Machine learning and statistical physics modeling of tetracycline adsorption using activated carbon derived from Cynometra ramiflora fruit biomass.

The current investigation reports the usage of adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network (ANN), the two recognized machine learning techniques in modelling tetracycline (TC) adsorption onto Cynometra ramiflora fruit biomass derived activated carbon (AC). Many characterization methods utilized, confirmed the porous structure of synthesized AC. ANN and ANFIS models utilized pH, dose, initial TC concentration, mixing speed, time duration, and temperature as input parameters, whereas TC removal percentage was designated as the output parameter. The optimized configuration for the ANN model was determined as 6-8-1, while the ANFIS model employed trimf input and linear output membership functions. The obtained results showed a strong correlation, indicated by high R2 values (ANNR2: 0.9939 & ANFISR2: 0.9906) and low RMSE values (ANNRMSE: 0.0393 & ANFISRMSE: 0.0503). Apart from traditional isotherms, the dataset was fitted to statistical physics models wherein, the double-layer with a single energy satisfactorily explained the physisorption mechanism of TC adsorption. The sorption energy was 21.06 kJ/mol, and the number of TC moieties bound per site (n) was found to be 0.42, conclusive of parallel binding of TC molecules to the adsorbent surface. The adsorption capacity at saturation (Qsat) was estimated to be 466.86 mg/g - appreciably more than previously reported values. These findings collectively demonstrate that the AC derived from C. ramiflora fruit holds great potential for efficient removal of TC from a given system, and machine learning approaches can effectively model the adsorption processes.

Deciphering the role of Saliva in COVID 19: A global cross-sectional study on the knowledge, awareness and perception among dentists.

OBJECTIVES: The global pandemic outbreak of the coronavirus has instilled the quest amongst researchers on the expedited need for the early detection of viral load. Saliva is a complex oral biological fluid which not only causes the disease transmission but can be an effective alternative sample for detection of SARS-CoV2. This provides an ideal opportunity for dentists to be the frontline healthcare professionals who can collect the salivary samples; however the awareness of this amongst dentists is uncertain. Hence the aim of this survey was to evaluate the knowledge, perception and awareness of the role of saliva in detecting the SARS-CoV2 among dentists worldwide. METHODS: The online questionnaire comprising of 19 questions was shared to 1100 dentists worldwide and a total of 720 responses was collected. The data was tabulated, statistically analysed using the non- parametric Kruskal-Wallis test (p < 0.05). Based on the principal component analysis, 4 components (knowledge about virus transmission, perception about SARS-CoV2 virus, awareness on the sample collection and knowledge about prevention of the virus) were obtained which was compared with the 3 independent variables (years of clinical experience, occupation and region). RESULTS: A statistically significant difference was observed in the awareness quotient amongst the dentists with 0-5 years and greater than 20 years of clinical experience. In terms of the occupation, a significant difference was noted when comparing the postgraduate students to practitioners knowledge about the virus transmission. A highly significant difference was seen on comparing academicians and postgraduate students and also between academicians and practitioners. No significant difference was evidenced amongst the different regions, however the mean score was in the range of 3-3.44. CONCLUSION: This survey highlights the deficiency in the knowledge, perception and awareness among dentists worldwide.

Decreased Brain Ventricular Volume in Psychiatric Inpatients with Serotonin Reuptake Inhibitor Treatment.

Background: Brain ventricles have been reported to be enlarged in several neuropsychiatric disorders and in aging. Whether human cerebral ventricular volume can decrease over time with psychiatric treatment is not well-studied. The aim of this study was to examine whether inpatients taking serotonin reuptake inhibitors (SRI) exhibited reductions in cerebral ventricular volume. Methods: Psychiatric inpatients, diagnosed mainly with depression, substance use, anxiety, and personality disorders, underwent two imaging sessions (Time 1 and Time 2, approximately 4 weeks apart). FreeSurfer was used to quantify volumetric features of the brain, and ANOVA was used to analyze ventricular volume differences between Time 1 and Time 2. Inpatients' brain ventricle volumes were normalized by dividing by estimated total intracranial volume (eTIV). Clinical features such as depression and anxiety levels were collected at Time 1, Time 1.5 (approximately 2 weeks apart), and Time 2. Results: Inpatients consistently taking SRIs (SRI + , n = 44) showed statistically significant reductions of brain ventricular volumes particularly for their left and right lateral ventricular volumes. Reductions in their third ventricular volume were close to significance (p = .068). The inpatients that did not take SRIs (SRI-, n = 25) showed no statistically significant changes in brain ventricular volumes. The SRI + group also exhibited similar brain structural features to the healthy control group based on the 90% confidence interval comparsions on brain ventricular volume parameters, whereas the SRI- group still exhibited relatively enlarged brain ventricular volumes after treatment. Conclusions: SRI treatment was associated with decreased brain ventricle volume over treatment.

Efficient catalytic activity of BiVO4 nanostructures by crystal facet regulation for environmental remediation.

Controlled growth of BiVO4 nanostructures along (121) and (040) crystal facets plays a crucial role in enhancing their catalytic performance. In this regard, the visible light active photocatalyst BiVO4 was synthesized concerning the effect of pH and surfactants by hydrothermal method. The morphology and size of BiVO4 are strongly dependent on the concentration of H+ and Bi3+ in the reaction system while varying the pH. Further, the significant role of cationic surfactant for obtaining the morphology of the spherical nanoparticles of BiVO4 powders with size 55 nm was analyzed. Adsorption behavior of as-synthesized samples was investigated through Langmuir isotherm model. The catalytic performance of BiVO4 photocatalyst with the degradation efficiency of 98.79% and 15.58% over the methylene blue (MB) and methyl orange (MO) dyes were noticed within 60 min of light irradiation respectively. The enhanced and declined catalytic activity was well correlated with the surface charge of BiVO4 photocatalyst towards the MB and MO dyes respectively. Further, the photocatalytic activity of mixed anionic and cationic dyes was performed. The degradation pathway of MB dye was analyzed by LC-MS for the identification of intermediate products. From the obtained results, the proposed possible photocatalytic mechanism reported.

Understanding umbilical venous catheter insertion practices through a prospective multicenter observational study.

OBJECTIVE: To understand practices of umbilical venous catheter (UVC) insertion in tertiary level neonatal intensive care units (NICU) and investigate the outcomes of subsequent attempts following a failed initial attempt. STUDY DESIGN: Prospective, multi-center observational study of UVC insertions at tertiary level NICUs between March 2019 and January 2020. RESULTS: Of the 101 UVCs inserted at 4 centers, seventy-two (71%) were central at the first attempt and 50% were central at subsequent attempts. Patients with at least 1 failed attempt at insertion were less likely to have a centrally placed UVC (p = .009). Manipulations were less likely to be required when UVC was centrally placed during the first attempt. Maneuvers such as posterior liver mobilization used during insertion were likely to be associated with successful central placement of UVC (p = .0243). The time to complete the procedure was significantly less when the UVC was central at the first attempt (34.2 ± 20.2 vs 46.9 ± 33.8) (p = .0292). Gestational age, birth weight, and age of the baby at the insertion of the UVC, experience of the provider, and type of catheter were comparable among groups. The Shukla formula was most commonly used by providers to measure the depth of UVC placement. CONCLUSION: Repetitive attempts and manipulations were less likely to be beneficial in the successful central placement of UVC in neonates. Additionally, repetitive attempts at insertion prolonged the overall duration of the procedure.

Enhanced photocatalytic and photodynamic activity of chitosan and garlic loaded CdO-TiO2 hybrid bionanomaterials.

Herein, the work addresses the synthesis of biomaterials (chitosan and garlic) loaded CdO-TiO2 hybrid nanocomposites for photocatalytic water treatment and photodynamic cancer therapeutic applications that were reported the first time. CdO-TiO2 (CT) nanocomposites were synthesized and loaded with the biomaterials such as chitosan and garlic by simple sol-gel method. The nanomaterials were characterized and the photodegradation of three model pollutants, Methylene blue (MB), Methyl orange (MO) and Rhodamine B (Rh-B) was opted to investigate the efficiency of the synthesized photocatalyst under the solar light. From the results, the garlic-loaded CdO-TiO2 (AS-CT) hybrid nanocomposites exhibit a superior photocatalytic activity than the chitosan-loaded CdO-TiO2 (CS-CT) and CdO-TiO2 (CT) nanocomposites under the irradiation of solar light. Additionally, the cell viability of the synthesized nanocomposites was carried out in HeLa cell lines under different concentrations, light doses and incubation periods using an LED light source. Compared to the CS-CT and CT nanocomposites, an efficient photodynamic activity was achieved in the case of AS-CT hybrid nanocomposites. Actually, the end-use properties required for both processes in AS-CT nanocomposites appear similar due to the presence of organo sulphurus compounds.

Crystal structure and Hirshfeld surface analysis of a pyrrolo-thia-zine complex.

In the title compound, diethyl 2,2-dioxo-4-(thio-phen-2-yl)-1-[(thio-phen-2-yl)meth-yl]-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate, C22H28NO6S3, the pyrrolo ring is in an envelope conformation while the thia-zine ring adopts a near chair conformation. The dihedral angles between the thia-zine ring and the methyl-thienyl, thienyl and pyrrolo rings are 64.0 (2), 87.92 (7) and 5.6 (2)°, respectively. In the crystal, the mol-ecules are linked by weak C-H⋯O hydrogen bonds. A Hirshfeld surface analysis was performed to investigate the inter-molecular inter-actions. Disorder of the methyl-thienyl group with site occupancies of 0. 792 (3) and 0.208 (3) is observed.

Prospective cohort study of regenerative potential of non vital immature permanent maxillary central incisors using platelet rich fibrin scaffold.

Regenerative endodontic procedures have gained momentum as a treatment modality of young immature permanent teeth. Literature reports reveal that platelet-rich fibrin (PRF) stimulates growth factors and induces regeneration. This study was undertaken to assess the regenerative potential of non-vital immature permanent maxillary central incisors using PRF with a follow-up for 2 yrs. 19 patients in the age group of 9-25 yrs with immature, non-vital permanent maxillary central incisors (n = 23) with/without signs and/or symptoms of periapical pathosis and open apex were included in this study. In the first appointment, access opening, canal disinfection and triple antibiotic paste placement were done. In the subsequent visit, PRF was prepared and placed inside the canal. Access was sealed with Mineral trioxide aggregate plug and composite. The patient was reviewed up to 24 mths. The mean difference was statistically analyzed using Friedman test followed by Dunn post hoc test and adjusted by Bonferroni correction (p < 0.05). As per AAE guidelines, the primary and secondary goals were achieved. A significant (p < 0.001) gradual increase in the root length, thickness of dentinal walls and decrease in apical diameter were observed. Within the limitations of this study, PRF placement was clinically and radiographically effective in inducing regeneration of non-vital immature permanent teeth.

Differential Activation and Functional Plasticity of Multimodal Areas Associated with Acquired Musical Skill.

Training of a musical skill is known to produce a distributed neural representation of the ability to perceive music and perform musical tasks. In the present study we tested the hypothesis that the audiovisual perception of music involves a wider activation of multimodal sensory and sensorimotor structures in the brain, including those containing mirror neurons. We mapped the activation of brain areas during passive listening and viewing of the first 40 s of "Ode to Joy" being played on the piano by an expert pianist. To do this we performed brain functional magnetic resonance imaging during the presentation of 6 different stimulus contrasts pertaining to that musical melody in a pseudo-randomized order. Group data analysis in musically trained and untrained adults showed robust activation in broadly distributed occipitotemporal, parietal and frontal areas in trained subjects and much restricted activation in untrained subjects. A visual stimulus contrast focusing on the visual motion percept of moving fingers on piano keys revealed selective bilateral activation of a locus corresponding to the V5/MT area, which was significantly more pronounced in trained subjects and showed partial linear dependence on the duration of training on the left side. Quantitative analysis of individual brain volumes confirmed a significantly greater and wider spread of activation in trained compared to untrained subjects. These findings support the view that audiovisual perception of music and musical gestures in trained musicians involves an expanded and widely distributed neural representation formed due to experience-dependent plasticity.

Crystal structure and mol-ecular Hirshfeld surface analysis of acenaphthene derivatives obeying the chlorine-methyl exchange rule.

Instances of crystal structures that remain isomorphous in spite of some minor changes in their respective mol-ecules, such as change in a substituent atom/group, can provide insights into the factors that govern crystal packing. In this context, an accurate description of the crystal structures of an isomorphous pair that differ from each other only by a chlorine-methyl substituent, viz. 5''-(2-chloro-benzyl-idene)-4'-(2-chloro-phen-yl)-1'-methyl-dispiro-[acenaphthene-1,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, C34H28Cl2N2O2, (I), and its analogue 1'-methyl-5''-(2-methyl-benzyl-idene)-4'-(2-methyl-phen-yl)di-spiro-[acenaphthene-1,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, C36H34N2O2, (II), is presented. While there are two C-H⋯O weak inter-molecular inter-actions present in both (I) and (II), the change of substituent from chlorine to methyl has given rise to an additional weak C-H⋯O inter-molecular inter-action that is relatively stronger than the other two. However, the presence of the stronger C-H⋯O inter-action in (II) has not disrupted the validity of the chloro-methyl exchange rule. Details of the crystal structures and Hirshfeld analyses of the two compounds are presented.

Preparation and characterization of core-shell type Ag@SiO2 nanoparticles for photodynamic cancer therapy.

With recent scientific developments, Photodynamic therapy (PDT) offers the promisie to become incorporated into the mainstream of cancer therapy. Noble metal based nano-PDT is increasing due to its advantages in the field of biomedicine. In this study, noble metal based Ag@SiO2 core-shell nanoparticles were synthesized and to confirm the core-shell structure they were characterized by UV-vis, XRD, FTIR, TEM, and EDX. Our data confirm that core-shell type Ag@SiO2 nanoparticles maintain its ability to kill cancer cells upon light irradiation. This shows that SiO2 shell may not only prevent aggregation but it also may enhance the photodynamic activity of Ag nanoparticles.

Transition from Linear to Circular Motion in Active Spherical-Cap Colloids.

Nonspherical self-propelling colloidal particles offer many possibilities for creating a variety of active motions. In this work, we report on the transition from linear to circular motion of active spherical-cap particles near a substrate. Self-propulsion is induced by self-diffusiophoresis by catalytic decomposition of hydrogen peroxide (H2O2) on one side of the particle. Asymmetric distribution of reaction products combined with the asymmetric shape of the particle gives rise to two types of motions depending upon the relative orientation of the particle with respect to the underlying substrate. At a low concentration of H2O2, linear active motion is observed, whereas increasing the H2O2 concentration leads to persistent circular motion. However, the speed of self-propulsion is nearly independent of the size of the particle. The study demonstrates the use of nonspherical particles to create linear and circular motion by varying the fuel concentration.

Crystal structures of 6a,6b,7,11a-tetra-hydro-6H,9H-spiro-[chromeno[3',4':3,4]pyrrolo-[1,2-c]thia-zole-11,3'-indoline]-2',6-dione and 5'-methyl-6a,6b,7,11a-tetra-hydro-6H,9H-spiro-[chromeno[3',4':3,4]pyrrolo-[1,2-c]thia-zole-11,3'-indoline]-2',6-dione.

The title compounds, C20H16N2O3S, (I), and C21H18N2O3S, (II), differ by the presence of a methyl group in position 5 on the 1H-indole-2-one ring of compound (II). The two compounds have a structural overlap r.m.s. deviation of 0.48 Å. There is a significant difference in the conformation of the thia-zolidine ring: it has a twisted conformation on the fused N-C bond in (I), but an envelope conformation in compound (II) with the S atom as the flap. The planar pyrrolidine ring of the indole ring system is normal to the mean plane of the five-membered pyrrolidine ring of the pyrrolo-thia-zole unit in both compounds, with dihedral angles of 88.71 (9) and 84.59 (8)°. The pyran rings in both structures have envelope conformations with the methyl-ene C atom adjacent to the C=O group as the flap. In both compounds, there is a short intra-molecular C-H⋯O contact present. In the crystal of (I), mol-ecules are linked by C-H⋯O hydrogen bonds forming chains propagating along the b-axis direction. The chains are linked by N-H⋯π inter-actions, forming layers parallel to (10). In the crystal of (II), mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers which are linked by C-H⋯O hydrogen bonds to form a three-dimensional structure.

Long-range molecular dynamics show that inactive forms of Protein Kinase A are more dynamic than active forms.

Many protein kinases are characterized by at least two structural forms corresponding to the highest level of activity (active) and low or no activity, (inactive). Further, protein dynamics is an important consideration in understanding the molecular and mechanistic basis of enzyme function. In this work, we use protein kinase A (PKA) as the model system and perform microsecond range molecular dynamics (MD) simulations on six variants which differ from one another in terms of active and inactive form, with or without bound ligands, C-terminal tail and phosphorylation at the activation loop. We find that the root mean square fluctuations in the MD simulations are generally higher for the inactive forms than the active forms. This difference is statistically significant. The higher dynamics of inactive states has significant contributions from ATP binding loop, catalytic loop, and αG helix. Simulations with and without C-terminal tail show this differential dynamics as well, with lower dynamics both in the active and inactive forms if C-terminal tail is present. Similarly, the dynamics associated with the inactive form is higher irrespective of the phosphorylation status of Thr 197. A relatively stable stature of active kinases may be better suited for binding of substrates and detachment of the product. Also, phosphoryl group transfer from ATP to the phosphosite on the substrate requires precise transient coordination of chemical entities from three different molecules, which may be facilitated by the higher stability of the active state.

Isomorphous diethyl 1-(4-chloro-benz-yl)-4-(4-chloro-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate and its 1-(4-methyl-benz-yl)-4-(4-methyl-phen-yl)-substituted analogue obeying the chloro-methyl exchange rule.

Accurate studies on the effect of substituents on the crystal packing are essential for understanding the inter-molecular inter-actions and thus paving the way to crystal structure prediction. The crystal structures of diethyl 1-(4-chloro-benz-yl)-4-(4-chloro-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thiazine-1,3-di-carboxyl-ate, C26H29Cl2NO6S, (I), and its isomorphous pair diethyl 1-(4-methyl-benz-yl)-4-(4-methyl-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate, C28H35NO6S, (II), are described. The mol-ecular aggregation patterns appear to be strikingly similar despite changes in the substituents, with a Cl atom in (I) being replaced by a methyl group in (II). Inspite of the chemical modifications, the structures of (I) and (I) are isomorphous, isostructural and found to obey the chlorine-methyl exchange rule. Both the structures feature C-H⋯O hydrogen bonding. However, a distinguishing feature between (I) and (II) is observed in the conformation of the pyrrole rings where the twist occurs on different C-N bonds. Hirshfeld analysis of both structures is presented and discussed.

Assessment of a conduction-repolarisation metric to predict Arrhythmogenesis in right ventricular disorders.

BACKGROUND: The re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry. This study aimed to test feasibility of an RVI-based algorithm to predict the earliest endocardial activation site of ventricular tachycardia (VT) during electrophysiological studies and occurrence of haemodynamically significant ventricular arrhythmias in follow-up. METHODS: Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n = 11), Brugada Syndrome (BrS) (n = 13) and focal RV outflow tract VT (n = 9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array in the RV. RESULTS: Lowest values of RVI co-localised with VT earliest activation site in ARVC/BrS but not in focal VT. The distance between region of lowest RVI and site of VT earliest site (Dmin) was lower in ARVC/BrS than in focal VT (6.8 ±â€¯6.7 mm vs 26.9 ±â€¯13.3 mm, p = 0.005). ARVC/BrS patients with inducible VT had lower Global-RVI (RVIG) than those who were non-inducible (-54.9 ±â€¯13.0 ms vs -35.9 ±â€¯8.6 ms, p = 0.005) or those with focal VT (-30.6 ±â€¯11.5 ms, p = 0.001). Patients were followed up for 112 ±â€¯19 months. Those with clinical VT events had lower Global-RVI than both ARVC and BrS patients without VT (-54.5 ±â€¯13.5 ms vs -36.2 ±â€¯8.8 ms, p = 0.007) and focal VT patients (-30.6 ±â€¯11.5 ms, p = 0.002). CONCLUSIONS: RVI reliably identifies the earliest RV endocardial activation site of VT in BrS and ARVC but not focal ventricular arrhythmias and predicts the incidence of haemodynamically significant arrhythmias. Therefore, RVI may be of value in predicting VT exit sites and hence targeting of re-entrant arrhythmias.

Formulation and biological actions of nano-bioglass ceramic particles doped with Calcarea phosphorica for bone tissue engineering.

The improvisation of the treatment procedures for treating the various kind of bone defects such as, bone or dental trauma and for diseases such as osteoporosis, osteomyelitis etc., need the suitable and promising biomaterials with resemblance of bone components. Bioactive glass ceramic (BGC) has recently acquired great attention as the most promising biomaterials; hence it has been widely applied as a filler material for bone tissue regeneration. Because it elicts specific biological responses after implantation in addition more potential in formation of strong interface with both hard and soft tissues by dissolution of calcium and phosphate ions. Hence, the current focus in treating the bone defects by orchestrating the biomaterial in combination of alternative medicine such as homeopathic remedies with biomaterials to prevent the adverse effects at minimal concentrations. So the current study was focused on constructing the nano-bioglass ceramic particles (nBGC) doped with novel homeopathic remedy Calcarea phosphorica for dental and bone therapeutic implants. The nBGC particles were synthesized by sol-gel method and reinforced with commercially available Calcarea phosphorica. The synthesized particles were characterized by SEM, DLS, EDS, FT-IR, and XRD studies. The SEM and DLS were shown the size of the particles at nano scale, also the EDS, and FT-IR investigations indicated that the Calcarea phosphorica was integrated with nBGC particles and also the crystalline nature of particles was confirmed by XRD studies. Both nBGC and Calcarea phosphorica doped nBGC (CP-nBGC) were found to be non toxic to mouse mesenchymal stem cells at lower concentrations and also illustrated the better bone forming ability in vitro.

Polymer coated mesoporous ceramic for drug delivery in bone tissue engineering.

Treatment strategy for various bone fracture and defects the researchers are focusing to develop a new carrier for delivering the drug into injured area with controlled and sustained manner using biomaterials with dynamic architecture orientation. Ceramic materials are resembled with bone compositional architecture and better bioactivity, degradability as well as antimicrobial activity made its enormous application in bone tissue engineering (BTE). Current focus in regenerative medicine were orchestration of biomaterials with the capacity of loading the drugs, growth factors, ionic components to promote better healing of bone tissue. Mesoporous type materials owed a great look towards the delivery of drugs, growth factors, etc in BTE because of its unique geometry. So the guest molecules loaded with geometrically organized ceramics would deliver onto the site of injury in controlled manner also the guiding and regulation of delivery of molecules have been controlled with the polymers response to different stimulation or biochemical factors as either scaffold or encapsulated particles for bone regeneration. Hence the review aims to describing the recent progress in bone tissue engineering using the ceramic based mesoporous materials encapsulated with polymers respond to different physiochemical stimulation for the efficient and controlled delivery of drug/growth factors for better bone healing.

Registered Replication Report: Rand, Greene, and Nowak (2012).

In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of -0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.

A propensity matched case-control study comparing efficacy, safety and costs of the subcutaneous vs. transvenous implantable cardioverter defibrillator.

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICD) have become more widely available. However, comparisons with conventional transvenous ICDs (TV-ICD) are scarce. METHODS: We conducted a propensity matched case-control study including all patients that underwent S-ICD implantation over a five-year period in a single tertiary centre. Controls consisted of all TV-ICD implant patients over a contemporary time period excluding those with pacing indication, biventricular pacemakers and those with sustained monomorphic ventricular tachycardia requiring anti-tachycardia pacing. Data was collected on device-related complications and mortality rates. A cost efficacy analysis was performed. RESULTS: Sixty-nine S-ICD cases were propensity matched to 69 TV-ICD controls. During a mean follow-up of 31±19 (S-ICD) and 32±21months (TV-ICD; p=0.88) there was a higher rate of device-related complications in the TV-ICD group predominantly accounted for by lead failures (n=20, 29% vs. n=6, 9%; p=0.004). The total mean cost for each group, including the complication-related costs was £9967±4511 ($13,639±6173) and £12,601±1786 ($17,243±2444) in the TV-ICD and S-ICD groups respectively (p=0.0001). Even though more expensive S-ICD was associated with a relative risk reduction of device-related complication of 70% with a HR of 0.30 (95%CI 0.12-0.76; p=0.01) compared to TV-ICDs. CONCLUSIONS: TV-ICDs are associated with increased device-related complication rates compared to a propensity matched S-ICD group during a similar follow-up period. Despite the existing significant difference in unit cost of the S-ICD, overall S-ICD costs may be mitigated versus TV-ICDs over a longer follow-up period.