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Background Waning of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates the diagnosis of past infection. The durability of T-cell memory against SARS-CoV-2 remains unclear, and most current T-cell protocols are unsuited for large-scale automation. Methods Whole-blood samples from 31 patients with verified past coronavirus disease 2019 (COVID-19) and 46 controls, of whom 40 received COVID-19 vaccine, were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon γ in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti–receptor-binding domain S1-IgG. Results Induction of interferon γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (area under the receiver operating characteristic curve, 0.93 and 0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5 of 17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC peptide–induced T-cell memory responses remained in 13 of 17 study participants (76%) >180 days after infection (P = .01 for comparison with NC-IgG; McNemar test). After 2 vaccine doses, all 18 donors exhibited S1-specific T-cell memory. Conclusions Cytokine release assays for the monitoring of T-cell memory in whole blood may be useful for evaluating complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T-cell immunity. Clinical Trials Registration EudraCT 2021-000349-42.

Type 1 conventional dendritic cells (cDC1) efficiently cross-present antigens that prime cytotoxic CD8

This study analyzed whole blood samples ( n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2–derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (T H ) cells followed by an equally synchronous and durable T H 1-like reactivity reflecting long-lasting T cell memory.

This paper investigates the economic consequences of a haulage company replacing its line-haul diesel trucks with battery-electric ones. It also examines how large truck batteries should be, whether the haulage companies should use public fast chargers to complement their own, and whether public fast chargers have the potential to be profitable. The potential extra cost of losing payload capacity is estimated and there is an investigation of whether a charge-point operator should meet the peak demand for charging. The case under analysis is designed to represent a typical line-haul service between terminals in a major logistics system, with the finding that, in this case, a transition to battery-electric trucks seems cost effective for the company. Moreover, it is advisable for the company to use public fast chargers and these will likely become profitable given that the utilisation factor of the investigated public fast chargers may realistically exceed 20%.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti–RBD-S1 IgG) and for SARS-CoV-2–specific T-cell immunity, reflected by induction of T-cell–derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlap S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher’s exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher’s exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (

Cross-sectional.To describe quality of life in males and females with idiopathic scoliosis.Idiopathic scoliosis is a three-dimensional deformity affecting the growing spine. The prevalence of larger curves, requiring treatment, is higher in females.This cross-sectional study comprised 1519 individuals with idiopathic scoliosis (211 males) with a mean (SD) age of 35.3 (14.9) years. They all answered the Scoliosis Research Society 22 revised (SRS-22r) questionnaire and EuroQol 5-dimension-index (EQ-5D). Five hundred twenty eight were surgically treated (78 males), 535 were brace treated (50 males), and 456 were untreated (83 males). The SRS-22r subscore (excluding the satisfaction domain), the SRS-22r domains and the EQ-5D index score were calculated. Subgroup analyses based on treatment and age were performed. Statistical comparisons were performed using analysis of covariance with adjustments for age and treatment. A P-value less than 0.05 was considered as statistical significant.The mean (SD) SRS-22r subscore was 4.19 (0.61) in males and 4.05 (0.61) in females (P = 0.010). The males had higher scores on the SRS-22r domains function (4.56 vs. 4.42), pain (4.20 vs. 4.00), and mental health (4.14 vs. 3.92) (all P 0.05). The mean (SD) EQ-5D index score was 0.85 (0.22) for males and 0.81 (0.21) for females (P = 0.10). There were minor differences when comparing males and females in treatment and age groups, but both treated and untreated groups had reduced quality of life compared with the national norms.When compared with females, males with idiopathic scoliosis tend to have slightly higher scores in the scoliosis specific SRS-22r but not in the generic quality of life measurement EQ-5D. Quality of life is overall similar between males and females in treatment and age groups, but reduced in comparison with the general population.3.

Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination.SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-γ (IFN-γ) in blood cells stimulatedT-cell reactivity against S1 was reduced in patients with cirrhosis after the 1Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures.EudraCT 2021-000349-42.T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients.

Background Relapse of acute myeloid leukemia (AML) may arise from residual chemoresistant leukemic cells. A hypoxic tumor microenvironment, such as the bone marrow, is known to enhance chemoresistance in various forms of cancer, including AML. Hypoxia inducible factor 1 alpha (HIF-1α) is an important mediator of cellular adaptation to hypoxia. HIF-1α is a constitutively expressed transcription factor that is rapidly degraded under normoxic conditions after hydroxylation by oxygen sensors, such as the HIF prolyl hydroxylases (PHDs). However, under hypoxic conditions the oxygen sensors lose the ability to induce the degradation of HIF-1α resulting in its stabilization and translocation to the nucleolus where it induces the transcription of genes associated with glucose metabolism, angiogenesis, and cell survival. This may result in proliferation of malignant cells, impaired tumor cell differentiation and chemoresistance. Reactive oxygen species (ROS) have been shown to inhibit PHDs and may thereby stabilize HIF-1α, and may thus contribute to chemoresistance. AML cells may generate ROS via the myeloid NADPH oxidase NOX2. We therefore hypothesized that NOX inhibitors would decrease chemoresistance in a hypoxic environment. Materials and Methods The wild type (WT) AML cell line PLB-985 and its NOX2 knocked out (KO) counterpart were cultured for five days in hypoxia (1% oxygen) or normoxia (21% oxygen) in the presence or absence of the NOX inhibitors histamine dihydrochloride (HDC), diphenyleneiodonium (DPI) and GSK2795039. Thereafter cells were exposed to the chemotherapeutic agent daunorubicin for 48 hours (in hypoxia or normoxia) and cell death was determined using the XTT assay. Stabilization of HIF-1α was measured either by western blot or flow cytometry. Differentiation of cells was quantified by measuring the expression of CD14 and CD11b by flow cytometry. Results Hypoxia reduced the sensitivity of WT PLB-985 cells to daunorubicin induced cell death (P 0.5, n=4). Furthermore, NOX2 KO AML cells displayed increased sensitivity to daunorubicin induced killing compared with PLB WT cells in a hypoxic environment (P Conclusions Genetic deletion or pharmacological inhibition of NOX2 sensitized AML cells to daunorubicin induced killing in hypoxic environments. NOX2 may thus be a target for overcoming chemoresistance in AML cells in the hypoxic bone marrow environment. Support This work was supported by Assar Gabrielsson’s Foundation( FB19-64) and other grants used by the research group. Disclosure Information S. Paul: None. H. Grauers Wiktorin: E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Patent. R. Kiffin: None. K. Hellstrand: E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Patent. A. Martner: E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Patent.

Hybrid dual clutch transmissions can reduce fuel consumption and CO 2 emissions significantly at a low cost, but they will lead to torque interrupt shifts in electric vehicle mode. To improve the shift quality, the shift time should be minimized and the impacts between the sleeve teeth and the idler gear dog teeth after speed synchronization should also be minimized. Besides creating noise, these impacts are also responsible for delaying the completion of shift and contribute to wear in the dog teeth. This paper presents a time optimal control strategy for mechanical synchronizers in a hybrid dual clutch transmission, which includes constraints such that impacts between sleeve and gear dog teeth are minimized. It is demonstrated how a mechanical synchronizer can be modeled as a double integrator system and how the standard time-optimal control solution of double integrator system must be modified such that it can be applied to mechanical synchronizers. The result is a feedback control strategy that guarantees minimum speed synchronization time and minimum noise/wear in transmission. The performance of the controller is verified by simulation.

Antallet af mennesker, der lever med multisygdom, er gennem de seneste år steget markant, både som et resultat af en aldrende befolkning, men også på grund af en forbedret medicinsk behandling af, og tertiær forebyggelse hos, mennesker med kroniske sygdomme. Interessen i forskning om multisygdom har også været støt stigende de seneste år, men, trods denne interesse, er der fortsat ingen konsensus om, hvordan multisygdom skal defineres, og varia- tionen i, hvordan multisygdom bliver defineret og brugt i den videnskabelige litteratur, er stor. Med denne artikel vil vi diskutere konsekvenserne af heterogeniteten i definitionen af multisygdom. Vi tager udgangspunkt i en systematisk gennemgang af definitionen af mul- tisygdom, og diskuterer, om begrebet multisygdom giver mening og for hvem, og om vi med de eksisterende definitioner kan risikere at fokusere på andre patienter end dem, der har det største behov. Dette leder derefter over i en diskussion om, hvorvidt definitionsproblematikkerne skaber risiko for, at multisygdom i sig selv som begreb kan føre til overdiagnostik og dermed være til mere skade end gavn for patienterne.

Supplemental Material, sj-docx-1-cob-10.1177_2235042X20981185 for The association between clusters of chronic conditions and psychological well-being in younger and older people—A cross-sectional, population-based study from the Lolland-Falster Health Study, Denmark by Lars Hermann Tang, Lau Caspar Thygesen, Tora Grauers Willadsen, Randi Jepsen, Karen la Cour, Anne Frølich, Anne Møller, Lars Bo Jørgensen and Søren T Skou in Journal of Comorbidity

Myeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i.e. EL-4 lymphoma, MC-38 colorectal carcinoma, and 4T1 mammary carcinoma. In vivo treatment with HDC delayed EL-4 and 4T1 tumor growth and reduced the ROS formation by intratumoral MDSCs. HDC treatment of EL-4 bearing mice also reduced the accumulation of intratumoral MDSCs and reduced MDSC-induced suppression of T cells ex vivo. Experiments using GR1-depleted and Nox2 knock out mice supported that the anti-tumor efficacy of HDC required presence of NOX2+ GR1+ cells in vivo. In addition, treatment with HDC enhanced the anti-tumor efficacy of programmed cell death receptor 1 (PD-1) and PD-1 ligand checkpoint blockade in EL-4- and MC-38-bearing mice. Immunomodulatory effects of a HDC-containing regimen on MDSCs were further analyzed in a phase IV trial (Re:Mission Trial, ClinicalTrials.gov; NCT01347996) where patients with acute myeloid leukemia received HDC in conjunction with low-dose IL-2 (HDC/IL-2) for relapse prevention. Peripheral CD14+HLA-DR−/low MDSCs (M-MDSCs) were reduced during cycles of HDC/IL-2 therapy and a pronounced reduction of M-MDSCs during HDC/IL-2 treatment heralded favorable clinical outcome. We propose that anti-tumor properties of HDC may comprise the targeting of MDSCs. Electronic supplementary material The online version of this article (10.1007/s00262-018-2253-6) contains supplementary material, which is available to authorized users.

The number of people living with multimorbidity has increased dramatically during the last decades, which is associated with harms and costs for individuals as well as societies. This increase is explained by population longevity, but also by better medical treatment and tertiary prevention among patients with chronic diseases. However, the increased prevalence of multimorbidity may owe to the inconsistency of the definition of multimorbidity, which leaves room for both under- and overdiagnosis. The consequences of this overdiagnosis will plausibly have influence on the handling and daily clinical practice regarding the growing number of patients categorized as multimorbid. The theoretical background and hypotheses for the risks of overdiagnosis within multimorbidity concerns a lot of different aspects. Some of the aspects comprise different possibilities for overdiagnosis of diseases. Moreover, some of these diseases have different prognoses and have different meanings, values and treatment preferences for patients. Therefore, it could be relevant in a patient-centred approach for clinicians to conduct a diagnostic review and in dialogue with the patients find out which diagnoses are of importance and which could de-diagnosed. In this workshop we will invite participants to attend the discussion about drivers of overdiagnosis in relation to multimorbidity, and how we can study these problems scientifically. Furthermore, the aim of the workshop is to discuss whether a too broad definition of multimorbidity may result in more harm than benefit for the patients. Finally, we will discuss if diagnostic review in a primary health care setting is a relevant and appropriate approach among patients with multimorbidity who have been overdiagnosed with one or more diseases.

STUDY DESIGN Cross-sectional. OBJECTIVE The aim of this study was to describe the self-experienced trunk appearance in individuals with and without idiopathic scoliosis. SUMMARY OF BACKGROUND DATA Idiopathic scoliosis is the most common spinal deformity. A large scoliotic deformity increases the risk of back pain and pulmonary dysfunction. The deformity has also a psychological impact. METHODS The pictorial part of the spinal appearance questionnaire (pSAQ) was administered to 1416 individuals with idiopathic scoliosis (386 untreated, 529 brace treated, 501 surgically treated) and 272 individuals without scoliosis from the general population. Comparisons were made between individuals with and without scoliosis, between treatment groups and sex in the scoliosis group. RESULTS Mean (95% confidence interval) age of the individuals with scoliosis was 36.2 (35.5-36.9) years and for the individuals without scoliosis 40.2 (37.9-42.4). pSAQ total was 12.3 (12.1-12.5) for individuals with scoliosis and 7.4 (7.3-7.6) for individuals without scoliosis (P

Background Health-related quality of life in adults with idiopathic scoliosis diagnosed before maturity has been reported to be similar between brace-treated and surgically treated individuals. The aim of this study was to compare health-related quality of life in untreated, brace-treated, and surgically treated adults with idiopathic scoliosis diagnosed before skeletal maturity. Subgroup analyses were performed on the basis of age at the time of the study, age of onset, surgical characteristics, and curve magnitude. Methods We included 1,187 adults with juvenile or adolescent idiopathic scoliosis with a mean age (and standard deviation) of 38.8 ±12.7 years. Of these, 347 were untreated, 459 had been brace-treated, and 381 had been surgically treated. The Scoliosis Research Society-22r (SRS-22r) and EuroQol 5-Dimensions (EQ-5D) were used. Statistical analyses were performed using analysis of covariance. Results The mean SRS-22r subscore was 4.15 ± 0.59 points for the untreated group, 4.10 ± 0.57 points for the previously braced group, and 4.01 ± 0.64 points for the surgically treated group (p = 0.007 adjusted for age and sex). The EQ-5D index was 0.82 ± 0.20 for the untreated group, 0.82 ± 0.20 for the previously brace-treated group, and 0.79 ± 0.24 for the surgically treated group (p = 0.026, adjusted for age and sex). Brace cessation was at the mean age of 16.2 ± 1.5 years, and the surgical procedure had been performed at the mean age of 15.3 ± 2.1 years. A more caudal fusion was associated with a lower SRS-22r subscore and EQ-5D index. No differences were observed when comparing individuals with juvenile or adolescent onset scoliosis (all p > 0.05). Conclusions Untreated adults with idiopathic scoliosis had similar health-related quality of life to previously brace-treated individuals, and they had marginally higher health-related quality of life compared with surgically treated individuals. Therefore, both surgical and brace treatments for idiopathic scoliosis could be considered successful from a health-related quality-of-life point of view in adulthood. The age of onset of idiopathic scoliosis does not seem to influence quality of life in adulthood. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

This study investigates the impact of different levels of modeling details on the problem of optimizing the total cost of ownership of a fuel-cell hybrid electric vehicle. In this optimization, the objective function is a weighted sum of operational and component costs over a driving cycle. The former includes the consumed hydrogen and electrical energy, and the latter includes the sum of the battery, fuel-cell, and electric-motor costs. Three methods with different levels of modelling details are investigated; in the first method, the power split between the two power sources together with component sizes are optimized, while assuming nonlinear loss functions for the components. In the second method, the efficiencies of the components are approximated by constant values. In the third method, the problem is simplified further by considering the energy split between the battery and the fuel-cell. As shown in the results, a more detailed model gives more accurate results at the price of increased computation time. However, the simplified models can give similar results as the detailed model in most cases. In some problems though, the model simplifications lead to results that differ notably from those obtained by using the detailed model.

In this paper, the problem of optimal sizing of a series PHEV is studied by formulating a convex program that minimizes the sum of operational and component costs. The solution gives the optimal sizes of the main powertrain components, simultaneously with the vehicle’s optimal energy management. Investigations are performed on driving cycles generated stochastically from real data using Markov chains, with different driving distance distributions and charging patterns. The results show that the optimal component sizing is affected more from the driving distances between charging opportunities, than the speed profile of the driving. With anticipated future battery and petroleum prices, larger battery sizes are obtained.

Study design Cross-sectional. Objective To describe physical activity level and fracture rates in adults with idiopathic scoliosis, diagnosed before maturity, and to compare with a control group. Summary of background data A previous study found a lower level of sporting activities in adults treated for idiopathic scoliosis compared with controls. Other studies have shown a lower bone mass in adults with idiopathic scoliosis compared with controls. Methods One thousand two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and 214 controls (aged 18-70 yr) were included and answered the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about previous fractures. The three scoliosis treatment groups (untreated n = 360, brace n = 460, and surgically treated n = 458) were compared. Furthermore, a comparison based on onset (juvenile n = 169 or adolescent n = 976) was performed. Achieved weekly moderate activity level and metabolic equivalent task (MET) minutes/week were assessed for patients and controls. Statistical comparisons were made with analysis of covariance with adjustments for age, body mass index, and sex. Results The proportion achieving weekly moderate activity level was 962 out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214 (73%) for controls (P = 0.40). The scoliosis patients reported 2016 MET-minutes/week (median value) and the controls 2456 (P = 0.06). Fracture rates did not differ (P = 0.72). Fewer surgically treated individuals achieved moderate activity level (P = 0.046) compared with the untreated and the previously braced individuals. No difference was seen regarding MET-minutes/week (P = 0.86). No differences were seen between individuals with a juvenile onset compared with individuals with an adolescent onset (all P ≥ 0.05). Conclusion Adults with idiopathic scoliosis have similar physical activity level and do not sustain more fractures compared with controls. Adults with surgically treated idiopathic scoliosis have slightly lower physical activity level than previously braced and untreated patients. Onset of idiopathic scoliosis does not affect physical activity level. Level of evidence 2.

The Scoliosis Research Society (SRS) 22r questionnaire is a widely used instrument. To estimate the disorder´s impact on quality of life and to gain knowledge about treatment effects, normative values are needed. Individuals were randomly invited from the general population. 272 individuals (145 females) answered the SRS-22r and EuroQol 5-dimensions (EQ-5D) questionnaires and stratified according to sex and age; ≤19 years (n = 61), 20–39 years (n = 66), 40–59 years (n = 84) and ≥60 years (n = 61). The correlation between SRS-22r and EQ-5D were analyzed. There were modest variations in mean SRS-22r scores (ranging between 4.3 and 4.7). EQ-5D followed the same pattern. The correlation between the SRS-22r was 0.62 (p = 0.001) and 0.61 (p

This paper presents a model based control strategy aimed to reduce noise and wear during gearshifts in conventional and hybrid Dual Clutch Transmissions (DCT and DCTH) and Automated Manual Transmissions (AMT). The control strategy is based on a newly developed dog teeth position sensor layout at China Euro Vehicle Technology AB (CEVT), a detailed simulation model for gear engagement and already existing speed sensors in the transmission. The details of dog teeth position sensor and simulation model are also presented in this paper. During gear shifting, noise is generated because of impacts between the sleeve teeth and the idler gear dog teeth after speed synchronization. Besides noise, these impacts are also responsible for delaying the completion of shift and contribute to wear in the dog teeth, hence reducing the lifespan of the transmission. The simulation model for gear engagement can simulate these impacts. Based on the simulation model and optimal control theory, an ideal dog teeth position trajectory is formulated that avoids the impact between sleeve and idler gear dog teeth, before the start of torque ramp up. The open loop strategy then controls the synchronization torque in the beginning of speed synchronization in such a way that the dog teeth position during shift follows the ideal dog teeth position trajectory. Since the control strategy is based on optimal control theory, its effect on speed synchronization time is minimal. The control strategy is designed in such a way that it can easily be applied in the existing transmission control software. By applying the control strategy on the simulation model, it is shown that the impacts during gear engagement are reduced.

Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23×10−13; odds ratio = 1.36, 95% confidence interval = 1.25−1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.

Thermally expandable microspheres are extensively used in industry as a lightweight filler for many products. The spheres can expand up to 60 times the initial size and are used for different purposes, including material reduction and surface modification. In fused filament fabrication (FFF), a material is deposited in a layer-by-layer process. Typically, FFF objects need not be solid because such objects are typically used for applications with low mechanical stress. Low material infill percentages are commonly used inside a solid outer shell to reduce material usage, weight, and manufacturing time. This paper proposes a new composite filament for FFF consisting of polylactic acid (PLA) and thermally expandable Expancel microspheres in the form of masterbatch granules. These filaments contain unexpanded microspheres that can be expanded during printing by heating. Two types of filaments containing 2 wt% and 5 wt% of masterbatch granules were manufactured and tested. The filaments were successfully used with a commercial 3D printer to manufacture objects with a density of 45% compared to objects manufactured using standard PLA. The tensile strength of these objects changed linearly with density and was comparable to that of PLA objects of the same density prepared using infill patterns. The composite filaments are advantageous in that they can reduce the amount of material used, as is currently done by using different amounts of infill in a pattern. Further, by varying the nozzle temperature, their density can be adjusted directly during printing as well as during fabrication to produce layers of different densities in the same object.

Objective is to explore how multimorbidity is defined in the scientific literature, with a focus on the roles of diseases, risk factors, and symptoms in the definitions.DESIGN: Systematic review.METHODS: MEDLINE (PubMed), Embase, and The Cochrane Library were searched for relevant publications up until October 2013. One author extracted the information. Ambiguities were resolved, and consensus reached with one co-author. Outcome measures were: cut-off point for the number of conditions included in the definitions of multimorbidity; setting; data sources; number, kind, duration, and severity of diagnoses, risk factors, and symptoms. We reviewed 163 articles. In 61 articles (37%), the cut-off point for multimorbidity was two or more conditions (diseases, risk factors, or symptoms). The most frequently used setting was the general population (68 articles, 42%), and primary care (41 articles, 25%). Sources of data were primarily self-reports (56 articles, 42%). Out of the 163 articles selected, 115 had individually constructed multimorbidity definitions, and in these articles diseases occurred in all definitions, with diabetes as the most frequent. Risk factors occurred in 98 (85%) and symptoms in 71 (62%) of the definitions. The severity of conditions was used in 26 (23%) of the definitions, but in different ways. The definition of multimorbidity is heterogeneous and risk factors are more often included than symptoms. The severity of conditions is seldom included. Since the number of people living with multimorbidity is increasing there is a need to develop a concept of multimorbidity that is more useful in daily clinical work. Key points The increasing number of multimorbidity patients challenges the healthcare system. The concept of multimorbidity needs further discussion in order to be implemented in daily clinical practice. Many definitions of multimorbidity exist and most often a cut-off point of two or more is applied to a range of 4-147 different conditions. Diseases are included in all definitions of multimorbidity. Risk factors are often included in existing definitions, whereas symptoms and the severity of the conditions are less frequently included.

Fuel saving potential of hybrid electric vehicles (HEVs) depends mainly on driving cycle and on sizing of powertrain components. Since a complete driving cycle, representing whole life usage a vehicle, is very long it is time consuming to predict the fuel saving potential, especially if many different types of HEV's should be analyzed. This paper presents an energy based method to quickly screen different types of HEVs for many and long driving cycles, in order to find interesting candidates for deeper and more accurate analysis. The technique used also allows to derive the fuel consumption analytically, and thus it is a very effective tool to explain the main fuel savings mechanisms of different types of HEVs and how they are influenced by the driving cycle. Some of the simplifications will lead to errors, but since the sign of the main errors are known it is still easy to draw several clear conclusions using the method. (C) 2016, FAG (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved.

The definition of multimorbidity has been discussed for several years, and research in this field is challenged by various definitions of multimorbidity. Inclusion of risk factors in the definition alongside more severe diseases is widely used, however, questioning the meaning of the concept of multimorbidity. Even though, both symptoms and severity are sometimes included in the broad definitions, the inclusion of risk factors could lead to overdiagnosis. Multimorbidity is rising, and there is a need to address the help to those most in need, but many of the current definitions increase the risk of targeting the wrong patients. Furthermore, diagnoses, including the diagnosis of multimorbidity, can have both positive and negative implications for a single patient. Some patients find identity in a diagnosis whereas others suffer from psychosocial side-effects of diagnoses. In this seminar, we will introduce you to different definitions of multimorbidity and risk of overdiagnosis in this field, and furthermore we will debate the positive and negative implications of diagnoses. Finally, we will invite you to a discussion about consequences of overdiagnosis working with multimorbidity in relation to patients, society, and future research. Objectives To debate the risk of overdiagnosis when working with the concept of multimorbidity clinically and in research. Method Seminar. Based on a systematic review of the definition of multimorbidity and qualitative work among patients with multimorbidity.

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10−20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10−18 (odds ratio = 1.19, 95% confidence interval = 1.14–1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

MM-DCGP_Supplementary_eTable_1_and_2 for The development of multimorbidity during 16 years after diagnosis of type 2 diabetes by Sandra Pouplier, Maria Åhlander Olsen, Tora Grauers Willadsen, Håkon Sandholdt, Volkert Siersma, Christen Lykkegaard Andersen, and Niels de Fine Olivarius in Journal of Comorbidity

Disc-related sciatica has a prevalence of about 2% in adults, but is rare in adolescents. If conservative treatment is unsuccessful, surgery is an option.The aim of this study was to compare the outcomes of surgery for lumbar disc herniation in adolescents with adults in the Swedish Spine Register.This is a prospective observational study: National Quality Register.This study included 151 patients, 18 years or younger, 4,386 patients, 19-39 years, and 6,078 patients, 40 years or older, followed for 1-2 years after surgery.The primary outcomes were patient satisfaction and global assessment of leg and back pain. Secondary outcomes were Visual Analog Scale (VAS) leg pain, VAS back pain, Oswestry disability index (ODI), and EuroQol-5 dimensions (EQ-5D).Statistical analyses were performed with the Welch F test, the chi-square test, and the Wilcoxon signed-rank test.At follow-up, 86% of the adolescents were satisfied compared with 78% in the younger adults and 76% in the older adults group (p.001). According to the global assessment, significantly decreased leg pain was experienced by 87% of the adolescents, 78% of the younger adults, and 71% of the older adults (p.001). Corresponding figures for back pain were 88%, 73%, and 70%, respectively (p.001). All groups experienced significant postoperative improvement of VAS leg pain, VAS back pain, ODI, and EQ-5D (all p.001).The adolescent age group was more satisfied with the treatment than the adult groups. There was a significant improvement in all age groups after surgery.

Objective. To explore views and attitudes among general practitioners (GPs) and researchers in the field of general practice towards problems and challenges related to treatment of patients with multimorbidity. Setting. A workshop entitled Patients with multimorbidity in general practice held during the Nordic Congress of General Practice in Tampere, Finland, 2013. Subjects. A total of 180 GPs and researchers. Design. Data for this summary report originate from audio-recorded, transcribed verbatim plenary discussions as well as 76 short questionnaires answered by attendees during the workshop. The data were analysed using framework analysis. Results. (i) Complex care pathways and clinical guidelines developed for single diseases were identified as very challenging when handling patients with multimorbidity; (ii) insufficient cooperation between the professionals involved in the care of multimorbid patients underlined the GPs’ impression of a fragmented health care system; (iii) GPs found it challenging to establish a good dialogue and prioritize problems with patients within the timeframe of a normal consultation; (iv) the future role of the GP was discussed in relation to diminishing health inequality, and current payment systems were criticized for not matching the treatment patterns of patients with multimorbidity. Conclusion. The participants supported the development of a future research strategy to improve the treatment of patients with multimorbidity. Four main areas were identified, which need to be investigated further to improve care for this steadily growing patient group. OBJECTIVE: To explore views and attitudes among general practitioners (GPs) and researchers in the field of general practice towards problems and challenges related to treatment of patients with multimorbidity.SETTING: A workshop entitled Patients with multimorbidity in general practice held during the Nordic Congress of General Practice in Tampere, Finland, 2013.SUBJECTS: A total of 180 GPs and researchers.DESIGN: Data for this summary report originate from audio-recorded, transcribed verbatim plenary discussions as well as 76 short questionnaires answered by attendees during the workshop. The data were analysed using framework analysis.RESULTS: (i) Complex care pathways and clinical guidelines developed for single diseases were identified as very challenging when handling patients with multimorbidity; (ii) insufficient cooperation between the professionals involved in the care of multimorbid patients underlined the GPs' impression of a fragmented health care system; (iii) GPs found it challenging to establish a good dialogue and prioritize problems with patients within the timeframe of a normal consultation; (iv) the future role of the GP was discussed in relation to diminishing health inequality, and current payment systems were criticized for not matching the treatment patterns of patients with multimorbidity.CONCLUSION: The participants supported the development of a future research strategy to improve the treatment of patients with multimorbidity. Four main areas were identified, which need to be investigated further to improve care for this steadily growing patient group.

BACKGROUND: Many register studies make use of information about permanent nursing home residents. Statistics Denmark (StatD) identifies nursing home residents by two different indirect methods, one based on reports from the municipalities regarding home care in taken place in a nursing home, and the other based on an algorithm created by StatD. The aim of the present study was to validate StatD's nursing home register using dedicated administrative municipality records on individual nursing home residents as gold standard.METHODS: In total, ten Danish municipalities were selected. Within each Danish Region, we randomly selected one municipality reporting to Stat D (Method 1) and one not reporting where instead an algorithm created by StatD was used to discover nursing home residents (Method 2). Method 1 means that municipalities reported to Stat D whether home care has taken place in a nursing home or in a private home. Method 2 is based on an algorithm created by Stat D for the municipalities where Method 1 is not applicable. Our gold standard was the information from the local administrative system in all ten selected municipalities. Each municipality provided a list with all individuals > 65 years living in a nursing home on January 1st, 2013 as well as the central personal number. This was compared to the list of individuals >65 living in nursing home facilities in the same ten municipalities on January 1st, 2013 retrieved from StatD.RESULTS: According to the data received directly from the municipalities, which was used as our gold Standard 3821 individuals were identified as nursing home residents. The StatD register identified 6,141 individuals as residents. Additionally, 556 of the individuals identified by the municipalities were not identified in the StatD register. Overall sensitivity for the ten municipalities in the StatD nursing home register was 0.85 (95% CI 0.84-0.87) and the PPV was 0.53 (95% CI 0.52-0.54). The municipalities for which nursing home status was based on the StatD algorithm (method 2) had a sensitivity of 0.84 (95% CI 0.82-0.86) and PPV of 0.48 (95% CI 0.46-0.50). Both slightly lower than the reporting municipalities (method 1) where the sensitivity was 0.87(95% CI 0.85-0.88) and the PPV was 0.57 (95% CI 0.56-0.59). Additionally, the sensitivity and PPV of the Stat D register varied heavily among the ten municipalities from 0.51 (95% CI 0.43-0.59) to 0.96 (95% CI 0.95-0.98) and PPV correspondingly, from 0.14 (95% CI: 0.11-0.17) to 0.73 (95% CI 0.69-0.77).CONCLUSIONS: The overall PPV of StatD nursing home register was low and differences between municipalities existed. Even in countries with extensive nation-wide registers, validating studies should be conducted for outcomes based on these registers.

To develop reliable and physically based models for the crash behaviour of composite laminates, a thorough understanding of the failure mechanisms is crucial. Compression tests of corrugated Non-Crimp Fabric (NCF) laminates, made of carbon fibre unidirectional (UD) fabric with a [0/90](3S) stacking sequence and epoxy, have been performed to study the energy absorbing damage mechanisms. Samples from the specimens have been studied with optical microscopy and Scanning Electron Microscopy (SEM) to identify the mechanisms involved in the crushing process. The specimens tested fail partly in bending and partly in pure compression with a mode I delamination separating these two regions. In the region failing in pure compression, the main damage mechanisms are kink band formation and matrix cracking of transverse bundles, whereas in the part failing in bending mixed mode delaminations, intralaminar shear fracture of axial bundles and kink band formation through parts of bundles are identified.

This paper proposes a time-efficient method for sub-optimal design of a plug-in hybrid electric vehicle with a parallel powertrain topology. The method finds the optimal design of the vehicle by iteratively using dynamic programming (DP) and convex optimization to minimize sum of operational and component costs over a given driving cycle. In particular, DP is used to optimize energy management, gear shifting and engine on-off for given component sizes, and convex optimization is used to optimize energy management and component sizes using the gear shifting and engine on-off strategies obtained by DP. Next, DP is re-optimized with the component sizes obtained by convex optimization, and the procedure is repeated until the component sizes converge. The result of this iterative method is compared by using DP on a grid of possible component sizes. It is shown that the iterative method gives a result very close to the global optimum in a comparably short time.

This paper introduces a novel method for the simultaneous optimization of energy management and powertrain component sizing of a parallel plug-in hybrid electric vehicle (PHEV). The problem is formulated as a convex optimization problem to minimize an objective function, which is a weighted sum of operational and component costs. The operational cost includes the consumed fossil fuel and electrical energy, whereas the component cost includes the cost of the battery, electric motor (EM), and internal combustion engine (ICE). The powertrain model includes quadratic losses for the powertrain components. Moreover, the combustion engine and the electric motor losses are assumed to linearly scale with respect to the size and the losses of baseline components. The result of the optimization is the variables of the global optimal energy management for every time instant and optimal component sizes. Due to the dependency of the result on the driving cycle, a long real-life cycle with its charging times is chosen to represent a general driving pattern. The method allows the study of the effect of some performance requirements, i.e., acceleration, top speed, and all-electric range, on the component sizes and total cost.

In the past decade, it has been demonstrated that Plug-in Hybrid Electric Vehicles (PHEVs) can significantly reduce petroleum consumptions. However, the extend to which these vehicles can reduce the petroleum consumption highly depends on components size and driving patterns. In other words, PHEVs show the best benefits if the components are dimensioned to match the driver’s driving behavior. In this paper, the effect of different driving patterns on the optimal sizing of three major components of series PHEVs, i.e., battery, electric motor, and engine generator unit is studied. Different driving cycles are generated stochastically from real driving data using Markov chains, to represent life-time driving patterns of different drivers. To find the optimal size of the components, the problem is formulated as a convex optimization problem. The optimization variables (the variables of component size and energy management) are obtained by minimizing a cost function which is the sum of the operational and component costs.

0 0 1 300 1716 University of Gothenburg 14 4 2012 14.0 Normal 0 false false false SV JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0cm; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-ansi-language:SV;} Mutations leading to Ras gene activation are important contributors to myeloid leukemogenesis. Kras is one of three homologues of the Ras family, and oncogenic Kras is frequently found in monocytic forms of acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and myeloproliferative diseases (MPD). Earlier studies show that excessive amounts of reactive oxygen species (ROS) are produced in Kras-mutated myeloid malignancies. Myeloid cells, including Kras-mutated leukemic cells, express the ROS-generating enzyme NOX2. Relatively little is known about the impact of ROS formation, in particular NOX2-derived ROS formation, on leukemogenesis. Mice where oncogenic Kras was induced in hematopoietic cells of LSL-KrasG12D and Mx1-Cre double transgenic mice with ensuing myeloproliferation were treated with a histamine H2-receptor selective NOX2 inhibitor, Nα -methyl histamine (NMH) to assess whether NOX2 is a feasible therapeutic target in Kras-driven leukemia. Spleens of diseased Kras mice were infiltrated with mature CD11b+Gr1+ myeloid cells that expressed NOX2 and produced ROS. The NOX2-dependent formation of ROS in CD11b+Gr1+ cells was inhibited by NMH. In vivo administration of NMH delayed the development of myeloproliferative disease and significantly prolonged survival of Kras mice (p=0.003). In contrast, treatment with NMH did not alter the survival of mice when Kras expression was induced in hematopoietic cells of NOX2-deficient mice that did not produce ROS (Nox2-/-, LSL-KrasG12D and Mx1-Cre triple transgenic mice). In Kras-mutated Nox+/+ mice, but not in Kras-mutated Nox-/- mice, the in vivo administration of NMH entailed diminished ROS levels and reduced oxidative stress as reflected by reduced DCFDA and anti-8 Hydroxyguanosine staining. We propose that NOX2-derived ROS in Kras-mutated hematopoetic cells mediate genomic instability that may contribute to the progression of leukemia. Strategies to target NOX2 should be further evaluated in Ras-mutated hematopoietic cancer. Citation Format: Ebru Aydin, Alexander Hallner, Hanna Grauers Wiktorin, Anna Staffas, Kristoffer Hellstrand, Anna Martner. NOX2 inhibition reduces oxidative stress and prolongs survival of mice with Kras induced myeloproliferative disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 441.

The NOX2 enzyme is highly expressed in normal myeloid cells, as well as in subpopulations of malignant myeloid cells, where it contributes to the generation of reactive oxygen species (ROS). We have utilized mice and leukemic cells genetically depleted of NOX2 and the NOX2-specific inhibitor histamine dihydrochloride (HDC) to further elucidate the role of NOX2-derived ROS in hematopoietic cancer. HDC was found to promote the maturation of human DCs from monocytes and to enhance T cell priming. In addition, treatment of mice with HDC reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in Nox2-/- mice. HDC was also found to facilitated the maturation and inhibit the proliferation of NOX2-expressing human acute myeloid leukemia (AML) cells. These effects were absent in NOX2-/- AML cells. In microarray analysis, HDC was found to regulate the expression of genes involved in cell differentiation and cell cycle progression in NOX2+ but not in NOX2-/- AML cells. In a xenograft mouse model, systemic treatment with HDC reduced the expansion of engrafted monocytic AML cells in bone marrow but did not exert anti-leukemic activity against engrafted NOX2-/- AML cells.

Background: Knowledge about prevalent and deadly combinations of multimorbidity is needed. Objective: To determine the nationwide prevalence of multimorbidity and estimate mortality for the most prevalent combinations of one to five diagnosis groups. Furthermore, to assess the excess mortality of the combination of two groups compared to the product of mortality associated with the single groups. Design: A prospective cohort study using Danish registries and including 3.986.209 people aged ≥18 years on 1 January, 2000. Multimorbidity was defined as having diagnoses from at least 2 of 10 diagnosis groups: lung, musculoskeletal, endocrine, mental, cancer, neurological, gastrointestinal, cardiovascular, kidney, and sensory organs. Logistic regression (odds ratios, ORs) and ratio of ORs (ROR) were used to study mortality and excess mortality. Results: Prevalence of multimorbidity was 7.1% in the Danish population. The most prevalent combination was the musculoskeletal–cardiovascular (0.4%), which had double the mortality (OR, 2.03) compared to persons not belonging to any of the diagnosis groups but showed no excess mortality (ROR, 0.97). The neurological–cancer combination had the highest mortality (OR, 6.35), was less prevalent (0.07%), and had no excess mortality (ROR, 0.94). Cardiovascular–lung was moderately prevalent (0.2%), had high mortality (OR, 5.75), and had excess mortality (ROR, 1.18). Endocrine–kidney had high excess mortality (ROR, 1.81) and cancer–mental had low excess mortality (ROR, 0.66). Mortality increased with the number of groups. Conclusions: All combinations had increased mortality risk with some of them having up to a six-fold increased risk. Mortality increased with the number of diagnosis groups. Most combinations did not increase mortality above that expected, that is, were additive rather than synergistic.

The efficiency of immune-mediated clearance of cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase–derived reactive oxygen species. We aimed at defining the effects of histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of these mechanisms for tumor growth. Histamine was found to promote the maturation of human DCs from monocytes by increasing the expression of HLA-DR and costimulatory molecules, which resulted in improved induction of Th cells with Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic cells showed that histamine facilitated myeloid cell maturation only in cells capable of generating reactive oxygen species. Treatment of mice with histamine reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient (gp91phox−/−) mice. We propose that strategies to target the myeloid NADPH oxidase may facilitate the development of endogenous DCs in cancer.

Increasingly intelligent vehicle driving systems are rapidly being developed, and will in the future become a necessity for sustainable, convenient and safe mobility in our ever more urbanized world. This paper presents an innovative approach for the control of a fully electric vehicle approaching a road segment with Multiple Traffic Lights (TL). By utilizing Vehicle to Vehicle (V2V) and Vehicle-to-Infrastructure (V2I) communication, the energy consumption for the maneuver completion can be reduced. The problem is approached from a Model Predictive Control (MPC) framework. The performance of the system is evaluated using a complex simulation toolchain representing the vehicle, powertrain, driver, and road including the traffic conditions. The results have shown an overall energy consumption reduction of 29 % for an idealized case and 17 % for a real road simulated scenario as compared to ‘normal’ human driver behavior.

This work discusses the practical limits imposed by magnetic saturation for the force density in low-speed permanent-magnet electric machines. The force density dependence on current density and slot depth is investigated with the aid of finite-element modeling. For saturation reasons, shallow slots are more favorable for achieving high force densities. However, for thermal reasons, deeper slots become favorable. Therefore, an optimum slot depth that maximizes the force density for each current density level exists. The maximum allowable slot depth range for four low-speed applications has been identified for a given maximum motor diameter.

This paper discusses two of the mechanisms that limit the attainable force density in slotted low-speed permanent-magnet (PM) electric machines. Most of the interest is focused on the force density limits imposed by heating of the windings and by stator reactance. The study is based on analytical models for the force and reactance calculations and a lumped parameter thermal model. It is found that in a machine with an indirectly cooled stator, it is difficult to achieve a force density greater than 100 kN/m/sup 2/ due to temperature limits. A high force density is achieved by using deep slots, which lead to high reactance. The high reactance severely increases the converter kilovolt-ampere requirement and total system cost. It is also shown that the cost caused by the high reactance will also limit the force density reached. In machines with one slot per pole per phase, the reactance limited the useful slot depth to approximately 200 mm. However, in machines having a greater number of slots per pole per phase the reactance becomes no longer an important limiting factor for the slot depth and force density.