Shift rostering using decomposition: assign weekend shifts first

This paper introduces a shift rostering problem that surprisingly has not been studied in literature: the weekend shift rostering problem. It is motivated by our experience that employees’ shift preferences predominantly focus on the weekends, since many social activities happen during weekends. The Weekend Rostering Problem (WRP) addresses the rostering of weekend shifts, for which we design a problem specific heuristic. We consider the WRP as the first phase of the shift rostering problem. To complete the shift roster, the second phase assigns the weekday shifts using an existing algorithm. We discuss effects of this two-phase approach both on the weekend shift roster and on the roster as a whole. We demonstrate that our first-phase heuristic is effective both on generated instances and real-life instances. For situations where the weekend shift roster is one of the key determinants of the quality of the complete roster, our two-phase approach shows to be effective when incorporated in a commercially implemented algorithm

Healthy aims: developing new medical implants and diagnostic equipment

Healthy Aims is a €23-million, four-year project, funded under the EU’s Information Society Technology Sixth Framework program to develop intelligent medical implants and diagnostic systems (www.healthyaims.org). The project has 25 partners from 10 countries, including commercial, clinical, and research groups. This consortium represents a combination of disciplines to design and fabricate new medical devices and components as well as to test them in laboratories and subsequent clinical trials. The project focuses on medical implants for nerve stimulation and diagnostic equipment based on straingauge technology

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac-derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80(hi)CD11b(lo) primitive macrophages and Ly6C(hi)CD11b(hi) fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF-deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life

Expert consensus recommendations on the cardiogenetic care for patients with thoracic aortic disease and their first-degree

Background: Thoracic aortic aneurysm (TAA) is a potentially life-threatening disorder with a strong genetic component. The number of genes implicated in TAA has increased exponentially over the last decade. Approximately 20% of patients with TAA have a positive family history. As most TAA remain asymptomatic for a long time, screening of at risk relatives is warranted to prevent complications. Existing international guidelines lack detailed instructions regarding genetic evaluation and family screening of TAA patients. We aimed to develop a consensus document to provide medical guidance for all health care professionals involved in the recognition, diagnosis and treatment of patients with thoracic aortic disease and their relatives. Methods: A multidisciplinary panel of experts including cardiologists, cardiothoracic surgeons, clinical geneticists and general practitioners, convened to review and discuss the current literature, guidelines and clinical practice on genetic testing and family screening in TAA. Results: There is a lack of high-quality evidence in the literature. This consensus statement, based on the available literature and expert opinions, summarizes our recommendations in order to standardize and optimize the cardiogenetic care for patients and families with thoracic aortic disease. In particular, we provide criteria to identify those patients most likely to have a genetic predisposition, and discuss the preferred modality and frequency of screening in their relatives. Conclusions: Age, family history, aortic size and syndromic features determine who is advised to have genetic testing as well as screening of first-degree relatives. There is a need for more prospective multicenter studies to optimize current recommendations

No clinically relevant difference in patient-reported outcomes between the direct superior approach and the posterolateral or anterior approach for primary total hip arthroplasty:analysis of 37,976 primary hip arthroplas-ties in the Dutch Arthroplasty Registry

Background and purpose — The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods — In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were mea-sured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the associa-tion between surgical approach and PROMs over time. Results — From baseline to 3 and 12 months, improve-ments for NRS pain scores, EQ-5D, and OHS were com-parable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (–0.2, 95% confidence interval [CI] –2.4 to 1.9) and between DSA and DAA (–1.7, CI –3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved –2.8 points (CI –4.9 to –0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (–1.0, CI –3.2 to 1.1). Conclusion — Our study showed no clinically meaning-ful differences between the DSA and either PLA or DAA.</p

Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) $(p = 8.8×10^{−7} and p = 1.5×10^{−6}$ respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels $(p = 13.5×10^{−12})$. The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report

No clinically relevant difference in patient-reported outcomes between the direct superior approach and the posterolateral or anterior approach for primary total hip arthroplasty:analysis of 37,976 primary hip arthroplas-ties in the Dutch Arthroplasty Registry

Background and purpose — The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods — In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were mea-sured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the associa-tion between surgical approach and PROMs over time. Results — From baseline to 3 and 12 months, improve-ments for NRS pain scores, EQ-5D, and OHS were com-parable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (–0.2, 95% confidence interval [CI] –2.4 to 1.9) and between DSA and DAA (–1.7, CI –3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved –2.8 points (CI –4.9 to –0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (–1.0, CI –3.2 to 1.1). Conclusion — Our study showed no clinically meaning-ful differences between the DSA and either PLA or DAA.</p

Systematic clinical approach for diagnosing upper limb tremor

Tremor is the most common movement disorder worldwide, but diagnosis is challenging. In 2018, the task force on tremor of the International Parkinson and Movement Disorder Society published a consensus statement that proposes a tremor classification along two independent axes: a clinical tremor syndrome and its underlying aetiology. In line with this statement, we here propose a stepwise diagnostic approach that leads to the correct clinical and aetiological classification of upper limb tremor. We also describe the typical clinical signs of each clinical tremor syndrome. A key feature of our algorithm is the distinction between isolated and combined tremor syndromes, in which tremor is accompanied by bradykinesia, cerebellar signs, dystonia, peripheral neuropathy or brainstem signs. This distinction subsequently informs the selection of appropriate diagnostic tests, such as neurophysiology, laboratory testing, structural and dopaminergic imaging and genetic testing. We highlight treatable metabolic causes of tremor, as well as drugs and toxins that can provoke tremor. The stepwise approach facilitates appropriate diagnostic testing and avoids unnecessary investigations. We expect that the approach offered in this article will reduce diagnostic uncertainty and increase the diagnostic yield in patients with tremor

Rare inborn errors of metabolism with movement disorders:a case study to evaluate the impact upon quality of life and adaptive functioning

Background: Inborn errors of metabolism (IEM) form an important cause of movement disorders in children. The impact of metabolic diseases and concordant movement disorders upon children's health-related quality of life (HRQOL) and its physical and psychosocial domains of functioning has never been investigated. We therefore conducted a case study on the HRQOL and development of adaptive functioning in children with an IEM and a movement disorder. Methods: Children with co-existent IEM and movement disorders were recruited from paediatric outpatient clinics. We systematically collected clinical data and videotaped examinations. The movement disorders were diagnosed by a panel of specialists. The Pediatric Quality of Life Inventory 4.0 and the Vineland Adaptive Behavior Scale were used to assess the HRQOL and adaptive functioning, respectively. Results: We recruited 24 children (10 boys, mean age 7y 5 m). Six types of movement disorders were recognised by the expert panel, most frequently dystonia (16/24), myoclonus (7/24) and ataxia (6/24). Mean HRQOL (49.63, SD 21.78) was significantly lower than for other chronic disorders in childhood (e.g. malignancy, diabetes mellitus, rheumatic disease, psychiatric disorders; p Conclusions: A broad spectrum of movement disorders was seen in patients with IEM, although only five were receiving treatment. The overall HRQOL in this population is significantly reduced. Delay in adaptive functioning, most frequently seen in relation to activities of daily living, and the severity of the movement disorder contribute to this lower HRQOL. We plead for a greater awareness of movement disorders and that specialists should be asked to diagnose and treat these wherever possible

Transient parkinsonism in isolated extrapontine myelinolysis

Extrapontine myelinolysis (EPM) is a rare cause of parkinsonism. In this case report, we describe a 63-year-old woman with parkinsonism due to EPM after correction of hyponatremia. During a 4-year follow-up, both the clinical features of parkinsonism and the changes on magnetic resonance imaging resolved. Parkinsonism due to EPM should be recognized as it has a good prognosis