Integrated Circular Dichroism and Circularly Polarized Luminescence Measurements.

Circularly polarized luminescent (CPL) systems have a plethora of potential applications owing to their interesting excited-state properties. However, the progress in developing new chiral luminescence systems is significantly hindered by the lack of available instrumentation for the broader chemistry and materials science community to perform routine, reproducible measurements of chiral spectroscopies. In this work, we present data from an easy-to-use custom-built instrument based on a Jasco circular dichroism (CD) spectropolarimeter coupled with a CPL emission monochromator (CD/CPL hybrid system). The hybrid system measures CPL, fluorescence, CD, and absorbance on the same part of the sample without the need to move between the CD and CPL measurements. The instrument uses a xenon arc lamp as the light source, enabling a wide range of excitation wavelengths to support flexible development of new molecules and materials. Data obtained and presented for camphor, ruthenium metal complexes, the peptide gramicidin, and a DNA-ligand (4',6-diamidino-2-phenylindole, DAPI) system in this work highlight the ease of use and reproducibility of the results. The g-factors for CD and CPL obtained for the different compounds are shown to be the same for isolated transitions and some examples of how to use variations of g-factors with wavelength are demonstrated. The reliable and excellent benchmark results obtained from a custom-built commercial wavelength scanning CPL/CD hybrid instrument open up new avenues for the broader chemical and materials science community to intensify research on chiral luminescent systems.

Perioperative clinical practice recommendations for pediatric tonsillectomy: a systematic review.

PURPOSE: Tonsillectomy is one of the most common surgical procedures performed in children. Since most clinical practice guidelines (CPGs) are designed to support surgical decisions, none are specifically designed for the perioperative management of children undergoing tonsillectomy. We aimed to identify and analyze the existing CPGs with recommendations for the perioperative management of children undergoing tonsillectomy by conducting a systematic review. SOURCE: We searched Embase, MEDLINE, MEDLINE ePub Ahead of Print, and CINAHL for relevant articles published from inception to 3 August 2022. The inclusion criteria were: 1) CPG of perioperative recommendations for tonsillectomy under general anesthesia in children, 2) CPG that include at least one evidence-based recommendation, 3) peer-reviewed CPG published in English after 2000. We extracted data on baseline characteristics of each CPG and general recommendations for perioperative interventions or complications. PRINCIPAL FINDINGS: Out of five eligible CPGs, AGREE II and REX confirmed that two CPGs were high quality while only one of the two was recommended for implementation without modifications. Most of the recommendations were for pain management. Acetaminophen was the only medication recommended in all five CPG. Except for the oldest CPG, the CPG all supported of the use of nonsteroidal anti-inflammatory drugs and steroids as a pain adjunct. CONCLUSIONS: Acetaminophen, nonsteroidal anti-inflammatory drugs, and steroids are recommended in the perioperative management of pediatric tonsillectomy. Future CPG should further clarify the safe use of opioids based on severity of obstructive sleep apnea and in the context of opioid-sparing techniques, such as dexmedetomidine, high-dose dexamethasone, and gabapentinoids. STUDY REGISTRATION: PROSPERO (CRD42021253374); first submitted 18 June 2021.

RéSUMé: OBJECTIF: L'amygdalectomie est l'une des interventions chirurgicales les plus courantes pratiquées chez les enfants. Étant donné que la plupart des lignes directrices de pratique clinique sont conçues pour soutenir les décisions chirurgicales, aucune n'est spécifiquement conçue pour la prise en charge périopératoire des enfants bénéficiant d'une amygdalectomie. Notre objectif était d'identifier et d'analyser les lignes directrices de pratique clinique existantes comportant des recommandations pour la prise en charge périopératoire des enfants bénéficiant d'une amygdalectomie en réalisant une revue systématique. SOURCES: Nous avons recherché des articles pertinents dans Embase, MEDLINE, MEDLINE ePub Ahead of Print et CINAHL, publiés depuis la création de ces bases de données jusqu'au 3 août 2022. Les critères d'inclusion étaient les suivants : 1) lignes directrices de pratique clinique comportant des recommandations périopératoires pour l'amygdalectomie sous anesthésie générale chez les enfants, 2) lignes directrices de pratique clinique incluant au moins une recommandation fondée sur des données probantes, et 3) lignes directrices de pratique clinique évaluées par des pairs et publiées en anglais après 2000. Nous avons extrait des données sur les caractéristiques de base de chacune des lignes directrices de pratique clinique et des recommandations générales pour les interventions périopératoires ou les complications. CONSTATATIONS PRINCIPALES: Sur les cinq lignes directrices de pratique clinique admissibles, AGREE II et REX ont confirmé que deux lignes directrices de pratique clinique étaient de haute qualité, tandis qu'une seule des deux a été recommandée pour une mise en œuvre sans modifications. La plupart des recommandations portaient sur la prise en charge de la douleur. L'acétaminophène était le seul médicament recommandé dans les cinq lignes directrices de pratique clinique. À l'exception des lignes directrices de pratique clinique les plus anciennes, les autres ont toutes soutenu l'utilisation d'agents anti-inflammatoires non stéroïdiens et de stéroïdes comme adjuvants pour la douleur. CONCLUSION: L'acétaminophène, les agents anti-inflammatoires non stéroïdiens et les stéroïdes sont recommandés pour la prise en charge périopératoire de l'amygdalectomie pédiatrique. À l'avenir, les lignes directrices de pratique clinique devraient clarifier davantage l'utilisation sécuritaire des opioïdes en fonction de la gravité de l'apnée obstructive du sommeil et dans le contexte des techniques d'épargne des opioïdes, telles que la dexmédétomidine, la dexaméthasone à forte dose et les gabapentinoïdes. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021253374); soumise pour la première fois le 18 juin 2021.

Prophylaxis for pediatric postoperative nausea and vomiting: a scoping review of clinical trials.

PURPOSE: Postoperative nausea and vomiting (PONV) is common in pediatric patients undergoing general anesthesia, and clinicians seek prophylactic interventions to prevent its ill effects on patients as well as its ramifications on perioperative care. We sought to assess the body of evidence around prophylactic strategies, both pharmacologic and nonpharmacologic, targeting pediatric PONV. SOURCE: We searched MEDLINE, MEDLINE ePubs Ahead of Print and In-Process Citations, Embase Classic+Embase, the Cochrane Database of Systematic Reviews, Cochrane CENTRAL (via the Ovid platform), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the International Standard Randomized Controlled Trial Number Registry, from their inception to 23 September 2022. PRINCIPAL FINDINGS: Of 188 clinical trials, 157 (83%) investigated pharmacologic interventions, 25 (13%) investigated nonpharmacologic interventions, and six (3%) investigated mixed pharmacologic and nonpharmacologic interventions. The most common surgeries investigated for pediatric PONV were strabismus surgery (68 trials, 36%) and tonsillectomy or tympanoplasty (45 trials, 23%). Of four measurement tools used to assess PONV in the included trials, the most common was clinical judgement (170 trials, 90%). CONCLUSION: The majority of data in pediatric PONV prophylaxis is based on pharmacologic interventions, with a paucity of research in nonpharmacologic or mixed interventions. Assessing and documenting PONV using tools such as the Baxter Animated Retching Faces Scale or PONV numeric scoring system may help standardize pediatric PONV prophylaxis research moving forward. Furthermore, concurrently assessing pain and adverse effects associated with PONV might further inform our understanding of this complex clinical entity.

RéSUMé: OBJECTIF: Les nausées et vomissements postopératoires (NVPO) sont fréquents chez la patientèle pédiatrique bénéficiant d'une anesthésie générale, et les équipes cliniques recherchent des interventions prophylactiques pour prévenir leurs effets néfastes sur les patient·es ainsi que leurs ramifications sur les soins périopératoires. Nous avons cherché à évaluer l'ensemble des données probantes entourant les stratégies prophylactiques pharmacologiques et non pharmacologiques ciblant les NVPO pédiatriques. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, MEDLINE ePubs Ahead of Print and In-Process Citations, Embase Classic+Embase, la base de données des revues systématiques Cochrane, Cochrane CENTRAL (via la plateforme Ovid), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov, le système d'enregistrement international des essais cliniques de l'OMS et le registre international normalisé des numéros d'essais contrôlés randomisés, depuis leur création jusqu'au 23 septembre 2022. CONSTATATIONS PRINCIPALES: Sur 188 études cliniques, 157 (83 %) portaient sur des interventions pharmacologiques, 25 (13 %) sur des interventions non pharmacologiques et six (3 %) sur des interventions pharmacologiques et non pharmacologiques mixtes. Les chirurgies les plus fréquemment étudiées pour les NVPO pédiatriques étaient les chirurgies de strabisme (68 études, 36 %) et les amygdalectomies ou tympanoplasties (45 études, 23 %). Parmi les quatre outils de mesure utilisés pour évaluer les NVPO dans les études incluses, le plus fréquemment utilisé était le jugement clinique (170 études, 90 %). CONCLUSION: La majorité des données sur les prophylaxies pédiatriques pour prévenir les NVPO sont basées sur des interventions pharmacologiques, avec peu de recherche sur les interventions non pharmacologiques ou mixtes. L'évaluation et la documentation des NVPO à l'aide d'outils tels que l'échelle Baxter Animated Retching Faces Scale ou un système de notation numérique des NVPO peuvent aider à normaliser la recherche sur la prophylaxie pédiatrique des NVPO à l'avenir. De plus, l'évaluation simultanée de la douleur et des effets indésirables associés aux NVPO pourrait éclairer davantage notre compréhension de cette entité clinique complexe.

Combining microfluidic paper-based platform and metal-organic frameworks in a single device for phenolic content assessment in fruits.

A microfluidic paper-based device (µPAD) has been combined with metal-organic frameworks (MOFs) for total phenolic compounds (TPC) quantification in fruit samples for the first time. The performance of the µPAD, based upon the vertical flow approach, was enhanced in order to determine the TPC content with high accuracy in fruit samples. The method was based on the traditional Folin-Ciocalteu Index using gallic acid or oenotannin as reference phenolic compounds. This novel design and construction of the device are in agreement with the principles of Green Chemistry avoiding wax technology (lower toxicity). The analytical parameters that affect the colorimetric method (using digital imaging of the colored zone) performance were optimized including design, sample volume, and MOF amount. Then, the analytical features of the developed method were investigated such as dynamic range (1.6-30 mg L-1), limit of detection (0.5 mg L-1), and precision (RSD < 9%). Besides, the in-field analysis is achievable with a color stability up to 6 h after the loading process of the sample and storage stability for at least 15 days without performance losses (under vacuum at - 20 °C). Furthermore, the MOF ZIF-8@paper was characterized to study its composition and the successful combination. The feasibility of the proposed method was demonstrated by determining the TPC in 5 fruit samples using oenotannin as reference solute. The accuracy was validated by comparison of the data with the results obtained with the recommended protocol proposed by the International Organisation of Vine and Wine (OIV).

The Boyd approach: a valuable alternative to treating simple to complex elbow fractures and dislocations.

BACKGROUND: The Boyd approach is a single-incision posterior approach to the proximal radius and ulna based on a lateral anconeus muscle reflection and release of the lateral collateral ligamentous complex. This approach remains a lesser-used technique following early reports of proximal radioulnar synostosis and postoperative elbow instability. Although limited by small case series, recent literature does not support these early reported complications. This study presents a single surgeon's outcomes using the Boyd approach for the treatment of simple to complex elbow injuries. METHODS: Following institutional review board approval, a retrospective review of all patients with simple to complex elbow injuries treated consecutively using a Boyd approach by a shoulder and elbow surgeon was conducted from 2016 to 2020. All patients with at least 1 postoperative clinic visit were included. Data collected included patient demographics, injury description, postoperative complications, elbow range of motion, and radiographic findings including heterotopic ossification and proximal radioulnar synostosis. Categorical and continuous variables were reported using descriptive statistics. RESULTS: A total of 44 patients were included with an average age of 49 years (range 13-82 years). The most commonly treated injuries were Monteggia fracture-dislocations (32%) and terrible triad injuries (18%). Average follow-up was 8 months (range 1-24 months). Final average elbow active arc of motion was from 20° (range 0°-70°) of extension to 124° (range 75°-150°) of flexion. Final supination and pronation were 53° (range 0°-80°) and 66° (range 0°-90°), respectively. There were no cases of proximal radioulnar synostosis. Heterotopic ossification contributing to less than functional elbow range of motion occurred in 2 (5%) patients who elected conservative management. There was 1 (2%) case of early postoperative posterolateral instability due to repair failure of injured ligaments that required revision using a ligament augmentation procedure. Five (11%) patients experienced postoperative neuropathy, including 4 (9%) with ulnar neuropathy. Of these, 1 underwent ulnar nerve transposition, 2 were improving, and 1 had persistent symptoms at final follow-up. CONCLUSIONS: This is the largest case series available demonstrating the safe utilization of the Boyd approach for the treatment of simple to complex elbow injuries. Postoperative complications including synostosis and elbow instability may not be as common as previously understood.

Development of hybrid monoliths incorporating metal-organic frameworks for stir bar sorptive extraction coupled with liquid chromatography for determination of estrogen endocrine disruptors in water and human urine samples.

A novel coating based on hybrid monolith with metal-organic framework (MOF) onto conventional Teflon-coated magnetic stir bars was developed. For this purpose, the external surface of the Teflon stir bar was firstly vinylized in order to immobilize a glycidyl methacrylate (GMA)-based polymer onto the magnet. Then, an amino-modified MOF of type MIL-101 (NH2-MIL-101(Al)) was covalently attached to the GMA-based monolith. After the synthesis process, several parameters affecting extraction of target estrogens by stir bar sorptive extraction (SBSE) including pH, ionic strength, extraction time, stirring rate, desorption solvent, and desorption time were also investigated. The resulting hybrid monolith was evaluated as SBSE sorbent for extraction of three estrogens (estrone, 17ß-estradiol, estriol) and synthetic 17ß-ethinylestradiol from water and human urine samples followed by HPLC with fluorescence detection (excitation and emission wavelengths, 280 and 310 nm, respectively). Under the optimal experimental conditions, the analytical figures of the method were established, achieving satisfactory limits of detection in the range of 0.015-0.58 µg L-1, recovery results ranging from 70 to 95% with RSD less than 6%, and precision values (intra- and inter-extraction units) below 6%.

19S Proteasome Subunits as Oncogenes and Prognostic Biomarkers in FLT3-Mutated Acute Myeloid Leukemia (AML).

26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3) were recently identified as prognostic biomarkers and potential therapeutic targets in chronic myeloid leukemia (CML) and multiple solid tumors. In the present study, we analyzed the expression of 19S proteasome subunits in acute myeloid leukemia (AML) patients with mutations in the FMS-like tyrosine kinase 3 (FLT3) gene and assessed their impact on overall survival (OS). High levels of PSMD3 but not PSMD1 expression correlated with a worse OS in FLT3-mutated AML. Consistent with an oncogenic role for PSMD3 in AML, shRNA-mediated PSMD3 knockdown impaired colony formation of FLT3+ AML cell lines, which correlated with increased OS in xenograft models. While PSMD3 regulated nuclear factor-kappa B (NF-κB) transcriptional activity in CML, we did not observe similar effects in FLT3+ AML cells. Rather, proteomics analyses suggested a role for PSMD3 in neutrophil degranulation and energy metabolism. Finally, we identified additional PSMD subunits that are upregulated in AML patients with mutated versus wild-type FLT3, which correlated with worse outcomes. These findings suggest that different components of the 19S regulatory complex of the 26S proteasome can have indications for OS and may serve as prognostic biomarkers in AML and other types of cancers.

Epidemiology of Bone Fractures in the Hand in Adult Population Using the ICD-10 Classification.

PURPOSE OF THE STUDY The purpose of this study was to conduct an epidemiological study of hand fractures in adult population. MATERIAL AND METHODS A retrospective observational study in a population of 470,000 habitants was performed. Over the course of three years, all patients over 16 years of age who were diagnosed with fracture or fracture-dislocation at the level of a carpal bone, metacarpal and/or phalange were included. These fractures were classified according to the International Classification of Diseases 10th edition (ICD-10). Incidence rates, along with gender and age distribution were also studied. RESULTS 1,267 patients with a total of 1,341 hand fractures were included. They represented 29.7% of all upper limb fractures and 7.6% of all traumatological emergencies involving a bone fracture during that period. The most frequent ICD-10 group was S62.3, with the fifth metacarpal as the most often affected bone (39.7%). The most frequent location at the level of the phalanges (S62.5) was the proximal third of the proximal phalanx of the fifth radius. The global incidence rate was 99 fractures per 100,000 persons/year. No seasonal variation was observed. Only 10.2% of hand fractures received surgical treatment. DISCUSSION Several epidemiological studies have been published on fractures in the hand, but none have used the ICD-10 classification. Although the distribution of our stratified sample by age and gender was similar to those previously published, the incidence rate in our study was much lower. We may possibly extrapolate our results to the rest of the Spanish population and even to the rest of the population of southern Europe, given the scarcity of epidemiological studies on this matter in these geographical areas. CONCLUSIONS The ICD-10 classification is useful for the description and classification of hand fractures. The most often affected group is that including metacarpals of the long fingers (S62.3), being the distal level of the fifth metacarpal in young male patients the most frequent one. Most fractures are treated conservatively and in case of surgical treatment, the preferred surgical techniques include K-wire fixation, interfragmentary compression screws and plate osteosynthesis. Key words: epidemiology, incidence, fracture, fracture dislocation, carpal bones, metacarpals, finger phalanges.

Ethnic and border differences on blood cancer presentation and outcomes: A Texas population-based study.

BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

Wind from the black-hole accretion disk driving a molecular outflow in an active galaxy.

Powerful winds driven by active galactic nuclei are often thought to affect the evolution of both supermassive black holes and their host galaxies, quenching star formation and explaining the close relationship between black holes and galaxies. Recent observations of large-scale molecular outflows in ultraluminous infrared galaxies support this quasar-feedback idea, because they directly trace the gas from which stars form. Theoretical models suggest that these outflows originate as energy-conserving flows driven by fast accretion-disk winds. Proposed connections between large-scale molecular outflows and accretion-disk activity in ultraluminous galaxies were incomplete because no accretion-disk wind had been detected. Conversely, studies of powerful accretion-disk winds have until now focused only on X-ray observations of local Seyfert galaxies and a few higher-redshift quasars. Here we report observations of a powerful accretion-disk wind with a mildly relativistic velocity (a quarter that of light) in the X-ray spectrum of IRAS F11119+3257, a nearby (redshift 0.189) optically classified type 1 ultraluminous infrared galaxy hosting a powerful molecular outflow. The active galactic nucleus is responsible for about 80 per cent of the emission, with a quasar-like luminosity of 1.5 × 10(46) ergs per second. The energetics of these two types of wide-angle outflows is consistent with the energy-conserving mechanism that is the basis of the quasar feedback in active galactic nuclei that lack powerful radio jets (such jets are an alternative way to drive molecular outflows).

Equilibrium and Kinetic Study of l- and d-Valine Adsorption in Supramolecular-Templated Chiral Mesoporous Materials.

Adsorption kinetic studies are conducted to investigate the potential to use chiral mesoporous materials nanoporous guanosine monophosphate material-1 (NGM-1) and nanoporous folic acid material-1 (NFM-1) for the enantiomeric separation of l- and d-valine. A pseudo-second-order (PSO) kinetic model is applied to test the experimental adsorption equilibrium isotherms, according to both the Langmuir and Freundlich models and the characteristic parameters for each model are determined. The calcined versions of both NGM-1 and NFM-1 fit the Langmuir model with maximum sorption capacities of 0.36 and 0.26 g/g for the preferred adsorption enantiomers, d-valine and l-valine, respectively. Experimental results and the analysis of adsorption models suggest a strong adsorbate-adsorbent interaction, and the formation of a monolayer of tightly packed amino acid on the internal mesopore surface for the preferred enantiomers.

Energy metabolism and drug response in myeloid leukaemic stem cells.

Despite significant advances in the treatment of myeloid malignancies, many patients become resistant to therapy and ultimately succumb to their disease. Accumulating evidence over the past several years has suggested that the inadequacy of many leukaemia therapies results from their failure to target the leukaemic stem cell (LSC). For this reason, the LSC population currently represents the most critical target in the treatment of myeloid malignancies. However, while LSCs are ideal targets in the treatment of these diseases, they are also the most difficult population to target. This is due to both their heterogeneity within the LSC population, and also their phenotypic similarities with normal haematopoietic stem cells. This review will highlight the current landscape surrounding LSC biology in myeloid malignancies, with a focus on altered energy metabolism, and how that knowledge is being translated into clinical advances for the treatment of chronic and acute myeloid leukaemia and myelodysplastic syndromes.

Chiral Resolution using Supramolecular-Templated Mesostructured Materials.

Chiral resolution using non-functionalized mesoporous particles is demonstrated for a variety of enantiomeric pairs. This is achieved through the use of supramolecular templated silica materials prepared with guanosine monophosphate (NGM-1) and folic acid (NFM-1) which enable direct chiral transcription onto the surface of the mesopores after solvent extraction and post calcination of the template. The chiral selectivity and kinetics of the mesoporous materials are measured by circular dichroism (CD) spectroscopy on adsorbed molecules with different affinities for the pore surface. NGM-1 and NFM-1 have opposite enantiomeric selectivity for enantiomeric pairs. These results significantly increase the potential of mesoporous materials for chiral separation and enantiomeric catalysis.

Dispersed Uniform Nanoparticles from a Macroscopic Organosilica Powder.

A colloidal dispersion of uniform organosilica nanoparticles could be produced via the disassembly of the non-surfactant-templated organosilica powder nanostructured folate material (NFM-1). This unusual reaction pathway was available because the folate and silica-containing moieties in NFM-1 are held together by noncovalent interactions. No precipitation was observed from the colloidal dispersion after a week, though particle growth occurred at a solvent-dependent rate that could be described by the Lifshitz-Slyozov-Wagner equation. An organosilica film that was prepared from the colloidal dispersion adsorbed folate-binding protein from solution but adsorbed ions from a phosphate-buffered saline solution to a larger degree. To our knowledge, this is the first instance of a colloidal dispersion of organosilica nanoparticles being derived from a macroscopic material rather than from molecular precursors.

Preoperative Patient-Recorded Outcome Measures Predict Patient Discharge Location Following Unicondylar Knee Arthroplasty.

BACKGROUND: Advantages of unicondylar knee arthroplasty (UKA) over total knee arthroplasty include rapid recovery and shorter lengths of stay following surgery. Patients requiring extended postoperative care fail to recognize these benefits. Patient-reported outcome measures have proved useful in predicting outcomes following joint arthroplasty. The purpose of this study was to identify and report preoperative patient-reported outcome measures and clinical variables that predict discharge to skilled nursing facilities following UKA. METHODS: A prospective cohort of 174 patients was used to collect 36-Item Short Form scores and objective clinical data. Univariate and multivariate analysis with backward elimination were conducted to find a predictive risk model. RESULTS: The predictive model reported (78.7% concordance, receiver operating characteristic curve c-statistic 0.719, P = .0016) demonstrates that risk factors for discharge to skilled nursing facilities are: older age (odds ratio 4.18; 95% confidence interval [CI] 1.256-13.911, P = .019), bilateral UKA procedures (odds ratio 1.887; 95% CI 1.054-3.378, P = .0326) and lower patient-reported preoperative 36-Item Short Form physical function scores (odds ratio 0.968; CI 0.938-1, P = .0488). CONCLUSION: The information presented here regarding possible patient disposition following UKA could aid informed decision-making regarding patients' short-term needs following surgery and help streamline preoperative planning.

mutation3D: Cancer Gene Prediction Through Atomic Clustering of Coding Variants in the Structural Proteome.

A new algorithm and Web server, mutation3D (http://mutation3d.org), proposes driver genes in cancer by identifying clusters of amino acid substitutions within tertiary protein structures. We demonstrate the feasibility of using a 3D clustering approach to implicate proteins in cancer based on explorations of single proteins using the mutation3D Web interface. On a large scale, we show that clustering with mutation3D is able to separate functional from nonfunctional mutations by analyzing a combination of 8,869 known inherited disease mutations and 2,004 SNPs overlaid together upon the same sets of crystal structures and homology models. Further, we present a systematic analysis of whole-genome and whole-exome cancer datasets to demonstrate that mutation3D identifies many known cancer genes as well as previously underexplored target genes. The mutation3D Web interface allows users to analyze their own mutation data in a variety of popular formats and provides seamless access to explore mutation clusters derived from over 975,000 somatic mutations reported by 6,811 cancer sequencing studies. The mutation3D Web interface is freely available with all major browsers supported.

A large-scale evaluation of computational protein function prediction.

Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.

Activity Recognition for Diabetic Patients Using a Smartphone.

Diabetes is a disease that has to be managed through appropriate lifestyle. Technology can help with this, particularly when it is designed so that it does not impose an additional burden on the patient. This paper presents an approach that combines machine-learning and symbolic reasoning to recognise high-level lifestyle activities using sensor data obtained primarily from the patient's smartphone. We compare five methods for machine-learning which differ in the amount of manually labelled data by the user, to investigate the trade-off between the labelling effort and recognition accuracy. In an evaluation on real-life data, the highest accuracy of 83.4 % was achieved by the MCAT method, which is capable of gradually adapting to each user.

Non-absorbable mesoporous silica for the development of protein sequestration therapies.

While our understanding of the molecular events leading to disease onset and progression have increased exponentially, our capacity to therapeutically intervene in these events with new chemical diversity has clearly fallen short of that pace. In the quest to readdress this situation, the drug discovery sector is slowly but increasingly exploring sources of alternative chemical matter, such as the ones provided by material science and nanotechnology. While new functional nano-sized materials hold great promise for the future, our lack of understanding of the long term safety implications associated with systemic exposure as well as the unclear regulatory path ahead hamper their present impact in drug development. Paradoxically, the exploitation of novel, functionally active micron-sized, synthetic, non-absorbable chemical matter, for the treatment or prevention of a number of epidemiologically significant conditions remains clearly underexplored. A combination of pre-existing evidence and future potential indicates that micron-sized mesoporous silica materials could be an untapped source of new drug candidates. These are free from both the dreaded high attrition associated with small molecule drug discovery and the uncertainties of nano-size technologies. This, together with the coming of age of synthetic methodologies to control particle size and shape; pore size and geometry; surface chemistry, bioconjugation and formulation, open up exciting possibilities to exploit this novel chemistry-biology therapeutic interface.

GOssTo: a stand-alone application and a web tool for calculating semantic similarities on the Gene Ontology.

SUMMARY: We present GOssTo, the Gene Ontology semantic similarity Tool, a user-friendly software system for calculating semantic similarities between gene products according to the Gene Ontology. GOssTo is bundled with six semantic similarity measures, including both term- and graph-based measures, and has extension capabilities to allow the user to add new similarities. Importantly, for any measure, GOssTo can also calculate the Random Walk Contribution that has been shown to greatly improve the accuracy of similarity measures. GOssTo is very fast, easy to use, and it allows the calculation of similarities on a genomic scale in a few minutes on a regular desktop machine. CONTACT: alberto@cs.rhul.ac.uk AVAILABILITY: GOssTo is available both as a stand-alone application running on GNU/Linux, Windows and MacOS from www.paccanarolab.org/gossto and as a web application from www.paccanarolab.org/gosstoweb. The stand-alone application features a simple and concise command line interface for easy integration into high-throughput data processing pipelines.