All-Microwave Leakage Reduction Units for Quantum Error Correction with Superconducting Transmon Qubits.

Minimizing leakage from computational states is a challenge when using many-level systems like superconducting quantum circuits as qubits. We realize and extend the quantum-hardware-efficient, all-microwave leakage reduction unit (LRU) for transmons in a circuit QED architecture proposed by Battistel et al. This LRU effectively reduces leakage in the second- and third-excited transmon states with up to 99% efficacy in 220 ns, with minimum impact on the qubit subspace. As a first application in the context of quantum error correction, we show how multiple simultaneous LRUs can reduce the error detection rate and suppress leakage buildup within 1% in data and ancilla qubits over 50 cycles of a weight-2 stabilizer measurement.

Self-management behaviour after a physiotherapist guided blended self-management intervention in patients with chronic low back pain: A qualitative study.

BACKGROUND: Self-management support is considered an important component in the physiotherapeutic treatment of people with chronic low back pain. The stratified blended physiotherapy intervention e-Exercise Low Back Pain is an example of a self-management intervention. More insight may contribute to improving blended interventions to stimulate self-management after treatment and thus hopefully prevent chronicity and/or relapses in patients with chronic low back pain. OBJECTIVES: The aim of this study was to gain an in-depth understanding of the self-management behaviour after a physiotherapist guided blended self-management intervention in people with chronic low back pain. DESIGN: A qualitative study with semi-structured interviews nested within a randomized controlled trial on the (cost-)effectiveness of e-Exercise Low Back Pain was conducted. METHOD: Thematic analysis was used to analyse the transcriptions. A hybrid process of both deductive and inductive approaches was used. RESULTS: After 12 interviews, data saturation was reached. Analysis of the data yielded six themes related to self-management behaviour: illness beliefs, coping, cognitions, social support and resource utilization, physiotherapeutic involvement and motivation. CONCLUSIONS: In our study the majority of the participants seemed to show adequate self-management behaviour when experiencing low back pain. Most participants first try to gain control over their low back pain themselves when experiencing a relapse before contacting the physiotherapist. Participants struggle in continuing health behaviour in pain free periods between relapses of low back pain. Physiotherapists are recommended to encourage long-term behaviour change. Additionally, better facilitation by the physiotherapist or additional functionalities in the app to stimulate social support might have a useful contribution.

Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands.

BACKGROUND: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited. OBJECTIVE: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice. METHODS AND MATERIALS: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status. RESULTS: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0-5.2). The median OS after ORC was 5.0 years (95%CI 4.3-5.6) versus 5.8 years after RARC (95%CI 5.1-6.5). The median RFS was 3.8 years (95%CI 3.1-4.5) after ORC versus 5.0 years after RARC (95%CI 3.9-6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84-1.20) and for RFS 1.08 (95%CI 0.91-1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage. CONCLUSION: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC.

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH).

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER: Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE: 31 July 2015. DATE OF FIRST PATIENT'S ENROLMENT: 26 January 2016.

[Euthanasia in patients with dementia]. / Euthanasie bij patiënten met dementie.

BACKGROUND: Euthanasia in patients with dementia is legally permitted, but many physicians experience it as (too) complex. They are frightened of the legal consequences and do not know how to assess the nature of the suffering. They also find it difficult to assess the patient's ability to provide consent. CASE DESCRIPTION: Here we describe two cases of patients who were registered at Euthanasia Expertise Centre by a family member: a 72-year-old woman who had been diagnosed with Alzheimer disease 18 months previously and a 67-year-old man with Lewy body dementia. During the various consultations we had with them we were given a distinct picture of the nature of their suffering, and it became clear to us why they found this suffering unbearable. CONCLUSION: By paying extra attention to the assessment of the ability to give consent and by exploring the degree of suffering experienced it is possible to meet the request for euthanasia by a patient with dementia within the framework of the law.

Are the Dutch long-term care organizations getting better? A trend study of quality indicators between 2007 and 2009 and the patterns of regional influences on performance.

OBJECTIVE: and setting The Dutch long-term care organizations, providing somatic care, psycho-geriatric care and home care, have to measure the quality of care through client-related and professional indicators since 2007. At the same time, competition was introduced with regional stimuli from healthcare insurers. The first aim of this study is to determine the trends of the national performance on client-related and professional quality indicators for the period 2007-09 in long-term care organizations in the Netherlands. The second aim is to determine the influence of the region on the quality performance in 2009. DESIGN AND PARTICIPANTS: We performed trend analyses on the indicators of clients of 2115 long-term care organizations. We used multivariate analyses to determine the difference in national performance between 2007 and 2009 and to calculate the influence of the region on the performance of 2009. INTERVENTION: None. MAIN OUTCOME MEASURES: Client-related and professional indicators. RESULTS: The national performance on client-related indicators for somatic care and home care increased and for psycho-geriatric care the quality performance became worse. The professional indicators for intramural care improved between 2007 and 2009. Region influences the performance. In general, organizations in the west of the Netherlands performed worse than other regions (with exception of home care). CONCLUSIONS: The study suggests that working with quality indicators in long-term care organizations for older people may lead to a better performance on several indicators. The influence of the region on the quality is significant, which could be caused by Dutch healthcare insurers.

Is the myonuclear domain size fixed?

It has been suggested that the number of myonuclei in a muscle fibre changes in proportion to the change in fibre size, resulting in a constant myonuclear domain size, defined as the cytoplasmic volume per myonucleus. The myonuclear domain size varies, however, between fibre types and is inversely related with the oxidative capacity of a fibre. Overall, the observations of an increase in myonuclear domain size during both maturational growth and overload-induced hypertrophy, and the decrease in myonuclear domain size during disuse- and ageing-associated muscle atrophy suggest that the concept of a constant myonuclear domain size needs to be treated cautiously. It also suggests that only when the myonuclear domain size exceeds a certain threshold during growth or overload-induced hypertrophy acquisition of new myonuclei is required for further fibre hypertrophy.

Macrodystrophia lipomatosa: macrodactyly related to affected nerves, and a review of the literature.

Macrodystrophia lipomatosa (ML) is a rare disease causing congenital local gigantism of part of an extremity mostly through proliferation of fibro-adipose tissue. This study is one of few that specifically describe 8 ML patients with histological confirmation of the diagnosis combined with the 79 histologically confirmed cases already described in the literature. The goals of this study are to describe this malformation by using only histologically confirmed cases, to offer some insight on current opinions on ML by reviewing the histologically confirmed cases described in the literature, and to make the postulation of autonomic nerve dysfunction as the aetiology of ML more plausible.

Integrating a MRI scanner with a 6 MV radiotherapy accelerator: impact of the surface orientation on the entrance and exit dose due to the transverse magnetic field.

At the UMC Utrecht, in collaboration with Elekta and Philips Research Hamburg, we are developing a radiotherapy accelerator with integrated MRI functionality. The radiation dose will be delivered in the presence of a lateral 1.5 T field. Although the photon beam is not affected by the magnetic field, the actual dose deposition is done by a cascade of secondary electrons and these electrons are affected by the Lorentz force. The magnetic field causes a reduced build-up distance: because the trajectory of the electrons between collisions is curved, the entrance depth in tissue decreases. Also, at tissue-air interfaces an increased dose occurs due to the so-called electron return effect (ERE): electrons leaving tissue will describe a circular path in air and re-enter the tissue yielding a local dose increase. In this paper the impact of a 1.5 T magnetic field on both the build-up distance and the dose increase due to the ERE will be investigated as a function of the angle between the surface and the incident beam. Monte Carlo simulations demonstrate that in the presence of a 1.5 T magnetic field, the surface dose, the build-up distance and the exit dose depend more heavily on the surface orientation than in the case without magnetic field. This is caused by the asymmetrical pointspread kernel in the presence of 1.5 T and the directional behaviour of the re-entering electrons. Simulations on geometrical phantoms show that ERE dose increase at air cavities can be avoided using opposing beams, also when the air-tissue boundary is not perpendicular to the beam. For the more general case in patient anatomies, more problems may arise. Future work will address the possibilities and limitations of opposing beams in combination with IMRT in a magnetic field.

[An infant with a swelling of the cheek]. / Een pasgeborene met een gezwollen wang.

A 2-weeks-old girl was presented with a swelling of the right parotid gland, due to acute suppurative parotitis caused by Staphylococcus aureus.

Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.

Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in plasma were found, though total sialic acid in plasma was strongly decreased. Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG pattern. Some of the known CDG subtypes were excluded. O-Glycosylation was investigated by isoelectric focusing of apolipoprotein C-III, which showed increased fractions of hyposialylated isoforms. In a consecutive study a defect in the conserved oligomeric Golgi complex was established at the level of subunit COG-7, leading to disruption of multiple glycosylation functions of the Golgi. This report on patients with a new variant of CDG, due to a multiple Golgi defect, emphasizes in addition to sialotransferrins the importance of analysis of a serum O-linked glycoprotein, e.g. apolipoprotein C-III, in unclassified CDG-X cases.

Carnitine-acylcarnitine translocase deficiency: case report and review of the literature.

AIM: Carnitine-acylcarnitine translocase (CACT) deficiency is an inborn error of metabolism involving the mitochondrial beta-oxidation of long-chain fatty acids. The aim of this study was to report on a new case (neonatal phenotype) and review the literature data on 24 previously reported cases. METHODS: Clinical data of the new case are described and compared with the previous reports. RESULTS: The patient with a novel mutation had clinical features and biochemical findings similar to those of the other reported patients. CONCLUSION: CACT is an entity in which clinical encephalopathy, hepatomegaly and arrythmias are common. Hyperammonaemia and elevation of creatine kinase seem to be constant findings as in other disorders of mitochondrial beta-oxidation of long-chain fatty acids. The mortality rate is very high.

[Behçet's disease in a Dutch boy with painful skin lesions]. / De ziekte van Behçet bij een Nederlandse jongen met pijnlijke huidafwijkingen.

A 14-years-old Dutch boy had pain in both calves, recurrent oral ulcers, fever, hoarseness and erythema nodosum-like skin lesions. Laryngoscopic examination revealed a vocal cord ulcer and leukocytoclastic vasculitis was visible in a skin biopsy. Based on the clinical picture, the diagnosis of 'incomplete juvenile Behçet's disease' was established. During treatment with colchicine, genital ulcers developed. These disappeared after local treatment with corticosteroids. Juvenile Behçet's disease is rare in Western Europe and the diagnosis is often difficult. Diagnostic criteria have been formulated, but in most cases there is a delay before these criteria are fulfilled due to the slow clinical course of the disease. All organ systems may be affected; mucocutaneous and skin lesions are the most frequent manifestations. Therapy depends on the severity and the symptoms of the disease.

[Diagnostic image (128). A boy who refused to walk. Spondylodiscitis LIV-LV]. / Diagnose in beeld (128). Een jongetje dat niet meer lopen wil. Spondylodiscitis LIV-LV.

One week after a fall from his buggy, a 2-year-old boy was seen at the first-aid department because he refused to walk. A bone scan and MRI revealed spondylodiscitis at the left side of the discus Liv-Lv and a psoas abscess.

Phenotypic variability of the cat eye syndrome. Case report and review of the literature.

We present a male infant with preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome. The clinical features in our patient show phenotypic overlap with the cat eye syndrome, as illustrated by the review of 105 reported cases. Cytogenetic analysis revealed a supernumerary marker chromosome, which was identified by microdissection and fluorescence in situ hybridization as an isodicentric chromosome 22(pter --> q11.2::q11.2 --> pter). It was proved with probes specific for the cat eye syndrome critical region that this region was present in quadruplicate in the propositus. We conclude that CES is characterized by large phenotypic variability, ranging from near normal to severe malformations, as reflected in the neurodevelopmental outcome. Preauricular skin tags and/or pits are the most consistent features, and suggest the presence of a supernumerary bisatellited marker chromosome 22 derived from duplication of the CES critical region.

[Physician-assisted suicide of a patient suffering from a psycho-organic disorder]. / Hulp bij zelfdoding bij een patiënt met een organisch-psychiatrische stoornis.

A 71-year-old man suffering from vascular dementia since four years asked for physician-assisted suicide. In the Netherlands physician-assisted suicide, which is forbidden by law, remains an intricate dilemma in medical practice. As far as it concerns untreatable terminal patients who decide to put an end to their lives in agreement with and assisted by their physician, procedures are well defined. The present case may be used as an example in the development of a protocol for physician-assisted suicide in patients who are not terminal in the short term, but who suffer unbearably with no prospect of remission. After the protocol securing various formal and medical consequences was run through, the patient was assisted by handling him a high-dose solution of a barbiturate which he drank himself. The procedure incorporates several second and third opinions. First, the chief psychiatrist of the psychiatric hospital assesses the request. Second, a committee consisting of a number of independent professionals form a second opinion. They have no direct responsibility in the treatment of the patient. The patient also may consult an independent consultant psychiatrist with specific knowledge in the domain of his disorder for a third opinion. This procedure was found legally as well as medically sound, and was approved by the public prosecutor after consultation with the Dutch forum of Procurators-General.

Characterization of a de novo unbalanced translocation t(14q18q) using microdissection and fluorescence in situ hybridization.

We report on a patient with a de novo translocation between the long arms of chromosomes 14 and 18. The translocation was studied using microdissection in combination with fluorescence in situ hybridization (micro-FISH). Five copies of the chromosomes involved in the translocation were isolated by microdissection and amplified by means of degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). Reverse chromosome painting with the biotin-labeled PCR product showed that part of the q-arm of chromosome 18 had no signal. The deletion was characterized further by FISH with band-specific probes and it was concluded that the rearrangement was unbalanced: 46,XY,t(14;18)(14pter-->14q22::18q21.1-->18qter) (18pter-->18q12.2::14q22-->14qter). The patient, who presented with psychomotor retardation, mild obesity, pes equinovarus, strabismus, and facial anomalies, is compared with previously reported patients with an interstitial deletion of band 18q12.

Does impaired growth of PKU patients correlate with the strictness of dietary treatment? National Dutch PKU Steering Committee.

To assess whether growth retardation in patients with phenylketonuria (PKU) is related to the strictness of their dietary treatment, the relationship between Z scores for height up to 3 y of age and different indices of dietary control in 103 early treated Dutch PKU patients was studied. As indices of dietary control, the mean phenylalanine (Phe) concentration, the frequency of plasma Phe concentrations < 200 and < 120 micromol/l, and the standard deviation of the individual plasma Phe concentrations were studied. These measures of the dietary control were divided into quartiles. The mean Z score of the studied patients showed a decrease of 0.18/y (SD 0.36). No statistically significant difference between any of the quartiles of the studied indices with growth retardation was found. None of the used indices of dietary control based on plasma Phe concentrations showed a relationship between different degrees of the strictness of dietary treatment with growth retardation in Dutch PKU patients.

Clinical outcome and long-term management of 17 patients with propionic acidaemia.

UNLABELLED: A retrospective study was performed on the clinical outcome and long-term treatment of 17 patients with propionic acidaemia diagnosed during the last 20 years in our hospital. The study group consisted of 12 patients with early onset type of disease and 5 patients with late onset. Seven (41%) patients died, five with early onset and two with late onset. The deceased early onset patients had a median survival of 0.4 years while the deceased late onset patients died at the age of 2.8 and 4 years respectively. Median age of the living early onset patients was 5.2 (1-9.25) years, the late onset patients were 4, 7 and 23 years old. Patients were all treated with natural protein restriction and in most cases carnitine and metronidazole were added. The early onset patients were almost all treated with daily home tube feeding. The mean natural protein intake of early onset patients (6.3 +/- 1.5 g/day) was significantly lower than the natural protein intake of late onset patients (17.6 +/- 5.3 g/day). Supplemental protein intake was higher in early onset patients. The general neurological outcome of our study group was satisfactory with a better outcome for early onset patients. As to growth, many patients showed a failure to thrive, this was particularly for height. The strong protein restriction during the first years of life probably contributed to this. CONCLUSION: The prognosis for patients with propionic acidaemia appeared to be satisfactory in terms of survival and outcome characteristics such as neurological and mental development. Despite these results the authors feel that the prognosis and quality of life of these patients might be improved with liver transplantation or possibly somatic gene therapy in the future.