -20°C storage and seemed to reach a plateau after 6 months. The ratio was impacted neither by freeze-thaw cycles nor adsorption. The -20°C specific cleavage was found to be protease related. Conclusion: Using this novel double indirect sandwich ELISA, absolute levels of the total and uncleaved cystatin C and the ratio of truncated cystatin C can be measured. This assay is an easily applicable tool which can be used to confirm that CSF biospecimen are fit-for-purpose for Alzheimer's disease research