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The digital clinical trial is fast emerging as a pragmatic trial that can improve a trial’s design including recruitment and retention, data collection and analytics. To that end, digital platforms such as electronic health records or wearable technologies that enable passive data collection can be leveraged, alleviating burden from the participant and study coordinator. However, there are challenges. For example, many of these data sources not originally intended for research may be noisier than traditionally-obtained measures. Further, the secure flow of passively collected data and their integration for analysis is non-trivial. The Apple Heart Study was a prospective, single-arm, site-less digital trial designed to evaluate the ability of an app to detect atrial fibrillation. The study was designed with pragmatic features, such as an app for enrollment, a wearable device (the Apple Watch) for data collection, and electronic surveys for participant-reported outcomes that enabled a high volume of patient enrollment and accompanying data. These elements led to challenges including identifying the number of unique participants, maintaining participant-level linkage of multiple complex data streams, and participant adherence and engagement. Novel solutions were derived that inform future designs with an emphasis on data management. We build upon the excellent framework of the Clinical Trials Transformation Initiative to provide a comprehensive set of guidelines for data management of the digital clinical trial that include an increased role of collaborative data scientists in the design and conduct of the modern digital trial.

Objectives/Context: To evaluate the relationship between severity of neurogenic bowel dysfunction (NBD) and functional status, depression, and quality of life in individuals with spinal cord injury (SCI) and to determine the factors associated with developing moderate-to-severe NBD. Design: Cross-sectional study. Setting: University hospital rehabilitation outpatient clinic. Participants: Individuals with traumatic SCI, at least one year post-injury (N = 92). Interventions: Not applicable. Main Outcome Measures: Neurogenic Bowel Dysfunction Score, Functional Independence Measure (FIM), Beck Depression Inventory (BDI), and Short Form-36 (SF-36). Results: In the current sample, we found that half of the individuals with SCI had moderate-to-severe NBD. Individuals with moderate and severe NBD had lower motor FIM (P = 0.008 and P = 0.006, respectively) and SF-36 physical functioning (PF) scale (P = 0.020 and P = 0.031, respectively) scores than individuals with very minor NBD. There was no difference in the BDI scores among individuals with different levels of NBD. Individuals with American Spinal Injury Association Impairment Scale (AIS) A injuries were more likely to develop moderate-to-severe NBD than those with AIS C (odds ratio (OR) = 6.52; 95% confidence interval (CI) 1.13–37.79; P = 0.005) or AIS D (OR = 17.19; 95% CI 3.61–81.82; p

Türe, Sedat (Bilecik, Author) Gurbanov, Rafıg (Bilecik, Author) The reactions of hexachlorocyclotriphosphazatriene, N3P3Cl6 (1) with 2-mercaptoethanol, 2-HS-CH2-CH2-OH (2), in (1:1, 1:2 and 1:3) mole ratios, in excess of NaH, in THF and diethylether solutions yield a total of 6 novel products: one mono spiro, N3P3Cl4[O-CH2-CH2-S] (3); one mono-substituted open chain, N3P3Cl5[S-CH2-CH2-OH] (4); one dispiro, N3P3Cl2[O-CH2-CH2-S](2) (5); one tri-substituted open chain, N3P3Cl3[S-CH2-CH2-OH](3) (6); one tris-spiro, N3P3[O-CH2-CH2-S](3) (7) and one disubstituted open chain, N3P3Cl4[S-CH2-CH2-OH](2) (8) derivatives. The spiro products (3, 5 and 7) are formed as the major products in this system and all of the synthesized compounds are found to be stable at room temperature. The structures of the derived compounds were elucidated by elemental analysis, TLC-MS, P-31 and H-1 NMR spectral data. For evaluation of melting behavior of derivatives (6) and (7), thermal transition peaks and their corresponding enthalpies were determined via DSC technique. Bilecik Şeyh Edebali Üniversitesi Bilimsel Araştırma Projesi - BAP - 2016-01.BŞEÜ.04-02. Bilecik Seyh Edebali University Scientific Research Project - BAP - 2016-01.BŞEÜ.04-02. WOS:000452036700009 Q3 Q4

Reactions of non-gem-hexanedioxytetrachlorocyclotriphosphazene (1) with monofunctional nucleophilic reagents, 2-(2-hydroxyethyl)thiophene (2), benzyl alcohol (3) and 1,1,3,3-tetramethylguanidine (4) were investigated. The reactions, using an excess of NaH, in THF solutions, under refluxing conditions and with 1:2 mole ratios allow the synthesis of the following novel cyclotriphosphazene derivatives: 2,4-dichloro-2,4-(hexane-1,6-dioxy)-6,6-[2-(2-ethoxy)hiophene]-cyclotriphosphazatriene, N3P3Cl2[O(CH2)6O-(C6H8OS)2] (5); 2,4-(hexane-1,6-dioxy)-2,4,6,6-[2-(2-ethoxy) thiophene]-cyclotriphosphazatriene, N3P3[O(CH2)6O-(C6H8OS)4] (6); 2,4-dichloro-2,4-(hexane-1,6-dioxy)-6,6-(methoxybenzene)-cyclotriphosphazatriene, N3P3Cl2[O(CH2)6O-(C6H5CH2O)2] (7); 2,4-(hexane-1,6-dioxy)-2,4,6,6-(methoxybenzene)-cyclotriphosphazatriene, N3P3[O(CH2)6O-(C6H5CH2O)4] (8); and 2,4-dichloro-2,4-(hexane-1,6-dioxy)-6,6-(1,1,3,3-tetramethyguanidine)-cyclotriphosphazatriene, N3P3Cl2[O(CH2)6O-HN-CN2(CH3)4] (9). The structures of the synthesized compounds (5–9) have been characterized by elemental analysis, TLC-MS, 1H, 13C and 31P {+1H} and {−1H} NMR spectral data.

The reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (1) with 1,1,3,3-tetramethyl-guanidine (2) in (1:1:2, 1:2:4 and 1:3:6) stoichiometries in THF and dichloromethane solutions under reflux yield a total of 4 novel products: three non-geminal derivatives, N3P3Cl4[NCN2(CH3)4]2 (3), N3P3Cl3[NCN2(CH3)4]3 (4) and N3P3Cl2[NCN2(CH3)4]4 (5); and one hexa-substituted product, N3P3[NCN2(CH3)4]6 (6). The structures of 3-6 have been determined mainly by elemental analysis, MS, 31P and 1H NMR spectral data. Furthermore, thermal characteristics of the synthesized compounds 4 and 6 were evaluated using Differential Scanning Calorimetric (DSC) measurements. NMR spectroscopic data, product types and relative yields are compared with those of the previously investigated derivatives of N3P3Cl6 (1) with mono and difunctional reagents.

Statistical methods such as Poisson distribution, negative binomial regression (NB), and zero inflated negative binomial regression (ZINB) have generally been used in road safety studies to establish the complex relationships between variables. Over the last few years, the artificial neural networks (ANN) model has also been used. The ANN model does not have any prior limitations such as the equality condition of mean and variance observed in Poisson regression. However, though the ANN model has been used in the analysis of different accident types, to the best of our knowledge, no study has used the ANN model for establishing this relationship with truck accident data on divided multilane interurban roads. In this study, the road sections D750/07–D750/15 in Ankara–Aksaray–Eregli, Turkey, were considered and truck accident data from 2008 to 2011 were analyzed using NB and ANN. The analysis show that the ANN model has lower errors and higher R2 values than NB and performs slightly better than NB fo...

Reactions of hexachlorocyclotriphosphazene N3P3Cl6 (1) with 1,4-butane-(2) and 1,6-hexane-diols (3) in (1:1:2, 1:2:4, and 1:3:6) stoichiometries in THF solution at room temperature (r.t.) and under...

Black scholars who reside in the United States balance their teaching, research responsibility, and lived experience with the urgent need to address the racial inequality and violence that has characterized Black life. The authors of this article explore police-involved homicides of unarmed Black males through the unique lens of Black scholars. Embedded in an ecological perspective, the authors address three critical questions: (1) From the viewpoint of the Black scholar, what was the impact of the recent events? (2) To what extent have the recent events influenced pedagogical and community work by Black scholars? and (3) In light of the recent events, what can be done to improve policies and strengthen your academic discipline? The insights offered by eight multidisciplinary authors offer promising alternatives to current public policy, training, and general community practice.

The reactions of octachlorocyclotetraphosphazatetraene, N4P4Cl8 (1) with difunctional aliphatic reagent, HO-(CH2)5-OH (3) have aroused a good deal of attention, and four types of products have been...

Clostridium difficile infection (CDI) is of concern in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Metronidazole and vancomycin have been considered as a first-line therapy fo...

The reactions of octochlorocyclotetraphosphazatetraene, N4P4Cl4 (1) with difunctional bis(2-hydroxyethyl) ether gave the following isolated and characterized products: one mono-spiro, N4P4Cl6[(OCH2...

Objective: To create a user-operated pure-tone audiometry method based on the method of maximum likelihood (MML) and the two-alternative forced-choice (2AFC) paradigm with high test-retest reliability without the need of an external operator and with minimal influence of subjects' fluctuating response criteria. User-operated audiometry was developed as an alternative to traditional audiometry for research purposes among musicians. Design: Test-retest reliability of the user-operated audiometry system was evaluated and the user-operated audiometry system was compared with traditional audiometry. Study sample: Test-retest reliability of user-operated 2AFC audiometry was tested with 38 naïve listeners. User-operated 2AFC audiometry was compared to traditional audiometry in 41 subjects. Results: The repeatability of user-operated 2AFC audiometry was comparable to traditional audiometry with standard deviation of differences from 3.9 dB to 5.2 dB in the frequency range of 250-8000 Hz. User-operated 2AFC audiometry gave thresholds 1-2 dB lower at most frequencies compared to traditional audiometry. Conclusions: User-operated 2AFC audiometry does not require specific operating skills and the repeatability is acceptable and similar to traditional audiometry. User operated 2AFC audiometry is a reliable alternative to traditional audiometry.

The reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (1), with 2,2-dimethylpropane-1,3-diol (2), and bis(2-hydroxyethyl) ether (3) have been previously reported. Although both reactions gave the expected spiro, ansa, and bridged type products, open-chain and triply bridged derivatives from both systems and singly bridged derivatives from 2,2-dimethylpropane-1,3-diol (2) were not isolated, and doubly bridged compounds were only detected in trace amounts in both systems. However, in a subsequent reinvestigation in tetrahydrofuran (THF) solution, the reaction of 1 with the diols 2 and 3 gave the open chain compounds N3P3Cl5[O(CH2)2CMe2OH] (4) and N3P3Cl5[(OCH2CH2)2OH] (5), the singly bridged compound N3P3Cl5[(OCH2)2-CMe2]N3P3Cl5 (6), the doubly bridged compounds N3P3Cl4[(OCH2)2CMe2]2N3P3Cl4 (8) and N3P3Cl4[(OCH2CH2)2O]2N3P3Cl4 (9), and the triply bridged compounds N3P3Cl3[(OCH2)2-CMe2]3N3P3Cl3 (10) and N3P3Cl3[(OCH2CH2)2O]3N3P3Cl3 (11). The doubly bridged derivatives were also isolated in better ...

From the reactions of hexachlorocyclotriphosphazatriene, N3P3Cl6 (1) with pentane-1,5-diol (2) in dichloromethane solution, the following derivatives have been isolated: 2,2-spiro(1′,5′-pentanedioxy)-4,4,6,6-tetrachlorocyclotriphosphazatriene, N3P3Cl4[O(CH2)5O] (3); its ansa isomer, 1,3-ansa(1′,5′-pentanedioxy)-1,3,5,5-tetrachlorocyclotriphosphazatriene, (4); bis spiro(1′,5′-pentanedioxy)-6,6-dichlorocyclotriphosphazatriene, N3P3Cl2[O(CH2)5O]2 (5); its spiro-ansa isomer, (1′,5′-pentanedioxy)-1,3-dichlorocyclotriphosphazatriene (6); as well as the bino(1,5-pentanedioxy)-di-(pentachlorocyclotriphosphazatriene), N3P3Cl5 [O(CH2)5O]N3P3Cl5 (7), and tri-bino(1,5-pentanedioxy)-di (trichlorocyclotriphosphazatriene), N3P3Cl3[O(CH2)5O]3N3P3Cl3, (8) derivatives. Their structures were established by MS and NMR with the use of 1H, 13C, and 31P spectroscopy. Product types and relative yields are compared with those of the previously investigated diol derivatives. The yield of the mono-ansa product (25%) obtain...

Objective: Investigate genetic causes of HI among the Inuit populations in the Arctic with a high prevalence of hearing impairment (HI). Design: A cross-sectional survey with population-based controls. Study sample: Forty-five patients, with sensorineural or mixed HI and an available blood sample for GJB2 sequencing from DNA, were selected from 166 East Greenlanders by specialist audiology examination, including pure-tone air and bone conduction audiometry from 125 Hz to 8000 Hz. Controls were 108 East- and 109 West-Greenlanders. Results: Forty-five patients with HI were included, 24 males and 21 females. Median age was 35 years (range: 5-76). The c.35delG allele frequency was 3.3%. One patient, homozygous for the c.35delG GJB2 mutation, had bilateral congenital profound HI. Another with mixed HI was heterozygous for the same mutation. Three were heterozygous for the p.V27I variant and one was heterozygous for the p.V153I variant. The frequency of the c.35delG mutation in the controls varied between 0.5% in West Greenland to 2.3% in East Greenland. Conclusion: The c. 35delG GJB2 mutation occurs in Greenland with low frequency. We conclude the main causes behind the prevalence of HI in this population are chronic otitis media, noise traumas, and/or unidentified genetic causes.

This message was delivered at the opening dedication ceremony of Malcolm X Liberation University (an independent black university) in Durham, North Carolina in October, 1969. At that time, Stokely ...

Monoclonal antibodies catalyzing lysis of 4-nitrophenyl esters have been created using a phosphonate as hapten in the immunization. Among 960 hybridomas screened, 3 were found to produce antibodies catalyzing hydrolysis of 4-nitrophenyl butanoate (1). Two of the antibodies accelerate the reaction by factors of 1.3 × 104 and 1.1 × 104, respectively, while the third antibody is significantly less effective. The two catalytically most effective antibodies also catalyze perhydrolysis of 1, i.e., lysis with hydrogen peroxide, to generate peroxybutanoic acid. Perhydrolysis was found to be the predominant reaction even in dilute solutions of hydrogen peroxide. Both antibodies also catalyze hydrolysis of both 4-nitrophenyl hexanoate and decanoate, but do not catalyze hydrolysis of 4-nitrophenyl acetate. The antibodies are more selective with respect to the aromatic part of the substrate as they do not catalyze hydrolysis of 2-nitrophenyl butanoate or 4-sulfophenyl nonanoate. Furthermore, neither of the antibodies...

In the development of an efficient synthesis of 1-O-decanoyl-2,3,4,6-tetra-O-acetyl-β-D-glucose (β-2) several lipase-based approaches have been explored. Among five immobilized Upases tested, the lipase from Candida antarctica proved particularly efficient for catalyzing selective hydrolysis in the 1-position of 1,2,3,4,6-penta-O-acetyl-β-D-glucose (β-1). Using triethylamine as catalyst, the hydrolysis product 2,3,4,6-tetra-O-acetyl-D-glucose (3) can be esterified with decanoyl chloride to form β-2 selectively, thereby providing an efficient chemo-enzymatic synthesis starting from readily available raw materials. Attempts to produce β-2 from β-1 by lipase-catalyzed interesterification or to esterify 3 with decanoic acid using a lipase as catalyst were unsuccessful. The latter finding was explained by the hemiacetal OH group of glucose being unable to act as nucleophile in the lysis of the lipase acyl-enzyme intermediate. Furthermore, β-2 was found to bee a too bulky substrate to fit into the active site o...

The problem of identification and construction of optimal designs for comparing several test treatments with a control treatment is studied. Two-way heterogeneity in the experimental units is considered under the usual additive model. A general class of designs—named balanced treatment row-column designs—appears to be natural candidates for the A-optimality criterion. Catalogs of A-optimal balanced treatment row-column designs have been prepared and tabulated for a practical range of parameter values. The use of the catalogs is explained with examples.

The ability of hydrolases to catalyze perhydrolysis, i.e. lysis of acyl substrates with hydrogen peroxide to form peroxycarboxylic acids, has been investigated. Lipases, esterases and cholinesterases were found to catalyze perhydrolysis but the preference of the enzymes for hydrogen peroxide relative to water as nucleophile was only 10–100 fold, even in the best cases. Hence, perhydrolysis proceeds with a very low efficiency in aqueous systems. Furthermore, all lipases, esterases and cholinesterases tested degrade peroxycarboxylic acids to the corresponding carboxylic acid and hydrogen peroxide. This reaction is most pronounced in the case of lipases while less so for cholinesterases. Consequently, cholinesterases are superior to the other hydrolases studied in catalyzing net formation of peracids in aqueous systems. In organic solvents, immobilized lipases efficiently catalyze formation of peracids from either triglycerides or the parent carboxylic acid. Proteases and phospholipase A-2 were found to neit...

The reactions of hexachlorocyclotriphosphazatriene with bis(2-hydroxyethy1)ether yield eight products: three spiro-derivatives. N3P3Cl4[(OCH2CH2)2O], N3P3Cl2[(OCH2 CH2)2O]2, N3P3[(OCH2CH2)2O]3, an ansa, N3P3Cl4[(OCH2 CH2)2O]2, and a spiro-ansa product N3P3Cl2[(OCH2CH2)2O]2, as well as single (N3P3Cl5)2((OCH2CH2)2O] and double-bridged derivatives, (N3P3Cl4)2[(OCH2CH2)2O]2. A hydrolysis product, N3P3Cl4[O(CH2)2O(CH2)2OH]ON3P3Cl5, was also isolated. The 1H, 31P and 13C n.m.r. spectra are reported.

The reactions of hexachlorocyclotriphosphazatriene, N3 P3 CI6, with 2, 2-dimethylpropane-1, 3-diol yield monospiro-, N3 P3 Cl4 [(OCH2)2 CMe2, dispiro-, N3 P3 Cl4((OCH2)2CMe2|2, and trispiroderivatives, N3 P3 ((OCH2)2, CMe2]3. An ansa, N3 P3 CI4 [(OCH2)2 CMe2]2 and a spiro-ansa, N3 P3 Cl2- ((OCH2), CMe2,]2 and a doubly-bridged compound, (N3 P3 Cl4,)2[(OCH2)]2 were also isolated. Product types and relative yields were compared with those arising from propane-1, 3-diol. The yields of ansa products from the reactions of the dimethyl diol seem to be considerably enhanced relative to those of its unmethylated analogue. 31P and 1H n.m.r. spectra are reported.