Search

The Robot Operating System 2 (ROS 2) is the second generation of ROS representing a step forward in the robotic framework. Several new types of nodes and executor models are integral to control where, how, and when information is processed in the computational graph. This paper explores and benchmarks one of these new node types -- the Component node -- which allows nodes to be composed manually or dynamically into processes while retaining separation of concerns in a codebase for distributed development. Composition is shown to achieve a high degree of performance optimization, particularly valuable for resource-constrained systems and sensor processing pipelines, enabling distributed tasks that would not be otherwise possible in ROS 2. In this work, we briefly introduce the significance and design of node composition, then our contribution of benchmarking is provided to analyze its impact on robotic systems. Its compelling influence on performance is shown through several experiments on the latest Long Term Support (LTS) ROS 2 distribution, Humble Hawksbill., Comment: IEEE Robotics and Automation Letters, 2023

Background and importance Patients with chronic kidney disease (CKD) are often characterised by the concomitance of multimorbidity, which could cause complex drug prescriptions that lead to a higher risk of incorrect administration and serious drug–drug interactions (DDIs) and potentially inappropriate medications (PIMs). According to national recommendation No17 of the national health system (NHS), these patients need appropriate attention: a multidisciplinary team (clinical pharmacists–clinician–nurse) should systematically re-evaluate pharmacological therapies to simplify/harmonise treatments and increase patient adherence. Aim and objectives The aim of this study was to improve a method to analyse pharmacological therapies, identify incorrect prescriptions and simplify therapies. Material and methods The chosen method requires that the clinical pharmacist in the nephrological team collaborates to analyse 231 therapies of patients, is in charge of the advanced renal disease clinic, using an already identified information and communication technology (ICT) tool.1 Drugs, classified by anatomical therapeutic chemical class (ATC), and dosage units (DU) were counted and DDIs were investigated. PIMs and dangerous drugs were identified by Beers criteria and STOPP criteria. Results 2311 drugs and 2695 DU were counted. Each patient was receiving 10±3.1 different medicines, corresponding to 12.1±8.1 DU/day. 91% of patients were taking 5 or more DU/day and 59.3% at least 10. Stratifying drugs by ATC class identified the following: 644 prescriptions for C02-antihypertensives class, 184 for M04-gout preparations, 135 for C10-lipid modifying agents and 218 for B03-antianaemic preparations. 64% of patients (139) used gastroprotectors, especially proton pump inhibitors (PPIs). 3 DDIs, of 289 detected, were considered contraindicated and potentially serious, and were due to antipsychotic drugs. Drugs most responsible for DDIs were: cardioaspirin, PPIs, angiotensin receptor blockers and diuretics. 975 (4.2±2.2 per patient) and 571 (2.4±1.7 per patient) inappropriate drugs were identified according to STOPP criteria and Beers criteria, respectively. Conclusion and relevance Polypharmacy is associated with a high incidence of DDIs and an increased risk of mortality and hospitalisation. The use of the ICT tool and the clinical pharmacist who bring their contribution in terms of pharmacological and pharmacokinetic knowledge have significantly contributed to the improvement in prescriptive appropriateness and minimised the risk of adverse events. References and/or acknowledgements Critical analysis of the information and communication technologies’ (ICT) tools most used in clinical practice by the pharmacist. Masucci S, Cerutti E, Riba M, Gasco AL (EAHP Congress 2019). Conflict of interest No conflict of interest

Background and Aims Post transplantation anaemia (PTA) is a common finding in kidney transplant patients, with reported prevalence ranging from 25 to 40%, and it is associated with adverse outcomes for the kidney allograft and the recipient. The pathogenesis of PTA is multifactorial, including iron deficiency, reduced graft function, untoward effects of drugs (immunosuppressants, ACE-I and ARB), folic acid and vitamin B12 deficiency, inflammatory states. Ferric carboxymaltose (FCM) reportedly improved haemoglobin (Hb) levels and replenished depleted iron stores in various populations of patients with iron-deficiency anaemia, but there are few data about its use in PTA. In this study we evaluated the effectiveness and tolerability of high intravenous doses of FCM (500 mg) for the treatment of iron deficiency and anaemia in patients with kidney transplant. Method Absolute iron deficiency was considered as transferrin saturation (TSAT) less than 20% with ferritin levels below 100 µg/L. Anaemia was defined as Hb Out of 101 patients with kidney transplant, 56 presented with absolute iron deficiency (59±13 years old, M/F=0.95, 8±4.6 years of transplantation; serum creatinine 1.45±0.64 mg/dL): of these, 40 patients had anaemia (7 were also taking ESAs) and 16 had normal Hb levels. The 16 patients with absolute iron deficiency and normal Hb were not prescribed iron supplements, fearing of causing erythrocytosis, whereas 36 of 40 patients with anaemia and iron deficiency were given FCM 500 mg, as i.v. infusion for 30 minutes. Hb, ferritin and TSAT were assayed either before and 45-60 days after FCM supplementation, which was repeated if Hb levels were less than 0.5 g/dL below the normal value. Data were reported as mean±SD. Results Among the 56 patients with absolute iron deficiency, there were not any significant differences in serum levels of folic acid and vitamin B12 between those with and without anaemia (p=ns). After the first dose of FCM, in 36 patients with iron deficiency and anaemia, ferritin levels increased from 55±69 ng/mL to 111±107 ng/mL (p Out of the 17 patients still showing anaemia after the first FCM dose, 10 had Hb levels less than 0.5 g/dL below the normal value and were given a second dose of FCM. In this subset, Hb level increased on average from 11.4±0.5 g/dL to 12±0.9 g/dL (p After the FCM course, in 2 out of 7 patients ESAs were discontinued, whereas in 3 patients their doses were reduced and in 2 patients remained unchanged. Only one patient had an adverse effect during FCM infusion, namely, a transient skin flushing on her face during the second dose, which immediately remitted when the infusion was interrupted. Conclusion In patients with PTA and absolute iron deficiency, single or repeated doses of 500 mg of i.v. FCM were effective in improving Hb levels, well tolerated and reduced the need for ESAs. Of 56 patients with kidney transplant and absolute iron deficiency, 16 (28%) had normal Hb levels. We did not treat such subjects, fearing of causing erythrocytosis. However, given that iron deficiency may affect negatively both heart and muscle metabolism, what is the best management of iron deficiency in transplanted patients without anaemia is still an open question.

Background and Aims Autosomal dominant PKD determines formation of multiple cysts predominantly in the kidneys and usually becomes symptomatic during adulthood and can lead to renal failure. In contrast, in autosomal recessive PKD cysts occur in both the kidneys and the liver and usually presents an earlier onset. Obtaining genetic diagnosis is important to confirm clinical diagnosis and is required before treating with vasopressin 2 receptor blockers, which are the only drugs known to slow down the disease. Furthermore, in the case of kidney transplant from a living family member it is essential to exclude the presence of the mutation in the donor. We used clinical exome sequencing to provide genetic diagnosis to a cohort of patients with a clinical suspicion of PKD. Method 175 patients were referred to the Immunogenetics and Transplant Biology Service of the Turin University Hospital through a network of nephrology centers operating in the Piedmont region. Some patients were referred following genetic counseling. All patients signed an informed consent and the referring physicians provided relevant clinical data. DNA from eligible patients was extracted, checked for integrity, quantified and used for library preparation. A clinical exome sequencing (CES) kit by Illumina was used, allowing the analysis of 6,700 clinically relevant genes. Results Out of the 175 recruited patients eligible for CES, 38 (21.7%) had a clinical suspicion or diagnosis of PKD, with 50% of them presenting family history. The majority of the cohort was represented by male subjects (60.5%) and included both children (34.2%) and adults. The analytical approach was based on initial analysis of genes responsible for PKD (PKD1, PKD2 and PKHD1). If no mutation could be identified, analysis was then extended to a panel of 99 genes responsible for ciliopathies. This approach led to the identification of causative variants in 33/38 (86.8%) of the PKD cohort, while no variant could be identified in 5/38 patients. In 5/33 (15.2%) patients, mutations were inconclusive as found in heterozygosity in genes known to have an autosomal recessive mode of inheritance, while 27/33 (81.8%) were in line with the initial clinical suspicion/diagnosis. Of these, the majority was represented by missense mutations (12), followed by frameshift and nonsense mutations (6 each) and 3 splicing variants. As expected, the majority of mutations were found in PKD1 17/27 (63%), PKD2 3/27 (11.1%) and PKHD1 2/27 (7.4%). In these two latter patients, variants were found as compound heterozygosity. We also found mutations in other genes known to cause cysts, including TSC2 and CPT2. Of note, in 7 patients carrying PKD1 mutations, we found a second variant in PKD1 or PKHD1. Interestingly, when looking at patients characterized by kidney failure but lacking a clinical suspicion at recruitment or diagnosed with other phenotypes (66/175), we found variants in PKD1 and in PKD2 in 11 patients (9 and 2, respectively). Of all identified variants in PKD1, PKD2 and PKHD1 genes, 17.6% were annotated as pathogenic (C5), 41.2% were likely pathogenic (C4) and 41.2% were variants of unknown significance (C3). 19 variants in these genes were not previously reported. All the variants found in genes responsible for PKD were validated and confirmed by Sanger sequencing. Family segregation studies are ongoing. Finally, it is worth mentioning that in a portion of cases (5/38) with clinical and phenotypic features of PKD, supported also by a positive family history, we could not detect mutations in causative genes. These results may be explained by the presence of intronic variants, in line with data reported in literature. Conclusion These results demonstrate that CES may be applied to PKD patients to identify causative variants during their routine diagnostic flow. Furthermore, CES may be a useful tool to detect mutations in PKD-related genes in patients with undiagnosed diseases, considering its rapidly decreasing costs.

Background Most of the patients with advanced chronic kidney disease (ACKD) are fragile due to multimorbidity and associated polypharmacy. For this kind of population, polypharmacy and potentially inappropriate prescribing are common problems that impact both on patient compliance and on drugs cost for the National Health System (NHS). For therapy with high pill-burden medication reconciliation (MR), supported by Information and Communication Technology’s (ICT) instrument, is one of the most effective tools in preventing over/under/mis-prescription and drug interaction (DI), and the clinical pharmacist is the suitable figure to support the clinician in promoting the appropriateness of therapies in the transition of care. Purpose The aim was to estimate compliance and the economic impact of a multidisciplinary clinical-pharmacist-led MR process in patients with ACKD. Material and methods Selection and implementation of ICT tool; identification of mistaken prescription with indicators of appropriateness, such as START/STOPP and Beers criteria; proposal and evaluation of new therapies with the nephrologist; and estimation of therapies costs pre- and post-MR. Results The identified ICT tool was the acknowledged platform NavFarma Suite, the same as used in two other regional projects with the purpose of creating a path between admission and discharge therapy. MR was conducted in 92 patients. The clinical pharmacist identified 265 DI, five classified as contraindicated and 260 as major, with a level of evidence equal to 52% excellent, 16% good and 32% discrete. 3.75% of therapies analysed were considered inappropriate. Cost analysis: the average cost of a single treatment for the patient was €704 charged to the NHS and €102 charged to the patient. The MR allowed a cost reduction of 4% for the NHS and of 37% for the patient. Conclusion The project demonstrates that MR is one of the most appropriate methodologies to correct prescription errors, improve patient compliance and carry out a more effective model for pharmaceutical expenditure management. Technology and multidisciplinary summarises more suitable the innovation of the proposed model, in which a new figure, the clinical pharmacist, integrates the medical and nursing team by bringing his contribution in terms of pharmacological and pharmacokinetic knowledge and stimulates the critical evaluation of the therapeutic choices and of the data processed through the use of an accurate ICT tool. References and/or acknowledgements No conflict of interest.

Primary hyperparathyroidism (PHPT) may favor nephrolithiasis mainly through an increase in calcium and phosphate urinary excretion. Cinacalcet exhibits good efficacy to control hypercalcemia in PHPT, but it is not so far known whether it might be a useful tool to prevent stone recurrences. Of 67 patients with PHPT and recurrent nephrolithiasis, 55 underwent parathyroidectomy (PTX) and 12, not eligible to PTX, were prescribed Cinacalcet. All the patients were evaluated for mineral metabolism, including estimation of state of saturation for calcium oxalate (CaOx) and brushite (bsh), both at baseline and after either PTX or Cinacalcet. PTX compared to baseline reduced PTH (4617 vs 15786 pg/mL, p0.01), calcemia (9.40.5 vs 11.30.9 mg/dL, p0.01), calciuria (3.62.3 vs 9.24.5 mmol/24h, p0.01), phosphaturia (18.47.1 vs 21.99.9 mmol/24h, p0.05), CaOx (4.73.9 vs 9.86.8, p0.01) and bsh (1.10.9 vs 3.22.2, p0.01). Cinacalcet decreased both PTH (13379 vs 17187 pg/mL, p0.05) and calcemia (9.70.6 vs 11.20.8 mg/dL, p0.001), whereas no change was seen in calciuria (7.42.2 vs 7.42.4 mmol/24h, p=ns), phosphaturia (21.97.3 vs 23.06.5 mmol/24h, p=ns), CaOx (6.92.7 vs 5.42.5, p=ns) and bsh (1.71.1 vs 1.31.3, p=ns). We conclude that in patients with PHPT, PTX is able to decrease the risk for crystallization of calcium salts, whereas calcimimetic Cinacalcet did not. Therefore, in patients with PHPT complicated with nephrolithiasis only PTX can improve urine biochemistries thereby reducing the risk for recurrent calcium stone disease.

Background: Unfractionated heparin (UFH) is the standard anticoagulant in regular dialysis treatments (RDTs), despite the fact that it may induce thrombocy- topenia, dyslipidemia, allergy and osteoporosis. Der- matan sulfate (DS) selectively inhibits thrombin, does not inhibit F-Xa and does not interfere with platelets (PLTS). Here we described an original protocol for the use of DS as anticoagulant in RDT and compared its effects with those of UFH. Methods: In 102 patients, 7,254 RDTs were performed using DS for anticoagulation (DS-phase) and 5,707 with UFH (UFH-phase). DS was supplied as initial bo- lus (80 ± 12 mg) and continuous infusion (14 ± 7 mg/ hour). With UFH, the initial bolus was 1,475 ± 141 IU and continuous infusion 576 ± 349 IU/hour. Activated par- tial thromboplastin time and its ratio were measured at least monthly, both before (pre-RDT APTT ratio) and af- ter (post-RDT APTT ratio) RDT sessions. With 41of 102 patients, both DS and UFH doses were not changed during study phases (stable patients). In this subset, the coefficient of variation (CV) of all pre-RDT APTT ratio and post-RDT APTT ratio values was calculated. Results: In DS and UFH phases, post-RDT APTT ra- tio increased by 61% and 50%, respectively, by com- parison with pre-RDT APTT ratio (p

The glutamate transporter excitatory amino acid carrier (EAAC1/EAAT3) mediates the absorption of dicarboxylic amino acids in epithelial cells as well as the uptake of glutamate from the synaptic cleft. Its cell-surface density is regulated by interaction with accessory proteins which remain to be identified. We detected a consensus sequence for interaction with post-synaptic density-95/Discs large/Zonula occludens (PDZ) proteins (-SQF) and a tyrosine-based internalization signal (-YVNG-) in the C-terminus of EAAC1, and investigated their role in the transporter localization. We demonstrated that PDZ interactions are required for the efficient delivery to and the retention in the plasma membrane of EAAC1 and we identified PDZK1/NHERF3 (Na+/H+-exchanger regulatory factor 3) as a novel EAAC1 interacting protein. Expression of PDZK1 in Madin-Darby canine kidney (MDCK) cells tethered EAAC1 to filopodia and increased its surface activity. Removal of the PDZ-target motif promoted the EAAC1 binding to α-adaptin and clathrin and the transporter internalization in endocytic/degradative compartments. This defect was largely prevented by hypertonic treatment or overexpression of the dominant-negative µ2-W421A-subunit of AP-2 clathrin-adaptor. The rate of transporter endocytosis was attenuated following tyrosine mutagenesis in the internalization signal, thus indicating that this motif can regulate the transporter endocytosis. We suggest that EAAC1 density is controlled by balanced interactions with PDZK1 and adaptor protein 2 (AP2): the former promotes the transporter expression at the cell surface, and the latter mediates its constitutive endocytosis.