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The adoption of the Council Directive 2013/59/EURATOM into Austrian national law generated new challenges for businesses, authorities and measurement services. The law defines radon priority regions in which all employers are obliged to hire an authorised radon-monitoring service to determine radon activity concentration at workplaces in basements and on ground floors. In this paper, an overview of our experiences with the process of becoming an accredited and authorised radon-monitoring body using integrating and time-resolved radon measurement equipment is given. The main challenges to overcome, such as determination of measurement uncertainty, conducting metrologically traceable calibration of the track-etch detector system, information not covered by ISO 11665-1, ISO 11665-4 and ISO 11665-5, availability of proficiency tests, etc., are described. This paper aims to be a guideline for laboratories seeking accreditation in the field of radon activity concentration measurements.

After the discovery of aerial embryonic incubation in mudskippers, it was found that the male induces larval hatching by removing the air from the egg-chamber so that the eggs immerse in water. Do the adults provide additional support to the newly hatched larvae to help them leave the life-endangering hypoxic water inside the burrow? This paper compares 18 hatching events of 3 species: dusky gilled mudskipper, Pearse´s mudskipper and slender mudskipper. After air removal 3 different burrow-shape dependent strategies of paternal help for larval burrow leaving were observed: (1) very frequent diving toward the burrow shaft or into the egg-chamber to generate turbulences that can help to propel the larvae toward the water surface; (2) tail-undulation to create a water current out of the burrow that would take along the hatched larvae; and (3) intake of larvae into the paternal mouth, subsequently spitting them out to expel them from the burrow.

AimsThe aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture.MethodsData collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching.ResultsOverall in 13,612 cases of intracapsular femoral neck fracture, 9,110 (66.9%) HAs and 4,502 (33.1%) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared with uncemented fixated prosthesis (p = 0.013). In patients with THA no statistical difference between cemented and uncemented prosthesis was registered, however after one year 2.4% of infections were detected in uncemented and 2.1% in cemented THA. In the subpopulation of HA after one year, 1.9% of infections were registered in cemented and 2.8% in uncemented HA. BMI (p = 0.001) and Elixhauser Comorbidity Index (p < 0.003) were identified as risk factors of periprosthetic joint infection (PJI), while in THA cemented prosthesis also demonstrated an increased risk within the first 30 days (hazard ratio (HR) = 2.73; p = 0.010).ConclusionThe rate of infection after intracapsular femoral neck fracture was statistically significantly reduced in patients treated by antibiotic-loaded cemented HA. Particularly for patients with multiple risk factors for the development of a PJI, the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection.Cite this article: Bone Joint Res 2023;12(5):331–338.

Background: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. Methods: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan ( Bgn ), Tlr3 , and IFN-α/β receptor alpha chain ( Ifnar1 )–deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. Results: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn −/− , Tlr3 −/− , and Ifnar1 −/− mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1–BGN–TLR3–interferon-α/β receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. Conclusions: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

Paresis after spinal cord injury (SCI) is caused by damage to upper and lower motoneurons (LMNs) and may differentially impact neurological recovery. This prospective monocentric longitudinal observational study investigated the extent and severity of LMN dysfunction and its impact on upper extremity motor recovery after acute cervical SCI. Pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials recorded by needle electromyography (EMG) were taken as parameters for LMN dysfunction and its relation to the extent of myelopathy in the first available spine magnetic resonance imaging (MRI) was determined. Motor recovery was assessed by standardized neurological examination within the first four weeks (acute stage) and up to one year (chronic stage) after injury. Eighty-five muscles of 17 individuals with cervical SCI (neurological level of injury from C1 to C7) and a median age of 54 (28-59) years were examined. The results showed that muscles with signs of LMN dysfunction peaked at the lesion center (Χ2 [2, n = 85] = 6.6, p = 0.04) and that the severity of LMN dysfunction correlated with T2-weighted hyperintense MRI signal changes in routine spine MRI at the lesion site (Spearman ρ = 0.31, p = 0.01). Muscles exhibiting signs of LMN dysfunction, as indicated by pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials, were associated with more severe paresis in both the acute and chronic stages after SCI (Spearman ρ acute = -0.22, p = 0.04 and chronic = -0.31, p = 0.004). Moreover, the severity of LMN dysfunction in the acute stage was also associated with a greater degree of paresis (Spearman ρ acute = -0.24, p = 0.03 and chronic = -0.35, p = 0.001). While both muscles with and without signs of LMN dysfunction were capable of regaining strength over time, those without LMN dysfunctions had a higher potential to reach full strength. Muscles with signs of LMN dysfunction in the acute stage displayed increased amplitudes of motor unit action potentials with chronic-stage needle EMG, indicating reinnervation through peripheral collateral sprouting as compensatory mechanism (Χ2 [1, n = 72] = 4.3, p = 0.04). Thus, LMN dysfunction represents a relevant factor contributing to motor impairment and recovery in acute cervical SCI. Defined recovery mechanisms (peripheral reinnervation) may at least partially underlie spontaneous recovery in respective muscles. Therefore, assessment of LMN dysfunction could help refine prediction of motor recovery after SCI.

Microbial maturation disrupted by early life dysbiosis has been linked with increased asthma risk and severity, however the immunological mechanisms underpinning this connection are poorly understood. We sought to understand how delaying microbial maturation drives worsened asthma outcomes later in life and its long-term durability. Drinking water was supplemented with antibiotics on postnatal days 10-20. To assess the immediate and long-term effects of delaying microbial maturation on experimental asthma, we initiated house dust mite exposure when bacterial diversity was either at a minimum or had recovered. Airway hyperresponsiveness, histology, pulmonary leukocyte recruitment, flow cytometric analysis of cytokine producing lymphocytes, and assessment of serum IgG1 and IgE levels were performed. RT-PCR was used to measure IL-13-induced gene expression in sequentially sorted mesenchymal, epithelial, endothelial and leukocyte cell populations from the lung. Delayed microbial maturation increased allergen driven airway hyperresponsiveness and Th17 frequency compared to allergen exposed control mice, even when allergen exposure began after bacterial diversity recovered. Blockade of IL-17A reversed the airway hyperresponsiveness phenotype. Additionally, allergen exposure in animals that experienced delayed microbial maturation showed signs of synergistic signaling between IL-13 and IL-17A in the pulmonary mesenchymal compartment. Delaying microbial maturation in neonates promotes the development of more severe asthma by increasing Th17 frequency, even if allergen exposure is initiated weeks after microbial diversity is normalized. Additionally, IL-17A-aggravated asthma is associated with increased expression of IL-13-induced genes in mesenchymal, but not epithelial cells.

Deoxynivalenol (DON), a type B trichothecene mycotoxin contaminating grain, promotes nausea, emesis, and anorexia. With DON exposure, circulating levels of intestinally derived satiation hormones, including glucagon-like peptide 1 (GLP-1), are elevated. To directly test whether GLP-1 signaling mediates the effects of DON, we examined the response of GLP-1 or GLP-1R-deficient mice to DON injection. We found comparable anorectic and conditioned taste avoidance learning responses in GLP-1/GLP-1R-deficient mice compared with control littermates, suggesting that GLP-1 is not necessary for the effects of DON on food intake and visceral illness. We then used our previously published data from translating ribosome affinity purification with RNA sequencing (TRAP-seq) analysis of area postrema neurons that express the receptor for the circulating cytokine growth differentiation factor (GDF15), GDNF family receptor α-like (GFRAL). Interestingly, this analysis showed that a cell surface receptor for DON, a calcium-sensing receptor (CaSR), is heavily enriched in GFRAL neurons. Given that GDF15 potently reduces food intake and can cause visceral illness by signaling through GFRAL neurons, we hypothesized that DON may also signal by activating CaSR on GFRAL neurons. Indeed, circulating GDF15 levels are elevated after DON administration, but both GFRAL knockout and GFRAL neuron-ablated mice exhibited similar anorectic and conditioned taste avoidance responses compared with WT littermates. Thus, GLP-1 signaling and GFRAL signaling and neurons are not required for DON-induced visceral illness or anorexia.

Assessment of vancomycin-resistant Enterococcus faecium (VREfm) prevalence upon hospital admission and analysis of risk factors for colonization.From 2014 to 2018, patients were recruited within 72 hours of admission to seven participating German university hospitals, screened for VREfm and questioned for potential risk factors (prior multidrug-resistant organism detection, current/prior antibiotic consumption, prior hospital, rehabilitation or long-term care facility stay, international travel, animal contact and proton pump inhibitor [PPI]/antacid therapy). Genotype analysis was done using cgMLST typing. Multivariable analysis was performed.In 5 years, 265 of 17,349 included patients were colonized with VREfm (a prevalence of 1.5%). Risk factors for VREfm colonization were age (adjusted OR [aOR], 1.02; 95% CI, 1.01-1.03), previous (aOR, 2.71; 95% CI, 1.87-3.92) or current (aOR, 2.91; 95% CI, 2.60-3.24) antibiotic treatment, prior multidrug-resistant organism detection (aOR, 2.83; 95% CI, 2.21-3.63), prior stay in a long-term care facility (aOR, 2.19; 95% CI, 1.62-2.97), prior stay in a hospital (aOR, 2.91; 95% CI, 2.05-4.13) and prior consumption of PPI/antacids (aOR, 1.29; 95% CI, 1.18-1.41). Overall, the VREfm admission prevalence increased by 33% each year and 2% each year of life. 250 of 265 isolates were genotyped and 141 (53.2%) of the VREfm were the emerging ST117. Multivariable analysis showed that ST117 and non-ST117 VREfm colonized patients differed with respect to admission year and prior multidrug-resistant organism detection.Age, healthcare contacts and antibiotic and PPI/antacid consumption increase the individual risk of VREfm colonization. The VREfm admission prevalence increase in Germany is mainly driven by the emergence of ST117.

Objective: Contaminated blood cultures result in extended hospital stays and extended durations of antibiotic therapy. Rapid molecular-based blood culture testing can speed positive culture detection and improve clinical outcomes, particularly when combined with an antimicrobial stewardship program. We investigated the impact of a multiplex polymerase chain reaction (PCR) FilmArray Blood Culture Identification (BCID) system on clinical outcomes associated with contaminated blood cultures. Methods: We conducted a retrospective cohort study involving secondary data analysis at a single institution. In this before-and-after study, patients with contaminated blood cultures in the period before PCR BCID was implemented (ie, the pre-PCR period; n = 305) were compared to patients with contaminated blood cultures during the period after PCR BCID was implemented (ie, the post-PCR implementation period; n = 464). The primary exposure was PCR status and the main outcomes of the study were length of hospital stay and days of antibiotic therapy. Results: We did not detect a significant difference in adjusted mean length of hospital stay before (10.8 days; 95% confidence interval [CI], 9.8–11.9) and after (11.2 days; 95% CI, 10.2–12.3) the implementation of the rapid BCID panel in patients with contaminated blood cultures (P = .413). Likewise, adjusted mean days of antibiotic therapy between patients in pre-PCR group (5.1 days; 95% CI, 4.5–5.7) did not significantly differ from patients in post-PCR group (5.3 days; 95% CI, 4.8–5.9; P = .543). Conclusion: The introduction of a rapid PCR-based blood culture identification system did not improve clinical outcomes, such as length of hospital stay and duration of antibiotic therapy, in patients with contaminated blood cultures.

Purpose We aimed to evaluate the long-term impact of the treatment of pyogenic vertebral osteomyelitis (VO) on functional outcomes and patients' quality of life (QoL) with a special focus on psychological well-being. Methods A total of 156 patients with VO with a minimum clinical follow-up of 12 months were retrospectively identified and asked to participate. Patient-reported outcome measures were evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data. Spine-specific outcomes were assessed with the Core Outcome Measure Index and the Oswestry disability index (ODI) or the Neck disability index (NDI), respectively. Results From n = 156 eligible patients, n = 129 patients could be contacted and n = 40 returned questionnaires, yielding a response rate of 31.0%. The mean time from hospital discharge to follow-up was 83.0 ± 3.8 (13–193) months. Spine-specific outcomes showed mild to moderate disability. The mean physical health component score of the SF-36 (37.1 ± 16.7), the mean mental health component score (38.2 ± 14.0) and the mean EQ-5D VAS rating (57.1 ± 21.5) were significantly lower in comparison with the scores of an age-matched reference population (all p Conclusion Even almost seven years on average after completed treatment of VO, patients report impaired QoL. Assessment of psychological disorders should be implemented in clinical practice and future prospective studies.

PURPOSE OF REVIEW: Shoulder instability in patients with underlying joint hyperlaxity can be challenging to treat. Poorly defined terminology, heterogeneous treatments, and sparse reports on clinical outcomes impair the development of best practices in this patient population. This article provides a review of the current literature regarding optimal management of patients suffering from shoulder instability with concomitant hyperlaxity of the shoulder, from isolated shoulder joint hyperlaxity to congenital hypermobility spectrum disorders (HSD). RECENT FINDINGS: Current research shows specialized physiotherapy protocols focused on strengthening of periscapular muscles and improvement of sensorimotor control are a promising non-surgical therapeutic avenue in certain patients, which can be augmented by device-based intervention in select cases. If surgical treatment is warranted, arthroscopic techniques such as pancapsular shift or plication continue to demonstrate favorable outcomes and are currently considered the benchmark for success. The long-term success of more recent innovations such as coracoid process transfers, conjoint tendon transfers, subscapularis tendon augmentation, and capsular reconstruction remains unproven. For patients affected by connective tissue disorders, treatment success is generally less predictable, and the entire array of non-operative and operative interventions needs to be considered to achieve the best patient-specific treatment results. SUMMARY: In the treatment of shoulder instability and concomitant hyperlaxity, specialized physiotherapy protocols augmented by device-based interventions have emerged as powerful, non-operative treatment options for select patients. Successful surgical approaches have been demonstrated to comprehensively address capsular redundancy, labral lesions, and incompetence of additional passive stabilizers in a patient-specific fashion, respective of the underlying connective tissue constitution.

ZusammenfassungIn den letzten Jahren hat die Charakterisierung der Speicheldrüsenkarzinome einen großen Wandel durchlebt. Morphologisch definierte Entitäten konnten zu einem Großteil auch molekular mit einem oftmals distinkten Genotyp charakterisiert werden. Der erste Teil des Artikels gibt einen Überblick über die Fortschritte der molekularen Charakteristiken des Mukoepidermoidkarzinoms, adenoid-zystischen Karzinoms, Azinuszellkarzinoms, des sekretorischen und intraduktalen Karzinoms sowie des hyalinisierenden klarzelligen Karzinoms. Der molekulare Genotyp kann dabei insbesondere bei der Klassifizierung ungewöhnlicher morphologischer Varianten von großem Nutzen sein. Rekurrente NTRK- oder RET-Genfusionen können dabei nicht nur als diagnostisches Hilfsmittel, sondern auch für eine potenzielle gezielte Therapie genutzt werden.

SummaryChimeric antigen receptor (CAR) T cell therapies offer a promising new therapeutic option for treating B cell malignancies, for instance relapsed or refractory diffuse large B cell lymphoma (DLBCL). However, patient access to this type of cellular immunotherapy may be limited due to systemic barriers even in wealthy Western countries. In Austria, the CAR T eligible DLBCL population is estimated to encompass approximately 56 patients based on the criteria applied for CAR T registrational trials. However, less than 40% of these DLBCL patients eligible for commercial standard-of-care CAR T cell therapy were finally treated with CAR T cell therapy in 2021 based on our analysis. This report discusses potential barriers that may impede current patient access to CAR T cell therapy and provides recommendations for systemic solutions to address these barriers and improve the CAR T access situation in Austria.

INTRODUÇÃO: O aleitamento materno oferece benefícios tanto para a saúde do recém-nascido quanto para a mãe, sendo essencial que esta prática inicie ainda na primeira hora pós-parto. OBJETIVO: Descrever as estratégias e características facilitadoras para o aleitamento materno na primeira hora de vida do recém-nascido. MÉTODO: Trata-se de estudo de revisão narrativa. O levantamento bibliográfico foi realizado na base de dados da Biblioteca Virtual em Saúde (BVS), nas bases de dados: LILACS e MEDLINE, utilizando os descritores “Enfermagem Obstétrica” AND “Aleitamento Materno” AND “Recém-Nascido”, utilizando o operador booleano “AND”. Para análise dos dados utilizou-se a estratégia da análise de conteúdo, com ênfase para as respostas à pergunta de estudo. RESULTADO: Com base nas produções analisadas, enfatizou alguns métodos facilitadores para a prática do aleitamento materno na primeira hora de vida do recém-nascido, como, a prática do contato pele a pele, a importância do papel da enfermagem, seja na sala de parto, quanto nas assistências prestadas antes, durante e o pós-parto. Outras características citadas trazem referências às condições clínicas do recém-nascido, além de um ambiente propício para realização desta prática de contato inicial entre mãe e filho. CONCLUSÃO: Os métodos que se sobressaem consistem no contato pele a pele e assistência de enfermagem, ressaltando a importância de uma qualificação destes profissionais para que esta prática possa tornar-se mais frequente em nossa sociedade, visto a importância desta prática para saúde materno infantil.

Background: Recent evidence questions the role of medial opening wedge high tibial osteotomy (mowHTO) in the correction of femoral-based varus malalignment because of the potential creation of an oblique knee joint line. However, the clinical effectiveness of alternatively performing an isolated lateral closing wedge distal femoral osteotomy (lcwDFO), in which the mechanical unloading effect in knee flexion may be limited, is yet to be confirmed. Purpose/Hypothesis: The purpose of this article was to compare clinical outcomes between patients undergoing varus correction via isolated lcwDFO or mowHTO, performed according to the location of the deformity, in a cohort matched for confounding variables. It was hypothesized that results from undergoing isolated lcwDFO for symptomatic varus malalignment would not significantly differ from the results after mowHTO. Study Design: Cohort study; Level of evidence, 3. Methods: Consecutive patients who underwent isolated mowHTO or lcwDFO according to a tibial- or femoral-based symptomatic varus deformity between January 2010 and October 2019 were enrolled. Confounding factors, including age at surgery, sex, body mass index, preoperative femorotibial axis, and postoperative follow-up, were matched using propensity score matching. The International Knee Documentation Committee (IKDC) Subjective Knee Form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Tegner Activity Scale, and visual analog scale (VAS) for pain were collected preoperatively and at a minimum of 24 months postoperatively. Results: Of 535 knees assessed for eligibility, 50 knees (n = 50 patients, n = 25 per group) were selected by propensity score matching. Compared with preoperatively, both the mowHTO group (IKDC, 55.1 ± 16.5 vs 71.3 ± 14.7, P = .002; WOMAC, 22.0 ± 18.0 vs 9.6 ± 10.8, P < .001; Lysholm, 55.2 ± 23.1 vs 80.7 ± 16, P < .001; VAS, 4.1 ± 2.4 vs 1.6 ± 1.8, P < .001) and the lcwDFO group (IKDC, 49.4 ± 14.6 vs 66 ± 20.1, P = .003; WOMAC, 25.2 ± 17.0 vs 12.9 ± 17.6, P = .003; Lysholm, 46.5 ± 15.6 vs 65.4 ± 28.7, P = .011; VAS, 4.5 ± 2.2 vs 2.6 ± 2.5, P = .001) had significantly improved at follow-up (80 ± 20 vs 81 ± 43 months). There were no significant differences between the groups at baseline, at final follow-up, or in the amount of clinical improvement in any of the outcome parameters ( P > .05; respectively). Conclusion: Performing both mowHTO or lcwDFO yields significant improvement in clinical outcomes if performed at the location of the deformity of varus malalignment. These findings confirm the clinical effectiveness of performing an isolated lcwDFO in femoral-based varus malalignment, which is comparable with that of mowHTO in the correction of varus malalignment.

ZusammenfassungDer zweite Teil des Artikels widmet sich den molekularen Charakteristiken des epithelial-myoepithelialen Karzinoms, des polymorphen Adenokarzinoms, des myoepithelialen Karzinoms, des Basalzelladenokarzinoms sowie des Speichelgangkarzinoms. Zusätzlich werden die neu aufgekommenen Entitäten des muzinösen Adenokarzinoms, des sklerosierenden mikrozystischen Adenokarzinoms und des mikrosekretorischen Adenokarzinoms zusammengefasst. Auch bei den meisten dieser Entitäten kann der molekulare Genotyp diagnostisch sehr hilfreich sein. Eine Überexpression des Androgenrezeptors und/oder von „human epidermal growth factor receptor 2“ (HER2)/neu kann dabei im geeigneten histopathologischen Kontext nicht nur zur Diagnoseuntermauerung eines Speichelgangkarzinoms dienen, sondern potenziell auch gezielt therapeutisch angegangen werden.

Aims Distraction osteogenesis with intramedullary lengthening devices has undergone rapid development in the past decade with implant enhancement. In this first single-centre matched-pair analysis we focus on the comparison of treatment with the PRECICE and STRYDE intramedullary lengthening devices and aim to clarify any clinical and radiological differences. Methods A single-centre 2:1 matched-pair retrospective analysis of 42 patients treated with the STRYDE and 82 patients treated with the PRECICE nail between May 2013 and November 2020 was conducted. Clinical and lengthening parameters were compared while focusing radiological assessment on osseous alterations related to the nail’s telescopic junction and locking bolts at four different stages. Results Osteolysis next to the telescopic junction was observed in 31/48 segments (65%) lengthened with the STRYDE nail before implant removal compared to 1/91 segment (1%) in the PRECICE cohort. In the STRYDE cohort, osteolysis initially increased, but decreased or resolved in almost all lengthened segments (86%) after implant removal. Implant failure was observed in 9/48 STRYDE (19%) and in 8/92 PRECICE nails (9%). Breakage of the distal locking bolts was found in 5/48 STRYDE nails (10%) compared to none in the PRECICE cohort. Treatment-associated pain was generally recorded as mild and found in 30/48 patients (63%) and 39/92 (42%) in the STRYDE and PRECICE cohorts, respectively. Temporary range of motion (ROM) limitations under distraction were registered in 17/48 (35%) segments treated with the STRYDE and 35/92 segments (38%) treated with the PRECICE nail. Conclusion Osteolysis and periosteal reaction, implant breakage, and pain during lengthening and consolidation is more likely in patients treated with the STRYDE nail compared to the PRECICE nail. Temporary ROM limitations during lengthening occurred independent of the applied device. Implant-related osseous alterations seem to remodel after implant removal. Cite this article: Bone Joint J 2023;105-B(1):88–96.

BackgroundSuccessful utilization of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) requires a comprehensive understanding of its rules, terminology, and several complex concepts. There have been no studies investigating classification accuracy since the newest ISNCSCI revision (2019).ObjectivesTo evaluate classification accuracy of SCI professionals using the 2019 ISNCSCI edition, identify common mistakes and areas of confusion, and assess associations between experience in ISNCSCI classification and performance.MethodsMembers of the International Spinal Cord Society (ISCoS) and attendees of the ISCoS Annual Scientific Meeting 2021 were invited to complete an online survey that included six ISNCSCI cases to classify.ResultsA total of 107 persons completed the survey, with overall classification accuracy of 74.6%. Accuracy was highest for injury completeness (95.3%) and sensory level (91.1%) and lowest for motor zone of partial preservation (ZPP; 54.7%) and ASIA Impairment Scale (AIS) grade (57.3%). Newer concepts, including the appropriate documentation of non-SCI conditions and classification of ZPP in incomplete injuries, contributed to several common errors. There was a significant association between overall classification accuracy and self-rated experience in the ISNCSCI classification (p = .017). Experience with the ISNCSCI examination, experience in SCI medicine, and occupation were not found to be significantly associated with overall classification accuracy.ConclusionClassification accuracy of an international cohort of SCI professionals was modest but greater than previous reports. Knowledge deficits about the 2019 ISNCSCI updates are prevalent and contribute to common classification errors. Further training in the utilization of the ISNCSCI is needed.

Kaum eine gastroenterologische Erkrankung wird so intensiv diskutiert wie das Reizdarmsyndrom (RDS). Was vor einigen Jahrzehnten das unbefriedigende Ergebnis einer Ausschlussdiagnose war, ist mittlerweile eine ernstzunehmende Erkrankung mit definierten Diagnosekriterien und wirksamen Therapieoptionen, die in der aktuellen Leitlinie ausführlich dargelegt sind. Die Pathogenese ist multifaktoriell und wird zunehmend besser verstanden. Heute ordnet man das Reizdarmsyndrom als Störung der Darm-Hirn-Interaktionen ein.

Background: Identifying novel biomarkers that are both specific and sensitive to periprosthetic joint infection (PJI) has the potential to improve diagnostic accuracy and ultimately enhance patient outcomes. Therefore, the aim of this systematic review is to identify and evaluate the effectiveness of novel biomarkers for the diagnosis of PJI. Methods: We searched the MEDLINE, EMBASE, PubMed, and Cochrane Library databases from January 1, 2018, to September 30, 2022, using the search terms “periprosthetic joint infection,” “prosthetic joint infection,” or “periprosthetic infection” as the diagnosis of interest and the target index, combined with the term “marker.” We excluded articles that mentioned established biomarkers such as CRP, ESR, Interleukin 6, Alpha defensin, PCT (procalcitonin), and LC (leucocyte cell count). We used the MSIS, ICM, or EBJS criteria for PJI as the reference standard during quality assessment. Results: We collected 19 studies that analyzed fourteen different novel biomarkers. Proteins were the most commonly analyzed biomarkers (nine studies), followed by molecules (three studies), exosomes (two studies), DNA (two studies), interleukins (one study), and lysosomes (one study). Calprotectin was a frequently analyzed and promising marker. In the scenario where the threshold was set at ≥50-mg/mL, the calprotectin point-of-care (POC) performance showed a high sensitivity of 98.1% and a specificity of 95.7%. Conclusion: None of the analyzed biomarkers demonstrated outstanding performance compared to the established parameters used for standardized treatment based on established PJI definitions. Further studies are needed to determine the benefit and usefulness of implementing new biomarkers in diagnostic PJI settings.

Data-driven engineering refers to systematic data collection and processing using machine learning to improve engineering systems. Currently, the implementation of data-driven engineering relies on fundamental data science and software engineering skills. At the same time, model-based engineering is gaining relevance for the engineering of complex systems. In previous work, a model-based engineering approach integrating the formalization of machine learning tasks using the general-purpose modeling language SysML is presented. However, formalized machine learning tasks still require the implementation in a specialized programming languages like Python. Therefore, this work aims to facilitate the implementation of data-driven engineering in practice by extending the previous work of formalizing machine learning tasks by integrating model transformation to generate executable code. The method focuses on the modifiability and maintainability of the model transformation so that extensions and changes to the code generation can be integrated without requiring modifications to the code generator. The presented method is evaluated for feasibility in a case study to predict weather forecasts. Based thereon, quality attributes of model transformations are assessed and discussed. Results demonstrate the flexibility and the simplicity of the method reducing efforts for implementation. Further, the work builds a theoretical basis for standardizing data-driven engineering implementation in practice.

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2–19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9–not reached), with 54.2% (95% CI: 40.8–65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020–0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.

This research investigated the durability of fiber anchors in bond-critical CFRP systems for concrete structures. While the durability of CFRP and CFRP-concrete bond is well-studied, the durability of fiber anchors in typical bond-critical applications remains unexplored. To address this gap, fiber anchors were tested in 152×152×508-mm notched beams strengthened with CFRP. Accelerated conditioning involved 3,000 hours of water immersion at 50 °C. Results revealed up to 24% capacity loss in specimens with anchor rupture as the failure mode, while no capacity loss was observed in specimens failing due to flexural CFRP rupture., Paper 66

Aims: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. Design, Setting and Participants: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. Measurements: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. Findings: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. Conclusions: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options., Medical Research Future Fund (MRFF) MRF1141214, National Health and Medical Research Council (NHMRC) of Australia GNT2009464

Zusammenfassung Einführung Inhalatives Rauchen ist mit erheblicher Morbidität und Mortalität sowie einer signifikanten Belastung der Gesundheitsökonomie verbunden. Der möglichst frühe Rauchstopp ist daher medizinisch und gesundheitsökonomisch von herausragender Bedeutung. Mit dem aktuellen Goldstandard der Tabakentwöhnung, einer kombinierten verhaltenstherapeutischen und medikamentösen Unterstützung, werden bevölkerungsbezogen nur unzureichend viele Raucher erreicht. Leitlinienkonforme, niederschwellige und breit verfügbare digitale Entwöhnungsangebote könnten dagegen die Zahl erfolgreicher Aufhörer signifikant steigern. Mit dem digitalen Entwöhnungsprogramm „Nichtraucherhelden“ (Online-Version und Smartphone-App) steht seit 2016 eine solche leitlinienkonforme und niederschwellige digitale Tabakentwöhnung zur Verfügung. Das Programm besteht aus 2 Vorbereitungs- und 10 Programmtagen und umfasst die Kerninhalte gängiger Tabakentwöhnungskurse. Probanden und Methodik Die vorliegende Studie untersuchte die Programmteilnehmer im Zeitraum von Dez. 2016 bis Nov. 2019 (n = 2491) retrospektiv in Bezug auf Akzeptanz, Adhärenz und Effektivität. 69 % der TN waren weiblich, das Durchschnittsalter betrug 46 Jahre. Ergebnisse Der Rauchstopptag wurde im Durchschnitt nach knapp 19 Tagen erreicht. Die Aufhörquote nach einem Jahr lag bei 15 %. Unerwartet war die höhere Aufhörquote stärker abhängiger Raucher im Vergleich zu weniger stark Abhängigen. Folgerung Die Untersuchung zeigt die prinzipielle Durchführbarkeit und Wirksamkeit eines digitalen, leitlinienkonformen Entwöhnungsprogramms. Zur Bestätigung der Effektivität ist eine randomisierte, kontrollierte Studie erforderlich.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

This study examines when firms offer higher product quality. We measure product quality by examining four different inflight amenities provided by airlines: Wi-Fi, seat size, entertainment, and seat power. Using daily flight level data for over 800 routes and spanning nine weeks in third quarter of 2015 we observe that carriers were actively retrofitting aircraft to expand their inflight amenity offerings. We find significantly lower product quality (Wi-Fi, entertainment, and power) on more concentrated routes. While considerable research has been done on airline pricing, less well known is how airlines pursue other revenue streams from ancillary services. Recent work by Brueckner et al. (2015) explores the role of baggage fees in airline pricing. We examine additional revenue streams provided by Wi-Fi and entertainment inflight amenities. We find that carriers are lowering the posted base ticket prices on routes with Wi-Fi and entertainment and then charging passengers for using these amenities. The IV price estimates reveal that magnitude of the posted fare reduction is larger than the additional revenue generated from the inflight amenity.

50 Pág., In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratifcation vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV, This work was supported in part through Laulima Govern ment Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Gov ernment Solutions, LLC under Contract No. HHSN272201800013C. This work was also funded in part by Contract No. HSHQDC 15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges support from the Mississippi Agri cultural and Forestry Experiment Station (MAFES), USDA-ARS pro ject 58-6066-9-033 and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project, under Accession Num ber 1021494.