Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using Next Generation Sequencing (NGS) for five genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, nine of them novel. In five families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, eight (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-yrs, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies

End-stage kidney disease due to haemolytic uraemic syndrome - outcomes in 241 consecutive ANZDATA Registry cases

Extent: 11p.Background: The aim of this study was to investigate the characteristics and outcomes of patients receiving renal replacement therapy for end-stage kidney disease (ESKD) secondary to haemolytic uraemic syndrome (HUS). Methods: The study included all patients with ESKD who commenced renal replacement therapy in Australia and New Zealand between 15/5/1963 and 31/12/2010, using data from the ANZDATA Registry. HUS ESKD patients were compared with matched controls with an alternative primary renal disease using propensity scores based on age, gender and treatment era. Results: Of the 58422 patients included in the study, 241 (0.4%) had ESKD secondary to HUS. HUS ESKD was independently associated with younger age, female gender and European race. Compared with matched controls, HUS ESKD was not associated with mortality on renal replacement therapy (adjusted hazard ratio [HR] 1.14, 95% CI 0.87-1.50, p = 0.34) or dialysis (HR 1.34, 95% CI 0.93-1.93, p = 0.12), but did independently predict recovery of renal function (HR 54.01, 95% CI 1.45-11.1, p = 0.008). 130 (54%) HUS patients received 166 renal allografts. Overall renal allograft survival rates were significantly lower for patients with HUS ESKD at 1 year (73% vs 91%), 5 years (62% vs 85%) and 10 years (49% vs 73%). HUS ESKD was an independent predictor of renal allograft failure (HR 2.59, 95% CI 1.70-3.95, p < 0.001). Sixteen (12%) HUS patients experienced failure of 22 renal allografts due to recurrent HUS. HUS ESKD was not independently associated with the risk of death following renal transplantation (HR 0.92, 95% CI 0.35-2.44, p = 0.87). Conclusions: HUS is an uncommon cause of ESKD, which is associated with comparable patient survival on dialysis, an increased probability of renal function recovery, comparable patient survival post-renal transplant and a heightened risk of renal transplant graft failure compared with matched ESKD controls.Wen Tang, Janaki Mohandas, Stephen P McDonald, Carmel M Hawley, Sunil V Badve, Neil Boudville, Fiona G Brown, Philip A Clayton, Kathryn J Wiggins, Kym M Bannister, Scott B Campbell and David W Johnso

The interrelation of EU law with inter se international agreements of the EU member states

This thesis examines how EU law interrelates with international agreements concluded between EU Member States inter se when a conflict between their norms can be identified. Chapter One starts by distinguishing between the different types of international agreements that may co-exist with EU law and argues that conflicts between EU law and inter se agreements need to be approached as conflicts of treaty norms on the international plane, using the conflict avoidance techniques and conflict resolution rules of international law. Against this background, Chapter Two examines and discards the premise that EU law constitutes a ‘new legal order’, highlighting the nature of EU law as international law. Chapter Three then examines the position of EU law within international law, identifying EU law as an autonomous sub-system within public international law, in the sense of a broadly conceived ‘self-contained regime’. Chapter Four moves on to define the notion of ‘conflict’ between EU law and inter se agreements and provides the conceptual framework, within which it is to be grasped. Chapter Five explores the available conflict avoidance techniques, identifying two interrelated, yet distinct interpretative methods applicable to the context of this thesis: first, the principle of systemic integration, enshrined in Article 31(3)(c) of the Vienna Convention on the Law of Treaties (VCLT); and second, the principle of a consistent-with-EU-law interpretation of inter se agreements, as a special application of the principle of harmonious interpretation applied in international law. Finally, Chapter Six identifies the rules governing conflict resolution in the interrelation of EU law with inter se agreements: first, Article 59 VCLT on the implicit abrogation of an earlier agreement by the conclusion of a later one between the same contracting parties; second, Article 30 VCLT, to the extent that it codifies the pacta tertiis principle of public international law; and third, the principle of primacy of EU law, which operates as a lex specialis, carving out the lex posterior conflict rule enshrined in Articles 30(3) and 30(4)(a) VCLT.</p

What do Greek physicians know about managing cancer pain?

Background: pain is prevalent in cancer patients. Although the World Health Organization has issued guidelines for treating pain in cancer patients, pain is often not treated optimally. Numerous barriers have been identified that prevent health care professionals from providing effective treatment for pain. The knowledge and attitudes of health care professionals with regard to pain and its impact on the patient are among them. The purpose of the present study was to evaluate knowledge about and attitudes toward cancer pain and its management among Greek oncologists, surgeons, anesthesiologists, and general practitioners. Method: knowledge of the principles and methods of cancer pain treatment was assessed by a questionnaire distributed to a representative sample of 1,200 Greek physicians. Results: the study results highlight very substantial knowledge deficits in the treatment of cancer pain by the evaluated physicians. Conclusions: cancer pain management in Greece is still developing, and the latest knowledge is spreading slowly but steadil

Concurrent Validity of Inertially Sensed Measures during Voluntary Body Sway in Silence and while Exposed to a Rhythmic Acoustic Stimulus: A Pilot Study

Introduction: The effect of rhythmic acoustic stimuli on body sway is of increasing interest due to their positive contribution when training or restoring the control of movement. Inertial sensors show promise as a portable, easier, and more affordable method compared to the force plate &quot;gold standard&quot;concerning the evaluation of postural sway. This study examined the concurrent validity of inertially sensed measures of voluntary body sway against those obtained with a force plate, in silence and while exposed to a rhythmic acoustic stimulus. Methods: Temporal (sway duration and variability) and spatial (trajectory length, variability, range, velocity, and area) body sway variables were extracted using an inertial sensor (at L5) in synchronization with a force plate, during anteroposterior body sway in silence and while exposed to a rhythmic acoustic stimulus (n = 18 young women; two 70-s trials in each condition). Statistics included bivariate correlations between the inertially sensed and the force plate measures, separately, in silence and with a rhythmic acoustic stimulus, as well as for the effect of the rhythmic acoustic stimulus (percentage difference from silence) (p ≤ 0.05, SPSS v25.0). Results: The inertially sensed measures demonstrated good-to-excellent concurrent validity for all temporal and almost all spatial variables, both in silence and with rhythmic acoustic stimulus (r &gt; 0.75, p = 0.000), as well as for the rhythmic acoustic-stimulus effect (r &gt; 0.75, p ≤ 0.05). Conclusion: The inertially sensed measures of the voluntary anteroposterior body sway demonstrated an overall good-to-excellent concurrent validity against those obtained with the force plate &quot;gold standard,&quot;both in the silence and the rhythmic acoustic stimulus conditions, as well as for the rhythmic acoustic-stimulus effect. The findings of this pilot study allow the recommendation of inertial sensing for the evaluation of postural control alterations when exposed to rhythmic acoustic stimuli, a condition of increasing interest due to the positive contribution of such stimuli when training or restoring the control of movement. © 2020 The Author(s)

Nurses&apos; attitudes toward truthful communication with patients with cancer: A Greek study

The purpose of this study was to examine Greek nurses&apos; attitudes toward truth-telling practices when working with cancer patients and their psychological status regarding the difficulties they face in their day-to- day communication with these patients. A self-administered questionnaire composed of 19 questions, including both multi-item scales and single-item measures, was designed for the study. For this study, 200 nurses were asked to participate, of whom 148 (74%) completed and returned the questionnaire. The questionnaire is self-administered, formulated after a thorough review of the relevant literature. The pretesting was carried out using the alpha model of reliability and the Cochran Chi Square test (Q-test), which was 545.46 (P &lt; .0001) and showed a Cronbach alpha coefficient of 0.7148. A large percentage of the respondents (75.7%) believe that only some patients with cancer should be told the truth of their diagnosis and prognosis, although a larger percentage (89.1%) believe that the truth should be told to the relatives. Most of the respondents (66.2%) reported that is difficult to engage in open communication with the patients, because their academic education did not sufficiently train them in communication skills. Although 83.78% of the nurse respondents do not reveal that the disease is incurable, 86 (58.1%) believe that only the patient&apos;s physician should reveal the truth. These results indicate that although many Greek nurses believe that the patients should be informed and know their condition, lack of training in communication skills is a major obstacle to achieving this. Finally, this self-assessment questionnaire may provide acceptable and valid assessment of Greek nurses&apos; perceptions and attitudes on truth telling

Use of TTS fentanyl as a single opioid for cancer pain relief: A safety and efficacy clinical trial in patients naive to mild or strong opioids

Background. Up to now, a transdermal therapeutic system (TTS) of fentanyl has been applied to cancer patients on opioid analgesics previously treated with mild opioids or morphine. The aim of this study was to investigate the efficacy and safety of TTS fentanyl (patch) administration as an analgesic to patients treated with opioid analgesics for moderate-to-severe cancer pain, with immediate-release oral morphine only as rescue medication. The prior analgesic medication of the patients did not include mild or strong opioids. Methods., The study group consisted of 113 patients (54 men and 59 women; age range: 21-87 years, mean +/- SD 61.3 +/- 14.84 years) with undertreated chronic cancer pain. The study period was 42 days. The patients were hospitalized for the first 3 days of the study; thereafter they were transferred to their home for the rest of the study. Daily cards were completed, noting their pain score (0-10 VAS), nausea, vomiting, constipation, skin reactions, dizziness or any other complaints. Vital signs were also recorded. Data assessments were made at baseline, on days 1, 2 and 3 (during hospitalization) and thereafter on days 7, 14, 21, 28, 35, and 42 after hospital discharge. The initial TTS fentanyl delivery rate was chosen depending on the patient’s analgesic requirements. All patients were given an oral morphine solution (5-10 mg), every 4-6 h, for the first 12 h, as rescue medication. Results: Baseline pain score was between 6 and 10 (mean SD 7.1 +/- 1.7). The initial TTS fentanyl delivery rate was between 25 and 50 mug/h (mean +/- SD 36.5 +/- 15.7). On day 3, 95 patients (84%) reported a pain score less than or equal to3 (mean +/- SD 0.5 +/- 0.8), 14 patients (12.4%) a pain score of 4 and 4 patients (3.5%) of 5-8. No adverse effects suggesting the discontinuation of the study were reported. From day 7 until the completion of the study, the mean pain score was between 1.3 and 0.16 while the TTS fentanyl delivery rate on day 42 was between 25 and 400 mug/h (mean +/- SD 122.1 +/- 81.2 mug/h). Conclusion: Analgesic treatment with TTS fentanyl used as a single opioid is effective and safe for cancer pain relief, given that is cautiously applied, in patients requiring strong opioid analgesics even if they were naive to strong or mild opioids. Copyright (C) 2002 S. Karger AG, Basel

Physical Modeling of the Ancient Greek Wind Musical Instrument Aulos: A Double-Reed Exciter Linked to an Acoustic Resonator

We present a simulation method for the auralization of the ancient Greek double-reed wind instrument Aulos. The implementation is based on Digital Signal Processing and physical modeling techniques for the instrument&apos;s two parts: the excitation mechanism and the acoustic resonator with toneholes. Single-reeded instruments are in-depth studied firstly because their excitation mechanism is the one used in a great amount of modern wind-reed instruments and secondly because the physics governing the phenomena is less complicated than the double-reeded instruments. We here provide a detailed model of a system comprised of a double-reed linked to an acoustic resonator with toneholes to sonify Aulos. We validate our results by comparing our method&apos;s synthesized signal with recordings from a replica of Aulos of Poseidonia built in our lab. The comparison showed that the fundamental frequencies and the first three odd harmonics of the signals differ 6, 5, 3, and 2 cents on average, respectively, which is below the Just Noticeable Difference threshold. © 2013 IEEE