Variable Block Length Research Articles

Tailoring copolymer architectures and macromolecular interactions for enhanced nanotherapeutic delivery: A design-by-architecture approach

Amphiphilic copolymers with precise macromolecular topologies are crucial in nanomedicine for enhancing drug delivery by improving solubilization, stabilization, and therapeutic efficacy on target tissues. This study employs a design-by-architecture approach to identify factors influencing interactions between synthesized macromolecules and biological systems for optimal drug nanodelivery. Copolymers combining poly(ε-caprolactone) blocks and poly(polyethylene glycol methacrylate) or poly(glycerol methacrylate), were synthesized to investigate how architectural adjustments impact self-assembly, nanoparticle size, drug loading, and biomolecule interactions. Linear and brush block copolymers with varied block lengths were studied for their self-assembly behavior in aqueous environments. Both copolymer types formed smaller nanoparticles with extended hydrophilic blocks, with brush block copolymers showing superior performance due to their peculiar macromolecular architecture. Incorporating ‘clickable’ glycidyl units within the hydrophilic block minimally affected particle size. Controlled functionalization with thiol groups resulted in stable nanoparticles with enhanced size reduction and mucoadhesive properties, potentially improving targeted drug delivery and therapeutic effects.

Photoresponsive Block Copolymer Nanostructures through Implementation of Arylazopyrazoles.

Responsive nanomaterials that can undergo reversible changes in morphology are interesting for the development of functional materials that interact with and respond to their environment. Amphiphilic block copolymers are well-known for their ability to create a wide range of supramolecular nanostructures in solution. Arylazopyrazoles (AAPs) are versatile molecular photoswitches, which change their configuration and hydrophobicity upon irradiation with UV light (365 nm, Z isomer, less hydrophobic) and green light (520 nm, E isomer, more hydrophobic). In this work, photoswitchable block copolymers containing arylazopyrazole tetraethylene glycol methacrylate (AAPMA) and oligo(ethylene glycol) methacrylate (OEGMA) forming amphiphilic POEGMA-b-PAAPMA with varying block lengths are prepared by RAFT polymerization. The photochemical properties of AAP persist in the polymers. Due to their amphiphilic structure, the polymers self-assemble into supramolecular morphologies in water. Remarkably, photoisomerization results in a reversible change in the self-assembly behavior. Specifically, spherical and cylindrical micelles are observed for POEGMA33-b-PAAPMA47 when illuminated with green or UV light during assembly. Furthermore, the morphology of assembled structures can be reversibly switched by subsequent irradiation with UV and green light.

Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial

Whether high-dose cytarabine-based salvage chemotherapy, administered to induce complete remission in patients with poor responsive or relapsed acute myeloid leukaemia scheduled for allogeneic haematopoietic stem-cell transplantation (HSCT) after intensive conditioning confers a survival advantage, is unclear. To test salvage chemotherapy before allogeneic HSCT, patients aged between 18 and 75 years with non-favourable-risk acute myeloid leukaemia not in complete remission after first induction or untreated first relapse were randomly assigned 1:1 to remission induction with high-dose cytarabine (3 g/m2 intravenously, 1 g/m2 intravenously for patients >60 years or with a substantial comorbidity) twice daily on days 1-3 plus mitoxantrone (10 mg/m2 intravenously) on days 3-5 or immediate allogeneic HSCT for the disease control group. Block randomisation with variable block lengths was used and patients were stratified by age, acute myeloid leukaemia risk, and disease status. The study was open label. The primary endpoint was treatment success, defined as complete remission on day 56 after allogeneic HSCT, with the aim to show non-inferiority for disease control compared with remission induction with a non-inferiority-margin of 5% and one-sided type 1 error of 2·5%. The primary endpoint was analysed in both the intention-to-treat (ITT) population and in the per-protocol population. The trial is completed and was registered at ClinicalTrials.gov, NCT02461537. 281 patients were enrolled between Sept 17, 2015, and Jan 12, 2022. Of 140 patients randomly assigned to disease control, 135 (96%) proceeded to allogeneic HSCT, 97 (69%) after watchful waiting only. Of 141 patients randomly assigned to remission induction, 134 (95%) received salvage chemotherapy and 128 (91%) patients subsequently proceeded to allogeneic HSCT. In the ITT population, treatment success was observed in 116 (83%) of 140 patients in the disease control group versus 112 (79%) of 141 patients with remission induction (test for non-inferiority, p=0·036). Among per-protocol treated patients, treatment success was observed in 116 (84%) of 138 patients with disease control versus 109 (81%) of 134 patients in the remission induction group (test for non-inferiority, p=0·047). The difference in treatment success between disease control and remission induction was estimated as 3·4% (95% CI -5·8 to 12·6) for the ITT population and 2·7% (-6·3 to 11·8) for the per-protocol population. Fewer patients with disease control compared with remission induction had non-haematological adverse events grade 3 or worse (30 [21%] of 140 patients vs 86 [61%] of 141 patients, χ2 test p<0·0001). Between randomisation and the start of conditioning, with disease control two patients died from progressive acute myeloid leukaemia and zero from treatment-related complications, and with remission induction two patients died from progressive acute myeloid leukaemia and two from treatment-related complications. Between randomisation and allogeneic HSCT, patients with disease control spent a median of 27 days less in hospital than those with remission induction, ie, the median time in hospital was 15 days (range 7-64) versus 42 days (27-121, U test p<0·0001), respectively. Non-inferiority of disease control could not be shown at the 2·5% significance level. The rate of treatment success was also not statistically better for patients with remission induction. Watchful waiting and immediate transplantation could be an alternative for fit patients with poor response or relapsed acute myeloid leukaemia who have a stem cell donor available. More randomised controlled intention-to-transplant trials are needed to define the optimal treatment before transplantation for patients with active acute myeloid leukaemia. DKMS and the Gert and Susanna Mayer Stiftung Foundation.

Effect of BCG vaccination against Mycobacterium tuberculosis infection in adult Brazilian health-care workers: a nested clinical trial

The effectiveness of BCG vaccine for adult pulmonary tuberculosis remains uncertain. In this study, we aimed to evaluate the effect of vaccination with BCG-Denmark to prevent initial and sustained interferon-γ release assay conversion in Brazilian health-care workers. This substudy is a nested randomised controlled trial embedded within the BRACE trial (NCT04327206). Specifically, this substudy enrolled Brazilian health-care workers (aged ≥18 years) from three sites in Brazil (Manaus, Campo Grande, and Rio de Janeiro) irrespective of previously receiving BCG vaccination. Participants were excluded if they had contraindications to BCG vaccination, more than 1 month of treatment with specific tuberculosis treatment drugs, previous adverse reactions to BCG, recent BCG vaccination, or non-compliance with assigned interventions. Those eligible were randomly assigned (1:1) to either the BCG group (0·1 mL intradermal injection of BCG-Denmark [Danish strain 1331; AJ Vaccines, Copenhagen]) or the placebo group (intradermal injection of 0·9% saline) using a web-based randomisation process in variable-length blocks (2, 4, or 6), and were stratified based on the study site, age (<40, ≥40 to <60, ≥60 years), and comorbidity presence (diabetes, chronic respiratory disease, cardiac condition, hypertension). Sealed syringes were used to prevent inadvertent disclosure of group assignments. The QuantiFERON-TB Gold (QFT) Plus test (Qiagen; Hilden, Germany) was used for baseline and 12-month tuberculosis infection assessments. The primary efficacy outcome was QFT Plus conversion (≥0·35 IU/mL) by 12 months following vaccination in participants who had a negative baseline result (<0·35 IU/mL). Between Oct 7, 2020, and April 12, 2021, 1985 (77·3%) of 2568 participants were eligible for QFT Plus assessment at 12 months and were included in this substudy; 996 (50·2%) of 1985 were in the BCG group and 989 (49·8%) were in the placebo group. Overall, 1475 (74·3%) of 1985 participants were women and 510 (25·7%) were men, and the median age was 39 years (IQR 32-47). During the first 12 months, QFT Plus conversion occurred in 66 (3·3%) of 1985 participants, with no significant differences by study site (p=0·897). Specifically, 34 (3·4%) of 996 participants had initial QFT conversion in the BCG group compared with 32 (3·2%) of 989 in the placebo group (risk ratio 1·09 [95% CI 0·67-1·77]; p=0·791). BCG-Denmark vaccination did not reduce initial QFT Plus conversion risk in Brazilian health-care workers. This finding underscores the need to better understand tuberculosis prevention in populations at high risk. Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the United Health Group Foundation, Epworth Healthcare, and individual donors. For the Portuguese translation of the abstract see Supplementary Materials section.

Sequence Detection with Variable Sampling Rate and Block Length Under ISI Channels

Sequence Detection with Variable Sampling Rate and Block Length Under ISI Channels

Stationary Jackknife

Variance estimation is an important aspect in statistical inference, especially in the dependent data situations. Resampling methods are ideal for solving this problem since these do not require restrictive distributional assumptions. In this paper, we develop a novel resampling method in the Jackknife family called the stationary jackknife. It can be used to estimate the variance of a statistic in the cases where observations are from a general stationary sequence. Unlike the moving block jackknife, the stationary jackknife computes the jackknife replication by deleting a variable length block and the length has a truncated geometric distribution. Under appropriate assumptions, we can show the stationary jackknife variance estimator is a consistent estimator for the case of the sample mean and, more generally, for a class of nonlinear statistics. Further, the stationary jackknife is shown to provide reasonable variance estimation for a wider range of expected block lengths when compared with the moving block jackknife by simulation.

LERMS: A Low-Latency and Reliable Downlink Packet-Level Encoding Transmission Method in Untrusted 5GA Edge Network.

The increasing demand for end-to-end low-latency and high-reliability transmissions between edge computing nodes and user elements in 5G Advance edge networks has brought new challenges to the transmission of data. In response, this paper proposes LERMS, a packet-level encoding transmission scheme designed for untrusted 5GA edge networks that may encounter malicious transmission situations such as data tampering, discarding, and eavesdropping. LERMS achieves resiliency against such attacks by using 5GA Protocol data unit (PDU) coded Concurrent Multipath Transfer (CMT) based on Lagrangian interpolation and Raptor's two-layer coding, which provides redundancy to eliminate the impact of an attacker's malicious behavior. To mitigate the increased queuing delay resulting from encoding in data blocks, LERMS is queue-aware with variable block length. Its strategy is modeled as a Markov chain and optimized using a matrix method. Numerical results demonstrate that LERMS achieves the optimal trade-off between delay and reliability while providing resiliency against untrusted edge networks.

Data reconstruction and recovery of deduplicated files having non-resident attributes in NTFS volume

The NTFS used in Windows Server operating system provides a function of removing duplicated areas by comparing them with other files in variable-length block units to use storage space efficiently. Although the data deduplication technology is already applied to the server systems such as cloud services, it is necessary to understand the operation of the Windows Server and the corresponding file system in order to view or extract files in digital forensic surveys. So in this paper, we analyze the process of deduplication and structure for reconstructing files with data deduplication function on the Windows Server using NTFS. Specific actions have structural differences depending on the version of the Windows Server. Until Windows Server 2012, deduplicated files with only resident attributes existed in the MFT entry. Still, in the 2016 and 2019, and 2022 versions released thereafter, deduplicated files have non-resident attributes, so the previous analysis results have a limitation in extracting files. Also, if the deduplicated file is deleted, even if the file carving technique is applied, it is stored in a fragmented state called a chunk. If a deduplicated file is deleted, and when its chunks are used by another file, chunks must remain allocated even if the file is deleted. This is different from traditional file recovery techniques, so we introduce a new perspective when recovering deduplicated files.

An Accelerated Variable Stage Size Carry Skip Adder Realization Using 1S1R Resistive Memory

In-memory computing is the method of running computer computations completely in memory. Memristive device (e.g., 1 selector-1 resistor (1S1R)) is preferably utilized for in-memory computing with the appearance of hybrid CMOS nano-crossbar arrays. The parallelism of resistive arrays is considered in parallel adder designs to reduce the critical path delay. However, they minimize latency at the cost of hardware resources. In addition, the resistive random-access memory (ReRAM) is suffered by sneak–path problem because of the incapability for accessing a specific cell without impeding its neighbors. To tackle this issue, an analytical model of Pt/TaO[Formula: see text]/TiO2/TaO[Formula: see text]/Pt selector device is developed and it is integrated with ReRAM model for reducing the sneak path current. In this paper, a novel mapping scheme is proposed for in-memory variable stage size carry skip adder (VSS-CSKA) to harness the parallelism of 1S1R resistive memory. The VSS-CSKA considers variable block lengths and uses basic Boolean functions as skip logic to improve the speed without requiring huge area. Also, the selector device is modeled by considering the Pt/TaO[Formula: see text]/TiO2/TaO[Formula: see text]/Pt crested barrier for suppressing the sneak current in the resistive memory. The macro-model of the 1S1R resistive memory model is modeled in Verilog-A netlist and the simulations are executed on Spectre circuit simulator from Cadence Virtuoso. The proposed in-memory adder reduced the latency to [Formula: see text] for [Formula: see text]-bit addition and it consumes less energy because of the minimization of sneak currents in 1S1R.

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial

Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. National Institute for Health Research.

Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST-AFNET 4 trial

Patients with atrial fibrillation and a history of stroke are at high risk of recurrent stroke and cardiovascular complications. In the EAST-AFNET 4 trial we showed that a systematic strategy of early rhythm control was associated with a lower risk of cardiovascular outcomes than usual care in patients with atrial fibrillation diagnosed in the past 12 months. In this pre-specified subgroup analysis we aimed to assess whether a strategy of early rhythm control is safe and can prevent adverse cardiovascular outcomes compared with usual care in such patients. EAST-AFNET 4 was a randomised, open-label trial with blinded-outcome assessment done at 135 hospitals and secondary care practices in 11 European countries. Adults with early atrial fibrillation (ie, diagnosed ≤12 months before enrolment) were randomly assigned (1:1) to either early rhythm control or usual care, with stratification according to site and variable block lengths used for concealment. The first primary outcome was time to first occurrence of the composite of cardiovascular death, ischaemic or haemorrhagic stroke, or hospital admission with worsening of heart failure or acute coronary syndrome. The second primary outcome was the number of nights spent in hospital in 1 year. The primary safety outcome was the composite of any death, stroke, or serious adverse events related to rhythm-control therapy. Here we present the results of these outcomes in patients with a history of stroke. Analyses were done in the intention-to-treat population. EAST-AFNET 4 is registered with ClinicalTrials.gov (NCT01288352), EudraCT (2010-021258-20), and ISRCTN (ISRCTN04708680). Between July 28, 2011, and Dec 30, 2016, 2789 patients were randomly assigned in the EAST-AFNET 4 trial to either early rhythm control (n=1395) or usual care (n=1394). Of these patients, five had no information on history of stroke and were excluded from this subgroup analysis. 217 (8%) patients had a history of stroke, of whom 110 were assigned to early rhythm control and 107 to usual care. The median age of participants with a history of stroke was 72·0 years (IQR 66·0-76·0). 95 (44%) participants were female and 122 (56%) were male. During a median follow-up of 4·7 years (3·5-6·4) for patients with a history of stroke, a first primary outcome event occurred in 18 (16%) of 110 patients in the early rhythm-control group (3·7 per 100 person-years) and 33 (31%) of 107 in the usual care group (7·4 per 100 person-years; hazard ratio [HR] 0·52, 95% CI 0·29-0·93). The mean number of nights spent in hospital per year was 5·1 (SD 13·2) for patients with a history of stroke assigned to early rhythm control and 6·6 (10·1) for those assigned to usual care (incidence rate ratio 0·87, 95% CI 0·55-1·38). Among patients with a history of stroke, primary safety events occurred in 17 (15%) patients in the early rhythm-control group versus 30 (28%) in the usual care group. In this prespecified subgroup analysis in patients with recently diagnosed atrial fibrillation and a history of stroke, the effects of early rhythm control were consistent with the findings of the primary analysis. As the evidence from this subgroup analysis is considered supportive and exploratory, further research is needed to confirm the safety and efficacy of this approach in patients with a history of stroke. German Ministry of Education and Research, German Center for Cardiovascular Research (DZHK), Atrial Fibrillation Network (AFNET), European Heart Rhythm Association, St Jude Medical-Abbott, Sanofi, and the German Heart Foundation.

Exploiting the lower disorder-to-order temperature in polystyrene-b-poly(n-butyl acrylate)-b-polystyrene triblock copolymers to increase their flow resistance at high temperature

This work focuses on the temperature-dependent structural and rheological characterization of polystyrene-b-poly(n-butyl acrylate)-b-polystyrene triblock copolymers (PS-b-PnBA-b-PS) in the melt and, in particular, on their ability to show a lower disorder-to-order temperature (LDOT). To this aim, copolymers of varying block lengths, but keeping the PnBA block as a major component, were synthesized. Small-angle x-ray scattering revealed that the copolymers with short PS blocks (∼10 kg/mol) approach an LDOT but do not cross it. At room temperature, these copolymers exhibit higher moduli compared to a PnBA homopolymer due to the reinforcing effect of the PS but are flowing at temperatures above the glass transition of the PS. Increasing the PS and PnBA block length, to keep the same PS fraction, induces more profound changes in the structural and viscoelastic behaviors. Such a copolymer crosses the LDOT, leading to a microphase-separated and ordered state at high temperature. Contrary to the copolymers with short PS blocks, the flow regime was not reached, even at temperatures well above the glass transition of the PS. Instead, a low-frequency plateau was observed in rheology, showing the increased lifetime of the microphase-separated PS domains. ABA triblock copolymers exhibiting an LDOT behavior could, thus, be of interest for the design of thermoplastic elastomers or pressure-sensitive adhesives that can resist the flow at high temperatures.

Synthesis and Evaluation of Thermoresponsive Renewable Lipid-Based Block Copolymers for Drug Delivery.

Polymeric micelle forming from self-assembly of amphiphilic macromolecules is one of the most potent drug delivery systems. Fatty acids, naturally occurring hydrophobic lipid components, can be considered as potential candidates for the fabrication of block copolymer micelles. However, examples of synthesis of responsive block copolymers using renewable fatty acids are scarce. Herein, we report the synthesis, characterization and testing of block copolymer micelles composed of a renewable fatty-acid-based hydrophobic block and thermoresponsive hydrophilic block for controlled drug delivery. The block copolymers of functionalized fatty acid and poly(N-isopropylacrylamide) (PNIPAM) were prepared via consecutive microwave-assisted reversible addition fragmentation chain transfer (RAFT) polymerization. The block copolymers with variable hydrophobic block length self-assembled in aqueous media and formed spherical nanoparticles of ~30 nm with low critical micelle concentration (CMC). To demonstrate the proof-of-concept, carbamazepine (CBZ) was used as a hydrophobic model drug to evaluate the performance of these micelles as nanocarriers. The in vitro drug release tests were carried out below (25 °C) and above (37 °C) the lower critical solution temperature (LCST) of the block copolymer. The drug release showed obvious temperature-triggered response and an accelerated drug release at 37 °C.

Surrogate-Assisted Particle Swarm Optimization for Evolving Variable-Length Transferable Blocks for Image Classification.

Deep convolutional neural networks (CNNs) have demonstrated promising performance on image classification tasks, but the manual design process becomes more and more complex due to the fast depth growth and the increasingly complex topologies of CNNs. As a result, neural architecture search (NAS) has emerged to automatically design CNNs that outperform handcrafted counterparts. However, the computational cost is immense, e.g., 22400 GPU-days and 2000 GPU-days for two outstanding NAS works named NAS and NASNet, respectively, which motivates this work. A new effective and efficient surrogate-assisted particle swarm optimization (PSO) algorithm is proposed to automatically evolve CNNs. This is achieved by proposing a novel surrogate model, a new method of creating a surrogate data set, and a new encoding strategy to encode variable-length blocks of CNNs, all of which are integrated into a PSO algorithm to form the proposed method. The proposed method shows its effectiveness by achieving the competitive error rates of 3.49% on the CIFAR-10 data set, 18.49% on the CIFAR-100 data set, and 1.82% on the SVHN data set. The CNN blocks are efficiently learned by the proposed method from CIFAR-10 within 3 GPU-days due to the acceleration achieved by the surrogate model and the surrogate data set to avoid the training of 80.1% of CNN blocks represented by the particles. Without any further search, the evolved blocks from CIFAR-10 can be successfully transferred to CIFAR-100, SVHN, and ImageNet, which exhibits the transferability of the block learned by the proposed method.

A novel multi‐functional model thermoset and PDA‐coated PU nanocomposite based on graphene and an amphiphilic block copolymer

AbstractThe need for multi‐functional biomaterials has driven researchers towards more complex multi‐component structures with tailor‐made surface modifications. In this research, thermoset polyurethanes (tPUs) of PCLy‐PEGx‐PCLy, with variable block lengths, and graphene were developed and further surface‐modified by Polydopamine (PDA) to improve cell adhesion. The viscoelastic and thermal properties of the tPUs were studied by DMA and DSC. The results proved the increased crystallization of the soft segments as the length of PCLy and PEGx blocks increased. The stress–strain results indicate the tPU nanocomposites possess high‐elastic modulus (38.46–96.17 MPa), and lower elongation (132.6%–375.9%) compared to thermoplastic PU nanocomposites. The tPU specimens proved to have very high shape recovery ratios (88.07%–94.93%). PDA surface deposition led to an increase in surface roughness and a change in surface topography. The PDA‐modified specimens showed significant improvement in protein adsorption and cell proliferation and also increased the hydrolytic degradation extent of the tPUs, proving the multi‐functional role of the biomaterials.

Conformational Transition and Interchain Association of Hypergraft HB-PS-g-PtBA Copolymer Chains with Varied Copolymer Compositions and Block Lengths in a Selective Solvent

Conformational Transition and Interchain Association of Hypergraft HB-PS-<i>g</i>-P<i>t</i>BA Copolymer Chains with Varied Copolymer Compositions and Block Lengths in a Selective Solvent

Image Encryption using Variable Length Blocks and Variable Length PK

The colored digital image is one of the most important and popular types of digital data for use in many vital applications, which requires the provision of safe methods to protect it from penetration operations and protect it from tampering and data thieves. In this research paper, a new method for protecting digital images of various types will be presented, which is characterized by ease of implementation and providing a high degree of security and protection for the digital image. A secret color image known only by the sender and receiver will be used as an image_ key, this image_key will be used to generate a private key to encrypt-decrypted any color image by applying image resizing. The private key will be variable, and will match the image block size. The image to be encrypted-decrypted will be divided into blocks, the block size will be variable and agree upon between the sender and receiver. The proposed method will be implemented, the obtained results will be analyzed to prove the efficiency, security level and quality parameters provided by the proposed method.

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial

ObjectiveTo test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics.DesignMulticentre, open label, randomised, non-inferiority...

Intravenous or oral antibiotic treatment in adults and children with cystic fibrosis and Pseudomonas aeruginosa infection: the TORPEDO-CF RCT.

People with cystic fibrosis are susceptible to pulmonary infection with Pseudomonas aeruginosa. This may become chronic and lead to increased mortality and morbidity. If treatment is commenced promptly, infection may be eradicated through prolonged antibiotic treatment. To compare the clinical effectiveness, cost-effectiveness and safety of two eradication regimens. This was a Phase IV, multicentre, parallel-group, randomised controlled trial. Seventy UK and two Italian cystic fibrosis centres. Participants were individuals with cystic fibrosis aged > 28 days old who had never had a P. aeruginosa infection or who had been infection free for 1 year. Fourteen days of intravenous ceftazidime and tobramycin or 3 months of oral ciprofloxacin. Inhaled colistimethate sodium was included in both regimens over 3 months. Consenting patients were randomly allocated to either treatment arm in a 1 : 1 ratio using simple block randomisation with random variable block length. The primary outcome was eradication of P. aeruginosa at 3 months and remaining free of infection to 15 months. Secondary outcomes included time to reoccurrence, spirometry, anthropometrics, pulmonary exacerbations and hospitalisations. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who had received at least one dose of any of the study drugs. Cost-effectiveness analysis explored the cost per successful eradication and the cost per quality-adjusted life-year. Between 5 October 2010 and 27 January 2017, 286 patients were randomised: 137 patients to intravenous antibiotics and 149 patients to oral antibiotics. The numbers of participants achieving the primary outcome were 55 out of 125 (44%) in the intravenous group and 68 out of 130 (52%) in the oral group. Participants randomised to the intravenous group were less likely to achieve the primary outcome; although the difference between groups was not statistically significant, the clinically important difference that the trial aimed to detect was not contained within the confidence interval (relative risk 0.84, 95% confidence interval 0.65 to 1.09; p = 0.184). Significantly fewer patients in the intravenous group (40/129, 31%) than in the oral group (61/136, 44.9%) were hospitalised in the 12 months following eradication treatment (relative risk 0.69, 95% confidence interval 0.5 to 0.95; p = 0.02). There were no clinically important differences in other secondary outcomes. There were 32 serious adverse events in 24 participants [intravenous: 10/126 (7.9%); oral: 14/146 (9.6%)]. Oral therapy led to reductions in costs compared with intravenous therapy (-£5938.50, 95% confidence interval -£7190.30 to -£4686.70). Intravenous therapy usually necessitated hospital admission, which accounted for a large part of this cost. Only 15 out of the 286 participants recruited were adults - partly because of the smaller number of adult centres participating in the trial. The possibility that the trial participants may be different from the rest of the cystic fibrosis population and may have had a better clinical status, and so be more likely to agree to the uncertainty of trial participation, cannot be ruled out. Intravenous antibiotics did not achieve sustained eradication of P. aeruginosa in a greater proportion of cystic fibrosis patients. Although there were fewer hospitalisations in the intravenous group during follow-up, this confers no advantage over the oral therapy group, as intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P. aeruginosa in cystic fibrosis. Future research studies should combine long-term follow-up with regimens to reduce reoccurrence after eradication. Current Controlled Trials ISRCTN02734162 and EudraCT 2009-012575-10. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 65. See the NIHR Journals Library website for further project information.

Interrogating the relationship between the microstructure of amphiphilic poly(ethylene glycol-b-caprolactone) copolymers and their colloidal assemblies using non-interfering techniques

Understanding the microstructural parameters of amphiphilic copolymers that control the formation and structure of aggregated colloids (e.g., micelles) is essential for the rational design of hierarchically structured systems for applications in nanomedicine, personal care and food formulations. Although many analytical techniques have been employed to study such systems, in this investigation we adopted an integrated approach using non-interfering techniques – diffusion nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) – to probe the relationship between the microstructure of poly(ethylene glycol-b-caprolactone) (PEG-b-PCL) copolymers [e.g., block molecular weight (MW) and the mass fraction of PCL (fPCL)] and the structure of their aggregates. Systematic trends in the self-assembly behaviour were determined using a large family of well-defined block copolymers with variable PEG and PCL block lengths (number-average molecular weights (Mn) between 2 and 10 and 0.5–15 kDa, respectively) and narrow dispersity (Ð < 1.12). For all of the copolymers, a clear transition in the aggregate structure was observed when the hydrophobic fPCL was increased at a constant PEG block Mn, although the nature of this transition is also dependent on the PEG block Mn. Copolymers with low Mn PEG blocks (2 kDa) were observed to transition from unimers and loosely associated unimers to metastable aggregates and finally, to cylindrical micelles as the fPCL was increased. In comparison, copolymers with PEG block Mn of between 5 and 10 kDa transitioned from heterogenous metastable aggregates to cylindrical micelles and finally, well-defined ellipsoidal micelles (of decreasing aspect ratios) as the fPCL was increased. In all cases, the diffusion NMR spectroscopy, DLS and synchrotron SAXS results provided complementary information and the grounds for a phase diagram relating copolymer microstructure to aggregation behaviour and structure. Importantly, the absence of commonly depicted spherical micelles has implications for applications where properties may be governed by shape, such as, cellular uptake of nanomedicine formulations.