Bihormonal fully closed-loop system for the treatment of type 1 diabetes: a real-world multicentre, prospective, single-arm trial in the Netherlands.

Background: Management of insulin administration for intake of carbohydrates and physical activity can be burdensome for people with type 1 diabetes on hybrid closed-loop systems. Bihormonal fully closed-loop (FCL) systems could help reduce this burden. In this trial, we assessed the long-term performance and safety of a bihormonal FCL system.

Dual hormone fully closed loop in type 1 diabetes: a randomised trial in the Netherlands - study protocol.

Introduction: The management of type 1 diabetes (T1DM) has undergone significant advancements with the availability of novel technologies, notably continuous and flash glucose monitoring (CGM and FGM, respectively) and hybrid closed loop (HCL) therapy. The dual hormone fully closed loop (DHFCL) approach with insulin and glucagon infusion has shown promising effects in small studies on glycaemic regulation and quality of life in T1DM.

Methods And Analysis: The Dual Hormone Fully Closed Loop for Type 1 Diabetes (DARE) study is a non-commercial 12-month open-label, two-arm randomised parallel-group trial.

Bihormonal Artificial Pancreas With Closed-Loop Glucose Control vs Current Diabetes Care After Total Pancreatectomy: A Randomized Clinical Trial.

Importance: Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking.

Objective: To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy.

Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial.

Objective: To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas (AP) in adults with type 1 diabetes.

Research Design And Methods: In this outpatient, randomized, crossover trial, 2-week fully closed loop glucose control (AP therapy) was compared with 2-week open loop control (patient's normal insulin pump therapy with a glucose sensor if they had one).

Results: A total of 23 patients were included in the analysis.

Acceptance of the Artificial Pancreas: Comparing the Effect of Technology Readiness, Product Characteristics, and Social Influence Between Invited and Self-Selected Respondents.

Background: Psychosocial factors that may affect acceptance of artificial pancreas (AP) systems have been investigated in small sample sizes of highly motivated, self-selected persons with type 1 diabetes (T1DM) with a focus on product characteristics. We aimed to develop a valid survey to investigate the association of technology readiness and social influence with AP acceptance in a larger sample, including both self-selected and invited respondents with T1DM.

Methods: An online survey was developed based on established questionnaires.

Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.

The biological pathways involved in amyotrophic lateral sclerosis (ALS) remain elusive and diagnostic decision-making can be challenging. Gene expression studies are valuable in overcoming such challenges since they can shed light on differentially regulated pathways and may ultimately identify valuable biomarkers. This two-stage transcriptome-wide study, including 397 ALS patients and 645 control subjects, identified 2,943 differentially expressed transcripts predominantly involved in RNA binding and intracellular transport.

A Review of Safety and Design Requirements of the Artificial Pancreas.

As clinical studies with artificial pancreas systems for automated blood glucose control in patients with type 1 diabetes move to unsupervised real-life settings, product development will be a focus of companies over the coming years. Directions or requirements regarding safety in the design of an artificial pancreas are, however, lacking. This review aims to provide an overview and discussion of safety and design requirements of the artificial pancreas.

Performance and safety of an integrated bihormonal artificial pancreas for fully automated glucose control at home.

Aims: To assess the performance and safety of an integrated bihormonal artificial pancreas system consisting of one wearable device and two wireless glucose sensor transmitters during short-term daily use at home.

Methods: Adult patients with type 1 diabetes using an insulin pump were invited to enrol in this randomized crossover study. Treatment with the artificial pancreas started with a day and night in the clinical research centre, followed by 3 days at home.

Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels.

Aims: To evaluate the pharmacokinetics and pharmacodynamics of different doses of glucagon administered subcutaneously (s.c.) at different blood glucose levels.

Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study.

Sporadic amyotrophic lateral sclerosis is a multifactorial disease of environmental and genetic origin. In a previous large multicenter genome wide study, common genetic variation in the Kinesin-Associated Protein 3 (KIFAP3) gene (rs1541160) was reported to have a significant effect on survival in amyotrophic lateral sclerosis patients. However, this could not be replicated in 3 smaller independent cohorts.

[Artificial pancreas for automated glucose control].

Strict glucose control is important for patients with diabetes mellitus in order to prevent complications. However, many patients find it difficult to achieve the recommended HbA1c level. The possibility of hypoglycaemia plays an important role in this.

Increased paternal age and the influence on burden of genomic copy number variation in the general population.

Genomic copy number variations (CNVs) and increased parental age are both associated with the risk to develop a variety of clinical neuropsychiatric disorders such as autism, schizophrenia and bipolar disorder. At the same time, it has been shown that the rate of transmitted de novo single nucleotide mutations is increased with paternal age. To address whether paternal age also affects the burden of structural genomic deletions and duplications, we examined various types of CNV burden in a large population sample from the Netherlands.

Gene expression profile of SOD1-G93A mouse spinal cord, blood and muscle.

The exact pathway leading to neuron death and muscle atrophy in amyotrophic lateral sclerosis (ALS) has not yet been elucidated. Gene expression profile of spinal cord, blood and muscle could provide signalling pathways and systemic alterations useful for future biomarker development. In our study we compared whole genome expression profiles of lumbar spinal cord with peripheral blood and tibialis anterior muscle in 16 mutant SOD1-G93A mice and 15 wild-type littermates.

Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.

Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. Individuals with ALS rapidly progress to paralysis and die from respiratory failure within 3 to 5 years after symptom onset. Epidemiological factors explain only a modest amount of the risk for ALS.

Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered.

NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral sclerosis.

Mutations in NIPA1 cause Hereditary Spastic Paraplegia type 6, a neurodegenerative disease characterized by an (upper) motor neuron phenotype. Deletions of NIPA1 have been associated with a higher susceptibility to amyotrophic lateral sclerosis (ALS). The exact role of genetic variation in NIPA1 in ALS susceptibility and disease course is, however, not known.

SMN1 gene duplications are associated with sporadic ALS.

Objective: To investigate the role of SMN1 and SMN2 copy number variation and point mutations in amyotrophic lateral sclerosis (ALS) pathogenesis in a large population.

Methods: We conducted a genetic association study including 847 patients with ALS and 984 controls. We used multiplexed ligation-dependent probe amplification (MLPA) assays to determine SMN1 and SMN2 copy numbers and examined effects on disease susceptibility and disease course.

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.

Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence.

Copy number variants on the X chromosome in women with primary ovarian insufficiency.

Objective: To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions.

Design: Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome.

Setting: Multicenter genetic cohort study in the Netherlands.

A large genome scan for rare CNVs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations.

Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis.

We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.

Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients.

Background: Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.

Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci.