Growth of organic crystalline thin films with strong second-order nonlinearity for integrated optics

We demonstrate the growth of highly nonlinear crystalline thin films of N-benzyl-2-methyl-4-nitroaniline (BNA) with a controllable crystal orientation. These films are obtained by crystallizing the material in a temperature gradient. Through second-harmonic generation experiments at a fundamental wavelength of 1550 nm, we found a second-order nonlinearity of (153 ± 70) pm/V. This greatly exceeds the value of 54 pm/V for LiNbO3, the benchmark nonlinear crystal. Moreover, the crystalline films are grown on amorphous substrates with processing temperatures not exceeding 115°C, making them suitable for back-end photonic integration on a CMOS chip. We envisage the growth of BNA crystalline films on silicon nitride photonic integrated circuits, where a strong second-order nonlinearity is lacking

Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional Factor VIII Dosing in Hemophilia A Prophylaxis

The total body weight-based dosing strategy currently used in the prophylactic treatment of hemophilia A may not be appropriate for all populations. The assumptions that guide weight-based dosing are not valid in overweight and obese populations, resulting in overdosing and ineffective resource utilization. We explored different weight metrics including lean body weight, ideal body weight, and adjusted body weight to determine an alternative dosing strategy that is both safe and resource-efficient in normal and overweight/obese adult patients. Using a validated population pharmacokinetic model, we simulated a variety of dosing regimens using different doses, weight metrics, and frequencies; we also investigated the implications of assuming various levels of endogenous factor production. Ideal body weight performed the best across all of the regimens explored, maintaining safety while moderating resource consumption for overweight and obese patients.Canadian HIV Trials NetworkCanadian Institutes of Health Researc

Hemophilia treatment in 2021: choosing the”optimal” treatment using an integrative, patient-oriented approach to shared decision-making between patients and clinicians

The mainstay of hemophilia treatment is to prevent bleeding through regular long-term prophylaxis and to control acute breakthrough bleeds. Various treatment options are currently available for prophylaxis, and treatment decision-making is a challenging and multifaceted process of identifying the most appropriate option for each patient. A multidisciplinary expert panel convened to develop a practical, patient-oriented algorithm to facilitate shared treatment decision-making between clinicians and patients. Key variables were identified, and an algorithm proposed based on five variables: bleeding phenotype, musculoskeletal status, treatment adherence, venous access, and lifestyle. A complementary, patient-focused preference tool was also hypothesized, with the aim of exploring individual patients' priorities, preferences, and goals. It is hoped that the proposed algorithm and the hypothesized patient preference tool will assist in selecting a treatment for each patient that is as efficient as possible in preventing bleeds while also accounting for the patient's expectations and prioritiesFunded by a grant from Novo Nordis

Panton-Valentine Leukocidin Does Play a Role in the Early Stage of Staphylococcus aureus Skin Infections: A Rabbit Model

Despite epidemiological data linking necrotizing skin infections with the production of Panton-Valentine leukocidin (PVL), the contribution of this toxin to the virulence of S. aureus has been highly discussed as a result of inconclusive results of in vivo studies. However, the majority of these results originate from experiments using mice, an animal species which neutrophils - the major target cells for PVL - are highly insensitive to the action of this leukocidin. In contrast, the rabbit neutrophils have been shown to be as sensitive to PVL action as human cells, making the rabbit a better experimental animal to explore the PVL role. In this study we examined whether PVL contributes to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits were injected intradermally with 108 cfu of either a PVL positive community-associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or a PVL complemented knockout strain, and the development of skin lesions was observed. While all strains induced skin infection, the wild type strain produced larger lesions and a higher degree of skin necrosis compared to the PVL knockout strain in the first week after the infection. The PVL expression in the rabbits was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies observed only in the rabbits infected with PVL positive strains. These results indicate that the rabbit model is more suitable for studying the role of PVL in staphylococcal diseases than other animal models. Further, they support the epidemiological link between PVL producing S. aureus strains and necrotizing skin infections

PROBA-3 mission and the Shadow Position Sensors: Metrology measurement concept and budget

PROBA-3 is a space mission of the European Space Agency that will test, and validate metrology and control systems for autonomous formation flying of two independent satellites. PROBA-3 will operate in a High Elliptic Orbit and when approaching the apogee at 6·104 Km, the two spacecraft will align to realize a giant externally occulted coronagraph named ASPIICS, with the telescope on one satellite and the external occulter on the other one, at inter-satellite distance of 144.3 m. The formation will be maintained over 6 hrs across the apogee transit and during this time different validation operations will be performed to confirm the effectiveness of the formation flying metrology concept, the metrology control systems and algorithms, and the spacecraft manoeuvring. The observation of the Sun's Corona in the field of view [1.08;3.0]RSun will represent the scientific tool to confirm the formation flying alignment. In this paper, we review the mission concept and we describe the Shadow Position Sensors (SPS), one of the metrological systems designed to provide high accuracy (sub-millimetre level) absolute and relative alignment measurement of the formation flying. The metrology algorithm developed to convert the SPS measurements in lateral and longitudinal movement estimation is also described and the measurement budget summarized

Clinical and molecular epidemiological features of critically ill patients with invasive group A Streptococcus infections: a Belgian multicenter case-series.

peer reviewed[en] BACKGROUND: Recent alerts have highlighted an increase in group A streptococcal (GAS) infections since 2022 in Europe and the United States. Streptococcus pyogenes can cause limited skin or mucosal disease, but can also present as severe invasive disease necessitating critical care. We performed a multicenter retrospective study of patients with GAS infections recently admitted to Belgian intensive care units (ICUs) since January 2022. We describe patient characteristics and investigate the molecular epidemiology of the S. pyogenes strains involved. RESULTS: Between January 2022 and May 2023, a total of 86 cases (56 adults, 30 children) with GAS disease were admitted to critical care in the university hospitals of Leuven, Antwerp and Liège. We noted a strikingly high incidence of severe community-acquired pneumonia (sCAP) (45% of adults, 77% of children) complicated with empyema in 45% and 83% of adult and pediatric cases, respectively. Two-thirds of patients with S. pyogenes pneumonia had viral co-infection, with influenza (13 adults, 5 children) predominating. Other disease presentations included necrotizing fasciitis (23% of adults), other severe skin/soft tissue infections (16% of adults, 13% of children) and ear/nose/throat infections (13% of adults, 13% of children). Cardiogenic shock was frequent (36% of adults, 20% of children). Fifty-six patients (65%) had toxic shock syndrome. Organ support requirements were high and included invasive mechanical ventilation (77% of adults, 50% of children), renal replacement therapy (29% of adults, 3% of children) and extracorporeal membrane oxygenation (20% of adults, 7% of children). Mortality was 21% in adults and 3% in children. Genomic analysis of S. pyogenes strains from 55 out of 86 patients showed a predominance of emm1 strains (73%), with a replacement of the M1global lineage by the toxigenic M1UK lineage (83% of emm1 strains were M1UK). CONCLUSIONS: The recent rise of severe GAS infections (2022-23) is associated with introduction of the M1UK lineage in Belgium, but other factors may be at play-including intense circulation of respiratory viruses and potentially an immune debt after the COVID pandemic. Importantly, critical care physicians should include S. pyogenes as causative pathogen in the differential diagnosis of sCAP

Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick

Background The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process. Results Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross-comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo-acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases. Results One hundred thirty-four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities.</p

‘Haemophilia Guidelines for All’: A new ambition of the World Federation of Haemophilia (WFH)

‘Treatment for all’ is the vision statement of the World Federation of Haemophilia (WFH) which works to improve and sustain care for people with inherited bleeding disorders around the World. 2020 sees the publication of the third edition and latest edition of the WFH haemophilia guidelines, aimed at harmonising the delivery of haemophilia care worldwide.1 Initiated and sponsored by the Federation, the guidelines published as a supplement in the Haemophilia journal represent an extraordinary collaborative effort. It has involved many active members of the Federation and a large international group of expert healthcare professionals from diverse and complementary backgrounds. This third edition of the guidelines is comprehensive and based on rigorous methodology. It is driven by the ambition to improve the overall care, treatment and quality of life of patients with inherited bleeding disorders around the world. The guidelines provide a unique resource of practical, detailed yet concise, holistic and accessible recommendations. [...

The emerging clinical and scientific role of the physiotherapist in haemophilia care

The predominance of joint and muscle bleeding in people with haemophilia means that the consequences of the disorder are mainly musculoskeletal.1 These consequences impact on physical function of upper and lower limbs which in turn limits an individual's ability to perform daily tasks as well as participate fully in all areas of life. In the past decade, there has been a rapid and unprecedented increase in the available medical treatment options for haemophilia, including extended half‐life clotting factor concentrates, non‐replacement therapies such as Emicizumab and gene therapy.2 These advances are likely to enable people with haemophilia with and without inhibitor the potential to lead a more active lifestyle with enhanced physical function as well as lowering bleeding frequency. The subsequent reduction in bleeding frequency may result in more subtle and less clinically evident early signs of arthropathic change. As a consequence, it is very likely that the measurement of the annual bleeding rate will no longer be a sensitive tool for measuring the effectiveness of treatments. [...