What is the appropriate measure of radiology workload: Study or image numbers?

INTRODUCTION: Previous studies assessing the volume of radiological studies rarely considered the corresponding number of images. We aimed to quantify the increases in study and image numbers per radiologist in a tertiary healthcare network to better understand the demands on imaging services. METHODS: Using the Picture Archiving and Communication System (PACS), the number of images per study was obtained for all diagnostic studies reported by in-house radiologists at a tertiary healthcare network in Melbourne, Australia, between January 2009 and December 2022. Payroll data was used to obtain the numbers of full-time equivalent radiologists. RESULTS: Across all modalities, there were 4,462,702 diagnostic studies and 1,116,311,209 images. The number of monthly studies increased from 17,235 to 35,152 (104%) over the study period. The number of monthly images increased from 1,120,832 to 13,353,056 (1091%), with computed tomography (CT) showing the greatest absolute increase of 9,395,653 images per month (1476%). There was no increase in the monthly studies per full-time equivalent radiologist; however, the number of monthly image slices per radiologist increased 399%, from 48,781 to 243,518 (Kendall Tau correlation coefficient 0.830, P-value < 0.0001). CONCLUSION: The number of monthly images per radiologist increased substantially from 2009 to 2022, despite a relatively constant number of monthly studies per radiologist. Our study suggests that using the number of studies as an isolated fundamental data set underestimates the true radiologist's workload. We propose that the increased volume of images examined by individual radiologists may more appropriately reflect true work demand and may add more weight to future workforce planning.

Synthesis, Characterization, and Environmental Applications of Novel Per-Fluorinated Organic Polymers with Azo- and Azomethine-Based Linkers via Nucleophilic Aromatic Substitution.

This study reports on the synthesis and characterization of novel perfluorinated organic polymers with azo- and azomethine-based linkers using nucleophilic aromatic substitution. The polymers were synthesized via the incorporation of decafluorobiphenyl and hexafluorobenzene linkers with diphenols in the basic medium. The variation in the linkers allowed the synthesis of polymers with different fluorine and nitrogen contents. The rich fluorine polymers were slightly soluble in THF and have shown molecular weights ranging from 4886 to 11,948 g/mol. All polymers exhibit thermal stability in the range of 350-500 °C, which can be attributed to their structural geometry, elemental contents, branching, and cross-linking. For instance, the cross-linked polymers with high nitrogen content, DAB-Z-1h and DAB-Z-1O, are more stable than azomethine-based polymers. The cross-linking was characterized by porosity measurements. The azo-based polymer exhibited the highest surface area of 770 m2/g with a pore volume of 0.35 cm3/g, while the open-chain azomethine-based polymer revealed the lowest surface area of 285 m2/g with a pore volume of 0.0872 cm3/g. Porous structures with varied hydrophobicities were investigated as adsorbents for separating water-benzene and water-phenol mixtures and selectively binding methane/carbon dioxide gases from the air. The most hydrophobic polymers containing the decafluorbiphenyl linker were suitable for benzene separation, while the best methane uptake values were 6.14 and 3.46 mg/g for DAB-Z-1O and DAB-A-1O, respectively. On the other hand, DAB-Z-1h, with the highest surface area and being rich in nitrogen sites, has recorded the highest CO2 uptake at 298 K (17.25 mg/g).

Major trauma among E-Scooter and bicycle users: a nationwide cohort study.

OBJECTIVES: To determine the incidence, demographics and injury patterns involved in E-Scooter-related hospital admissions due to significant trauma compared with bicycle-related trauma within England and Wales. To compare morbidity and mortality between groups. DESIGN: A retrospective cohort study based on data which has been prospectively collected and submitted to the UK Trauma Audit and Research Network (TARN) registry. SETTING: Major trauma centres and trauma units within England and Wales. PARTICIPANTS: Patients of any age who were admitted to hospitals in England and Wales with injuries following E-Scooter or bicycle incidents between the dates 1 January 2021-31 December 2021. All patients must have met TARN database inclusion criteria. OUTCOMES: In-hospital mortality, critical care admission and length of stay (LoS), hospital LoS and discharge destination. RESULTS: There were 293 E-Scooter trauma incidents compared with 2538 bicycle incidents. E-Scooter users were more likely to be admitted to a major trauma centre (p=0.019) or a critical care unit (p<0.001). Serious head and limb trauma (Abbreviated Injury Scale >2) occurred more frequently among the E-Scooter cohort (35.2% vs 19.7%, p<0.001 and 39.9% vs 27.2%, p<0.001, respectively) while serious chest and pelvic trauma were greater among bicycle users (p<0.001 and p=0.003, respectively). Over one-third of E-Scooter injuries were incurred outside the current legislation by patients who were intoxicated by alcohol and drugs (26%, 75/293) or under the age of 17 (14%, 41/293). CONCLUSIONS: These early results suggest a greater relative incidence of serious trauma and an alternative pattern of injury among E-Scooter users compared with bicycles. TRIAL REGISTRATION NUMBER: TARN210101.

Alternative pathway activation in pregnancy, a measured amount "complements" a successful pregnancy, too much results in adverse events.

During pregnancy, the maternal host must adapt in order to enable growth of the fetus. These changes affect all organ systems and are designed both to protect the fetus and to minimize risk to the mother. One of the most prominent adaptations involves the immune system. The semi-allogenic fetoplacental unit has non-self components and must be protected against attack from the host. This requires both attenuation of adaptive immunity and protection from innate immune defense mechanisms. One of the key innate immune players is complement, and it is important that the fetoplacental unit is not identified as non-self and subjected to complement attack. Adaptation of the complement response must, however, be managed in such a way that maternal protection against infection is not compromised. As the complement system also plays a significant facilitating role in many of the stages of a normal pregnancy, it is also important that any necessary adaptation to accommodate the semi-allogenic aspects of the fetoplacental unit does not compromise this. In this review, both the physiological role of the alternative pathway of complement in facilitating a normal pregnancy, and its detrimental participation in pregnancy-specific disorders, are discussed.

Effective refractive error coverage in adults aged 50 years and older: estimates from population-based surveys in 61 countries.

BACKGROUND: In 2021, WHO Member States endorsed a global target of a 40-percentage-point increase in effective refractive error coverage (eREC; with a 6/12 visual acuity threshold) by 2030. This study models global and regional estimates of eREC as a baseline for the WHO initiative. METHODS: The Vision Loss Expert Group analysed data from 565 448 participants of 169 population-based eye surveys conducted since 2000 to calculate eREC (met need/[met need + undermet need + unmet need]). A binary logistic regression model was used to estimate eREC by Global Burden of Disease (GBD) Study super region among adults aged 50 years and older. FINDINGS: In 2021, distance eREC was 79·1% (95% CI 72·4-85·0) in the high-income super region; 62·1% (54·7-68·8) in north Africa and Middle East; 49·5% (45·0-54·0) in central Europe, eastern Europe, and central Asia; 40·0% (31·7-48·2) in southeast Asia, east Asia, and Oceania; 34·5% (29·4-40·0) in Latin America and the Caribbean; 9·0% (6·5-12·0) in south Asia; and 5·7% (3·1-9·0) in sub-Saharan Africa. eREC was higher in men and reduced with increasing age. Global distance eREC increased from 2000 to 2021 by 19·0%. Global near vision eREC for 2021 was 20·5% (95% CI 17·8-24·4). INTERPRETATION: Over the past 20 years, distance eREC has increased in each super region yet the WHO target will require substantial improvements in quantity and quality of refractive services in particular for near vision impairment. FUNDING: WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, Brien Holden Vision Institute, Lions Clubs International Foundation.

Biomecánica del pase con borde interno entre futbolistas prejuveniles y juveniles de Formativas y Academia / Biomecânica do passe com bordo interior entre os jogadores de futebol pré-juvenil e juvenil de formação e academia / Biomechanics of the pass with internal edge among prejuvenile and juvenile soccer players of Formative and Academy centers

RESUMEN La biomecánica es una ciencia que ayuda al estudio de los movimientos aplicados en distintos deportes, incluyendo el fútbol, que permite identificar y corregir errores técnicos. Esta es una base fundamental para el control de la preparación del deportista. En tal sentido, se planteó como propósito de la investigación analizar biomecánicamente el pase con borde interno del pie en futbolistas prejuveniles y juveniles de Formativas y Academia. La investigación es de tipo descriptiva-explicativa, de orden correlacional; se diagnostican biomecánicamente a 40 futbolistas en dos grupos independientes (grupo 1: Formativas; grupo 2: Academia; entre 14-18 años). Se analizan diez indicadores, se incluye la edad. Se demostraron diferencias significativas en el indicador "DB" (p=0.000), el indicador "ÁFRA" (p=0.006), el indicador "DPAE" (p=0.000), y los indicadores "VF", "A" y "TE" (p=0.000) respectivamente, mientras que las variables o indicadores "ÁFRE" (p=1.000), "EX" (p=0.102) y "EY" (p=0.056) no presentaron diferencias significativas entre los grupos independientes. En la comparación realizada con los jugadores de un equipo profesional y los jugadores de una Academia de formación, se pudo evidenciar que existen diferencias notables desde la fase inicial del pase con el borde interno del pie, mostrando la distancia del jugador con respecto al balón, así como en la fase previa donde los jugadores de Formativas poseen una mejor ejecución del movimiento técnico; esto se refleja en la fase de contacto donde se evidencia una mayor velocidad y aceleración al momento del impacto con el balón.

RESUMO A biomecânica é uma ciência que ajuda o estudo dos movimentos aplicados em diferentes desportos, incluindo o futebol, o que permite a identificação e correção de erros técnicos. Esta é uma base fundamental para o controlo da preparação do atleta. Neste sentido, o objectivo da investigação era analisar biomecanicamente o passe com a extremidade interna do pé em jogadores de futebol pré-juvenil e juvenil em treino e academia. A investigação é de tipo descritivo-explicativo, de ordem correlativa; 40 jogadores de futebol são diagnosticados biomecanicamente em dois grupos independentes (Grupo 1: Formação; Grupo 2: Academia; entre 14-18 anos de idade). Foram analisados dez indicadores, incluindo a idade. Foram demonstradas diferenças significativas no indicador "DB" (p=0,000), o indicador "ÁFRA" (p=0,006), o indicador "DPAE" (p=0,000), e os indicadores "VF", "A" e "TE" (p=0,000) respectivamente, enquanto que as variáveis ou indicadores "ÁFRE" (p=1,000), "EX" (p=0,102) e "EY" (p=0,056) não apresentavam diferenças significativas entre os grupos independentes. Na comparação feita com os jogadores de uma equipa profissional e com os jogadores de uma academia de treino, constatou-se que existem diferenças notáveis em relação à fase inicial do passe com a borda interior do pé, mostrando a distância do jogador em relação à bola, bem como na fase anterior em que os jogadores da academia de treino têm uma melhor execução do movimento técnico; isto reflete-se na fase de contato onde é evidente uma maior velocidade e aceleração no momento do impacto com a bola.

ABSTRACT Biomechanics is a science that helps the study of movements applied in different sports, including soccer, which allows identifying and correcting technical errors. This is a fundamental basis for the control of the athlete's preparation. In this sense, the purpose of the research was to analyze biomechanically the pass with the inner edge of the foot in pre-juvenile and youth soccer players of training and academy. The research is of descriptive-explanatory type, of correlational order; 40 soccer players were biomechanically diagnosed in two independent groups (Group 1: Formative; Group 2: Academy; between 14-18 years). Ten indicators are analyzed, including age. Significant differences were demonstrated in the "DB" indicator (p=0.000), the "ÁFRA" indicator (p=0.006), the "DPAE" indicator (p=0.000), and the "VF", "A" and " TE" (p=0.000) respectively, while the variables or indicators "ÁFRE" (p=1.000), "EX" (p=0.102) and "EY" (p=0.056) did not present significant differences between the independent groups. In the comparison made with the players of a professional team and the players of a training academy, it was possible to show that there are notable differences from the initial phase of the pass with the inner edge of the foot, showing the distance of the player with respect to the ball, as well as in the previous phase where the players in formatiom have a better execution of the technical movement; this is reflected in the contact phase where greater speed and acceleration are evident at the moment of impact with the ball.

Heteroatom-Doped Porous Carbons as Effective Adsorbers for Toxic Industrial Gasses.

Ammonia (NH3), often stored in large quantities before being used in the production of fertilizer, and sulfur dioxide (SO2), a byproduct of fossil fuel consumption, particularly the burning of coal, are highly toxic and corrosive gases that pose a significant danger to humans if accidentally released. Therefore, developing advanced materials to enable their effective capture and safe storage is highly desired. Herein, advanced benzimidazole-derived carbons (BIDCs) with an exceptional capacity for NH3 and SO2 have been designed and tested. These heteroatom-doped porous carbon adsorbents were synthesized by thermolysis of imidazolate-potassium salts affording high surface area and controlled heteroatom content to optimize for rapid NH3 and SO2 gas uptake and release under practical conditions. According to gas uptake measurements, these nitrogen-doped carbons exhibit exceptional gas adsorption capacity, with BIDC-3-800 adsorbing 21.42 mmol/g SO2 at 298 K and 1 bar, exceeding most reported porous materials and BIDC-2-700 adsorbing 14.26 mmol/g NH3 under the same conditions. The NH3 uptake of BIDC-2-700 surpassed reported activated carbons and is among the best adsorbents including metal organic frameworks (MOFs). Our synthetic method allows for control over both textural and chemical properties of the carbon and enables heteroatom functionality to be incorporated directly into the carbon framework without the need for postsynthetic modification. These materials were also tested for recyclability; all adsorbents showed almost complete retention of their initial gas uptake capacity during recyclability studies and maintained their structural integrity and their previous adsorption capacity of both NH3 and SO2, highlighting their potential for practical application.

SON drives oncogenic RNA splicing in glioblastoma by regulating PTBP1/PTBP2 switching and RBFOX2 activity.

While dysregulation of RNA splicing has been recognized as an emerging target for cancer therapy, the functional significance of RNA splicing and individual splicing factors in brain tumors is poorly understood. Here, we identify SON as a master regulator that activates PTBP1-mediated oncogenic splicing while suppressing RBFOX2-mediated non-oncogenic neuronal splicing in glioblastoma multiforme (GBM). SON is overexpressed in GBM patients and SON knockdown causes failure in intron removal from the PTBP1 transcript, resulting in PTBP1 downregulation and inhibition of its downstream oncogenic splicing. Furthermore, SON forms a complex with hnRNP A2B1 and antagonizes RBFOX2, which leads to skipping of RBFOX2-targeted cassette exons, including the PTBP2 neuronal exon. SON knockdown inhibits proliferation and clonogenicity of GBM cells in vitro and significantly suppresses tumor growth in orthotopic xenografts in vivo. Collectively, our study reveals that SON-mediated RNA splicing is a GBM vulnerability, implicating SON as a potential therapeutic target in brain tumors.

Orthoplastic management of open tibial fractures in children : a consecutive five-year series from a paediatric major trauma centre.

AIMS: Open tibial fractures are limb-threatening injuries. While limb loss is rare in children, deep infection and nonunion rates of up to 15% and 8% are reported, respectively. We manage these injuries in a similar manner to those in adults, with a combined orthoplastic approach, often involving the use of vascularised free flaps. We report the orthopaedic and plastic surgical outcomes of a consecutive series of patients over a five-year period, which includes the largest cohort of free flaps for trauma in children to date. METHODS: Data were extracted from medical records and databases for patients with an open tibial fracture aged < 16 years who presented between 1 May 2014 and 30 April 2019. Patients who were transferred from elsewhere were excluded, yielding 44 open fractures in 43 patients, with a minimum follow-up of one year. Management was reviewed from the time of injury to discharge. Primary outcome measures were the rate of deep infection, time to union, and the Modified Enneking score. RESULTS: The mean age of the patients was 9.9 years (2.8 to 15.8), and 28 were male (64%). A total of 30 fractures (68%) involved a motor vehicle collision, and 34 (77%) were classified as Gustilo Anderson (GA) grade 3B. There were 17 (50%) GA grade 3B fractures, which were treated with a definitive hexapod fixator, and 33 fractures (75%) were treated with a free flap, of which 30 (91%) were scapular/parascapular or anterolateral thigh (ALT) flaps. All fractures united at a median of 12.3 weeks (interquartile range (IQR) 9.6 to 18.1), with increasing age being significantly associated with a longer time to union (p = 0.005). There were no deep infections, one superficial wound infection, and the use of 20 fixators (20%) was associated with a pin site infection. The median Enneking score was 90% (IQR 87.5% to 95%). Three patients had a bony complication requiring further surgery. There were no flap failures, and eight patients underwent further plastic surgery. CONCLUSION: The timely and comprehensive orthoplastic care of open tibial fractures in this series of patiemts aged < 16 years resulted in 100% union and 0% deep infection, with excellent patient-reported functional outcomes. Cite this article: Bone Joint J 2021;103-B(6):1160-1167.

Screening and Purification of Natural Products from Actinomycetes that Induce a "Rounded" Morphological Phenotype in Fission Yeast.

This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a "rounded" or "small" cellular morphological phenotype. Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain, SAK950 showed that many induced a "rounded" phenotype. We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes. We show that five of the strains produced streptothricin and that 26 strains produced polyenes, including fungichromin, filipin and candicidin, the last of which was produced by 24 strains. A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S. albidoflavus whilst those that additionally produced streptothricin were related to S. enissocaesilis. A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern. The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S. pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.

SON inhibits megakaryocytic differentiation via repressing RUNX1 and the megakaryocytic gene expression program in acute megakaryoblastic leukemia.

A high incidence of acute megakaryoblastic leukemia (AMKL) in Down syndrome patients implies that chromosome 21 genes have a pivotal role in AMKL development, but the functional contribution of individual genes remains elusive. Here, we report that SON, a chromosome 21-encoded DNA- and RNA-binding protein, inhibits megakaryocytic differentiation by suppressing RUNX1 and the megakaryocytic gene expression program. As megakaryocytic progenitors differentiate, SON expression is drastically reduced, with mature megakaryocytes having the lowest levels. In contrast, AMKL cells express an aberrantly high level of SON, and knockdown of SON induced the onset of megakaryocytic differentiation in AMKL cell lines. Genome-wide transcriptome analyses revealed that SON knockdown turns on the expression of pro-megakaryocytic genes while reducing erythroid gene expression. Mechanistically, SON represses RUNX1 expression by directly binding to the proximal promoter and two enhancer regions, the known +23 kb enhancer and the novel +139 kb enhancer, at the RUNX1 locus to suppress H3K4 methylation. In addition, SON represses the expression of the AP-1 complex subunits JUN, JUNB, and FOSB which are required for late megakaryocytic gene expression. Our findings define SON as a negative regulator of RUNX1 and megakaryocytic differentiation, implicating SON overexpression in impaired differentiation during AMKL development.

Heterogeneous catalysis by ultra-small bimetallic nanoparticles surpassing homogeneous catalysis for carbon-carbon bond forming reactions.

Palladium catalyzed cross-coupling reactions represent a significant advancement in contemporary organic synthesis as these reactions are of strategic importance in the area of pharmaceutical drug discovery and development. Supported palladium-based catalysts are highly sought-after in carbon-carbon bond forming catalytic processes to ensure catalyst recovery and reuse while preventing product contamination. This paper reports the development of heterogeneous Pd-based bimetallic catalysts supported on fumed silica that have high activity and selectivity matching those of homogeneous catalysts, eliminating the catalyst's leaching and sintering and allowing efficient recycling of the catalysts. Palladium and base metal (Cu, Ni or Co) contents of less than 1.0 wt% loading are deposited on a mesoporous fumed silica support (surface area SABET = 350 m2 g-1) using strong electrostatic adsorption (SEA) yielding homogeneously alloyed nanoparticles with an average size of 1.3 nm. All bimetallic catalysts were found to be highly active toward Suzuki cross-coupling (SCC) reactions with superior activity and stability for the CuPd/SiO2 catalyst. A low CuPd/SiO2 loading (Pd: 0.3 mol%) completes the conversion of bromobenzene and phenylboronic acid to biphenyl in 30 minutes under ambient conditions in water/ethanol solvent. In contrast, monometallic Pd/SiO2 (Pd: 0.3 mol%) completes the same reaction in three hours under the same conditions. The combination of Pd with the base metals helps in retaining the Pd0 status by charge donation from the base metals to Pd, thus lowering the activation energy of the aryl halide oxidative addition step. Along with its exceptional activity, CuPd/SiO2 exhibits excellent recycling performance with a turnover frequency (TOF) of 280 000 h-1 under microwave reaction conditions at 60 °C. Our study demonstrates that SEA is an excellent synthetic strategy for depositing ultra-small Pd-based bimetallic nanoparticles on porous silica for SCC. This avenue not only provides highly active and sintering-resistant catalysts but also significantly lowers Pd contents in the catalysts without compromising catalytic activity, making the catalysts very practical for large-scale applications.

A Hybrid RNN-HMM Approach for Weakly Supervised Temporal Action Segmentation.

Action recognition has become a rapidly developing research field within the last decade. But with the increasing demand for large scale data, the need of hand annotated data for the training becomes more and more impractical. One way to avoid frame-based human annotation is the use of action order information to learn the respective action classes. In this context, we propose a hierarchical approach to address the problem of weakly supervised learning of human actions from ordered action labels by structuring recognition in a coarse-to-fine manner. Given a set of videos and an ordered list of the occurring actions, the task is to infer start and end frames of the related action classes within the video and to train the respective action classifiers without any need for hand labeled frame boundaries. We address this problem by combining a framewise RNN model with a coarse probabilistic inference. This combination allows for the temporal alignment of long sequences and thus, for an iterative training of both elements. While this system alone already generates good results, we show that the performance can be further improved by approximating the number of subactions to the characteristics of the different action classes as well as by the introduction of a regularizing length prior. The proposed system is evaluated on two benchmark datasets, the Breakfast and the Hollywood extended dataset, showing a competitive performance on various weak learning tasks such as temporal action segmentation and action alignment.

Hypoxia induces cancer cell-specific chromatin interactions and increases MALAT1 expression in breast cancer cells.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA overexpressed in various cancers that promotes cell growth and metastasis. Although hypoxia has been shown to up-regulate MALAT1, only hypoxia-inducible factors (HIFs) have been implicated in activation of the MALAT1 promoter in specific cell types and other molecular mechanisms associated with hypoxia-mediated MALAT1 up-regulation remain largely unknown. Here, we demonstrate that hypoxia induces cancer cell-specific chromatin-chromatin interactions between newly identified enhancer-like cis-regulatory elements present at the MALAT1 locus. We show that hypoxia-mediated up-regulation of MALAT1 as well as its antisense strand TALAM1 occurs in breast cancer cells, but not in nontumorigenic mammary epithelial cells. Our analyses on the MALAT1 genomic locus discovered three novel putative enhancers that are located upstream and downstream of the MALAT1 gene body. We found that parts of these putative enhancers are epigenetically modified to a more open chromatin state under hypoxia in breast cancer cells. Furthermore, our chromosome conformation capture experiment demonstrated that noncancerous cells and breast cancer cells exhibit different interaction profiles under both normoxia and hypoxia, and only breast cancer cells gain specific chromatin interactions under hypoxia. Although the HIF-2α protein can enhance the interaction between the promoter and the putative 3' enhancer, the gain of chromatin interactions associated with other upstream elements, such as putative -7 and -20 kb enhancers, were HIF-independent events. Collectively, our study demonstrates that cancer cell-specific chromatin-chromatin interactions are formed at the MALAT1 locus under hypoxia, implicating a novel mechanism of MALAT1 regulation in cancer.

Changes in ocular signs and symptoms in patients switching from bimatoprost-timolol to tafluprost-timolol eye drops: an open-label phase IV study.

OBJECTIVES: Bimatoprost-timolol (bimatoprost 0.03%-timolol 0.5% fixed-dose combination [FDC]) and tafluprost-timolol (tafluprost 0.0015%-timolol 0.5% FDC) eye drops are currently the only topical intraocular pressure (IOP)-reducing therapies available as preservative-free (PF) prostaglandin and timolol FDC. The aim of this study was to investigate changes to ocular signs and symptoms when patients with ocular hypertension (OH) or open-angle glaucoma (OAG) switched from PF or benzalkonium chloride (BAK)-preserved bimatoprost-timolol to PF tafluprost-timolol eye drops. DESIGN: This was a 12-week, open-label, phase IV study. SETTING: Sixteen centres in Finland, Germany, Italy and the UK. PARTICIPANTS: Patients with OH or OAG (IOP on medication ≤21 mm Hg), treated with PF or BAK-preserved bimatoprost-timolol for ≥4 weeks before screening, and presenting with conjunctival hyperaemia and ≥1 ocular symptom. INTERVENTIONS: Patients were switched to PF tafluprost-timolol once daily in the treated eye(s). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoints were change from screening to week 12 in conjunctival hyperaemia and worst ocular symptom. The secondary outcome measures were changes from screening in ocular signs (other than conjunctival hyperaemia) and symptoms at week 12. RESULTS: Of 123 enrolled patients, 121 were included in the intention-to-treat dataset, of which all were Caucasian and 54.5% were female; 76 patients used BAK-preserved bimatoprost-timolol and 45 used PF drops. Conjunctival hyperaemia and severity of worst ocular symptom following switch to PF tafluprost-timolol significantly reduced from screening to week 12 in all patients (p<0.001). The percentage of patients with ocular signs and symptoms was significantly reduced at week 12 compared with screening (p<0.001). IOP was not affected by the change of treatment. CONCLUSIONS: Switching from BAK-preserved or PF bimatoprost-timolol to tafluprost-timolol reduced both signs and symptoms of ocular surface disease with no clinically relevant effect on IOP. TRIAL REGISTRATION NUMBER: EudraCT2014-005273-37; Results.

SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal phenotypes.

Although genetic testing is increasingly used in clinical nephrology, a large number of patients with congenital abnormalities of the kidney and urinary tract (CAKUT) remain undiagnosed with current gene panels. Therefore, careful curation of novel genetic findings is key to improving diagnostic yields. We recently described a novel intellectual disability syndrome caused by de novo heterozygous loss-of-function mutations in the gene encoding the splicing factor SON. Here, we show that many of these patients, including two previously unreported, exhibit a wide array of kidney abnormalities. Detailed phenotyping of 14 patients with SON haploinsufficiency identified kidney anomalies in 8 patients, including horseshoe kidney, unilateral renal hypoplasia, and renal cysts. Recurrent urinary tract infections, electrolyte disturbances, and hypertension were also observed in some patients. SON knockdown in kidney cell lines leads to abnormal pre-mRNA splicing, resulting in decreased expression of several established CAKUT genes. Furthermore, these molecular events were observed in patient-derived cells with SON haploinsufficiency. Taken together, our data suggest that the wide spectrum of phenotypes in patients with a pathogenic SON mutation is a consequence of impaired pre-mRNA splicing of several CAKUT genes. We propose that genetic testing panels designed to diagnose children with a kidney phenotype should include the SON gene.

Why do patients not kneel after total knee replacement? Is neuropathic pain a contributing factor?

AIMS: Despite kneeling being an important and valued function of the knee, a proportion of patients are unable to kneel following arthroplasty. We explore the reasons for this, and assess whether neuropathic pain is a contributing factor. METHODS: In this observational study, data was collected prospectively for 134 knees. At one year follow-up, patients completed a semi-structured questionnaire, the Oxford Knee Score (OKS), and the painDETECT score. Ability to kneel was assessed by question 7 of the OKS. Change in kneeling ability was assessed using Wilcoxon signed-rank test, normal data with independent t-test, and a regression and ANOVA analysis performed to assess predictors of kneeling ability. RESULTS: 88% of patients had tried kneeling post-operatively. There was no change in kneeling ability for the whole cohort from pre- to post-operatively (p = 0.313). Patient reasons for not kneeling varied. Male gender, younger age and a reduced pain score were all significantly associated with a greater ability to kneel postoperatively. There was a trend towards an improved ability with increased flexion. Mean pain scores for all kneeling abilities lay within the nociceptive rather than neuropathic range. CONCLUSION: Kneeling ability varies greatly post-knee replacement, and is multifactorial. Greater pain is a contributing factor to the inability to kneel postoperatively, but this appears to be nociceptive rather than neuropathic in nature.

Rib fracture fixation as a tool for extubation in a resource-poor environment.

An elderly female with multiple comorbidities was involved in a pedestrian vehicle accident and sustained blunt chest trauma, arriving at a resource-poor hospital in rural South Africa. She had multiple bilateral rib fractures with a unilateral flail segment that caused her to develop respiratory failure. She was intubated and sent to the intensive care unit (ICU) for ventilation. She developed hospital and ventilator acquired pneumonia. She subsequently had hypoxic arrests on two separate occasions and two failed extubations. Despite inadequate access to provisions, this patient was taken to theatre for rib fracture fixation as an attempt to improve her lung function and get her off the ventilator. She was extubated two days after the procedure and discharged from ICU 4 days thereafter. On her follow-up, she reported that she had returned to normal daily living and tasks.