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Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease.KL1333 aims to normali

Promoting the bioeconomy to aid in the achievement of sustainability goals has increased demand for biomass as feedstock. Residual biomass from agricultural production is an attractive option, as it is a by-product that does not compete with food production. However, crop residues are important for the preservation of soil quality, especially for the maintenance of soil organic carbon. Therefore,

The linear inverse problem associated with the standard model for hyperspectral image recovery from CASSI measurements is considered. This is formulated as the minimization of an objective function which is the sum of a total variation regularizer and a least squares loss function. Standard first-order iterative minimization algorithms, such as ISTA, FISTA and TwIST, require as input the value of

Background: Family members play a crucial role in supporting women with breast cancer during their recovery. In the complex situation of being an informal caregiver, their own health and ability to support the patient needs to be acknowledged. The aim was to explore the experiences, needs and roles of family members throughout the rehabilitation process of women with breast cancer. Methods: A qual

Staging Alzheimer’s disease on the basis of the disease’s biological underpinnings might help with stratification and prognostication, both in the clinical setting and in clinical trials. We propose a staging model based on only five biomarkers, which are related to amyloid-β and tau pathologies in different ways and can be measured with a single sample of cerebrospinal fluid.

PURPOSE The role of consolidation radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) is controversial. METHODS The IELSG37 trial, a randomized noninferiority study, aimed to assess whether irradiation can be omitted in patients with PMBCL with complete metabolic response (CMR) after induction immunochemotherapy. The primary end point was progression-free survival (PFS) at 30

Silica nanofluids are prepared with a concentration varying from 0.001 vol.% to 0.003 vol.%, and pool boiling of the nanofluids is experimentally investigated. It is found that critical heat flux and heat transfer coefficient increase by a maximum of 62.66% and 45.88% compared with deionized water. The best boiling performance is achieved with the nanofluid of 0.002 vol.%. In addition, the paper f

We study the notion of (additive) separability of a function of several variables with respect to a hypergraph (H-graph). We prove the existence of a unique minimal H-graph with respect to which a function is separable and show that the corresponding minimal decomposition of the function can be obtained through a recursive algorithm. We then focus on (strategic form) games and propose a concept of

Anorectal malformations (ARM) are rare congenital anomalies with an overall prevalence of 3.32 per 10,000 pregnancies. ARM describe a spectrum of anomalies of the anus and rectum ranging from a minimally displaced anal canal to a complete fusion of the anorectum, vagina and urethra with hypoplastic sphincter and pelvic floor muscle. Aberrant septation of the hindgut with anomalous cloacal membrane

Background and objective: Clinical practice guidelines for prostate cancer (PCa) are a valuable resource for everyday clinical practice. The clinical practice guidelines and recommendations produced by various societies should demonstrate a considerable level of consistency in terms of quality, regardless of the society that developed these given the common evidence base. However, to date, no stud

One of the most pressing questions we face as biologists is to understand how climate change will affect the evolutionary dynamics of natural populations and how these dynamics will in turn affect population recovery. Increasing evidence shows that sexual selection favors population viability and local adaptation. However, sexual selection can also foster sexual conflict and drive the evolution of

Future connected vehicles will require high-performance communication technologies for advanced cooperative driving applications such as maneuvering and cooperative perception. mmWave communications can meet the bandwidth requirements of such applications, but the typically harsh propagation conditions of vehicular environments hinder the broad adoption of mmWave devices on cars. Reconfigurable in

Party responsiveness to public opinion is a key question in the study ofdemocratic representation. While numerous studies have examined partyresponsiveness on broad ideological dimensions, there is less comparativeresearch on when and how parties respond to public opinion on morespecific issue dimensions. We aim to address this research gap by studyingparty positional responsiveness on seven issue

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998–2017 in Sweden, and 3,900,880 age- and sex-matched controls without d

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on nove

We present a continuous microwave photon counter based on superconducting cavity-coupled semiconductor quantum dots. The device utilizes photon-assisted tunneling in a double quantum dot with tunneling events being probed by a third dot. Our device detects both single and multiple-photon absorption events independently, thanks to the energy tunability of a two-level double-dot absorber. We show th

Background: Elevated filling pressure is a hallmark of heart failure (HF) and portends poor prognosis. Accurate diagnosis is challenging, given that patients with normal filling pressure at rest develop disproportionate elevation with sudden preload increase. We aimed to test the accuracy of the ratio between mitral inflow velocity (E) and left ventricular stroke volume (SV) to identify patients w

In recent years, particularly following the definition of the UN Sustainable Development Goals (SDGs) for 2030, Nature-Based Solutions (NBS) have gained considerable attention, capturing the interest of both the scientific community and policymakers committed to addressing urban environmental issues. However, the need for studies to guide decision-makers in identifying suitable locations for NBS i

Maximizing the performance of crystal monochromators is a key aspect in the design of beamline optics for diffraction-limited synchrotron sources. Temperature and deformation of cryo-cooled crystals, illuminated by high-power beams of X-rays, can be estimated with a purely analytical model. The analysis is based on the thermal properties of cryo-cooled silicon crystals and the cooling geometry. De

Sustainable and resilient infrastructure projects are necessary for Africa if the continent is to be successful in achieving the Sustainable Development Goals (SDGs) and agenda 2063 of the African Union (AU). The paradigm shift towards a low-carbon society cannot be achieved without sustainable and efficient infrastructure that can withstand the effects of climate change. This chapter discusses th