Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.

BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed

A Flexible BCH decoder for Flash Memory Systems using Cascaded BCH codes

NAND ash memories are widely used in consumer electronics, such as tablets, personal computers, smartphones, and gaming systems. However, unlike other standard storage devices, these ash memories suffer from various random errors. In order to address these reliability issues, various error correction codes (ECC) are employed. Bose-Chaudhuri Hocquenghem (BCH) code is the most common ECC used to address the errors in modern ash memories. Because of the limitation of the realization of the BCH codes for more extensive error correction, the modern ash memory devices use Low-density parity-check (LDPC) codes for error correction scheme. The realization of the LDPC decoders have greater complexity than BCH decoders, so these ECC decoders are implemented within the ash memory device. This thesis analyzes the limitation imposed by the state of the art implementation of BCH decoders and proposes a cascaded BCH code to address these limitations. In order to support a variety of ash memory devices, there are three main challenges to be addressed for BCH decoders. First, the latency of the BCH decoders, in the case of no error scenario, should be less than 100us. Second, there should be flexibility in supporting different ECC block size; more precisely, the solution should be able to support 256, 512, 1024, and 2048 bytes of ECC block. Third, there should be flexibility in supporting different bit errors. A recent development with Graphical Processing Units (GPUs) has attracted many researchers to use GPUs for non-graphical implementation. These GPUs are used in many consumer electronics as part of the system on chip (SOC) configuration. In this thesis we studied the limitation imposed by different implementations (VLSI, GPU, and CPU) of BCH decoders, and we propose a cascaded BCH code implemented using a hybrid approach to overcome the limitations of the BCH codes. By splitting the implementation across VLSI and GPUs, we have shown in this thesis that this method can provide flexibility over the block size and the bit error to be corrected

Towards Reliable Automatic Protein Structure Alignment

A variety of methods have been proposed for structure similarity calculation, which are called structure alignment or superposition. One major shortcoming in current structure alignment algorithms is in their inherent design, which is based on local structure similarity. In this work, we propose a method to incorporate global information in obtaining optimal alignments and superpositions. Our method, when applied to optimizing the TM-score and the GDT score, produces significantly better results than current state-of-the-art protein structure alignment tools. Specifically, if the highest TM-score found by TMalign is lower than (0.6) and the highest TM-score found by one of the tested methods is higher than (0.5), there is a probability of (42%) that TMalign failed to find TM-scores higher than (0.5), while the same probability is reduced to (2%) if our method is used. This could significantly improve the accuracy of fold detection if the cutoff TM-score of (0.5) is used. In addition, existing structure alignment algorithms focus on structure similarity alone and simply ignore other important similarities, such as sequence similarity. Our approach has the capacity to incorporate multiple similarities into the scoring function. Results show that sequence similarity aids in finding high quality protein structure alignments that are more consistent with eye-examined alignments in HOMSTRAD. Even when structure similarity itself fails to find alignments with any consistency with eye-examined alignments, our method remains capable of finding alignments highly similar to, or even identical to, eye-examined alignments.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

INTERGROWTH-21st Gestational Dating and Fetal and Newborn Growth Standards in Peri-Urban Nairobi, Kenya: Quasi-Experimental Implementation Study Protocol.

BACKGROUND: The burden of preterm birth, fetal growth impairment, and associated neonatal deaths disproportionately falls on low- and middle-income countries where modern obstetric tools are not available to date pregnancies and monitor fetal growth accurately. The INTERGROWTH-21st gestational dating, fetal growth monitoring, and newborn size at birth standards make this possible. OBJECTIVE: To scale up the INTERGROWTH-21st standards, it is essential to assess the feasibility and acceptability of their implementation and their effect on clinical decision-making in a low-resource clinical setting. METHODS: This study protocol describes a pre-post, quasi-experimental implementation study of the standards at Jacaranda Health, a maternity hospital in peri-urban Nairobi, Kenya. All women with viable fetuses receiving antenatal and delivery services, their resulting newborns, and the clinicians caring for them from March 2016 to March 2018 are included. The study comprises a 12-month preimplementation phase, a 12-month implementation phase, and a 5-month post-implementation phase to be completed in August 2018. Quantitative clinical and qualitative data collected during the preimplementation and implementation phases will be assessed. A clinician survey was administered eight months into the implementation phase, month 20 of the study. Implementation outcomes include quantitative and qualitative analyses of feasibility, acceptability, adoption, appropriateness, fidelity, and penetration of the standards. Clinical outcomes include appropriateness of referral and effect of the standards on clinical care and decision-making. Descriptive analyses will be conducted, and comparisons will be made between pre- and postimplementation outcomes. Qualitative data will be analyzed using thematic coding and compared across time. The study was approved by the Amref Ethics and Scientific Review Committee (Kenya) and the Harvard University Institutional Review Board. Study results will be shared with stakeholders through conferences, seminars, publications, and knowledge management platforms. RESULTS: From October 2016 to February 2017, over 90% of all full-time Jacaranda clinicians (26/28) received at least one of the three aspects of the INTERGROWTH-21st training: gestational dating ultrasound, fetal growth monitoring ultrasound, and neonatal anthropometry standards. Following the training, implementation and evaluation of the standards in Jacaranda Health's clinical workflow will take place from March 2017 through March 5, 2018. Data analysis will be finalized, and results will be shared by August 2018. CONCLUSIONS: The findings of this study will have major implications on the national and global scale up of the INTERGROWTH-21st standards and on the process of scaling up global standards in general, particularly in limited-resource settings. REGISTERED REPORT IDENTIFIER: RR1-10.2196/10293

Impact of Pressure Biofeedback Analysis on Movement Control Exercise for Non-Specific Low Back Pain Treatment

Introduction: Low back pain in the class of prevalent musculoskeletal conditions, with almost 90% of cases classified as non-specific low back pain (NSLBP). Interestingly, the classification of mechanical low back pain (LBP) includes movement control deficits, specifically uncontrolled lumbo-pelvic movements, reflecting a deficit in controlling active movements in day-to-day life. The pressure biofeedback unit is accustomed to assess the functional stability of the trunk.Various traditional exercise protocols have been applied without making any sub-classifications. It is inappropriate to apply the same programs to all subjects with back pain. This study aims to identify the type of movement control impairments, assess them through a pressure biofeedback unit, and treat patients with corresponding movement control exercises tailored to their specific impairments.Aim: To ascertain the effect of movement control exercise (MCE) on NSLBP subjects using pressure biofeedback unit.Material and Methods: In this study, totally 40 subjects with non-specific low back pain (NSLBP) were selected. They were divided into two groups: an experimental group (Group A) and a control group (Group B), each consisting of 20 subjects, using proper randomization. Pre-test assessment was conducted using the movement control dysfunction test and a pressure biofeedback unit. Group A received treatment with movement control exercises, while Group B underwent spinal extension exercises and a back care program. Post-test assessment was carried out after the intervention. Results: The research study included 40 patients, with Group A comprising 20 patients receiving movement control exercises and Group B comprising 20 patients receiving spinal extension exercises. The results showed a reduction in pain, uncontrolled flexion, uncontrolled extension, and uncontrolled rotation patterns in both groups (p value, <0.05). However, the comparison between Group A and Group B revealed that movement control exercises resulted in greater improvement than spinal extension exercises.Conclusion: Based on the findings, it can be concluded that movement control exercises are more effective than spinal extension exercises in treating NSLBP

Semigroup Closures of Finite Rank Symmetric Inverse Semigroups

We introduce the notion of semigroup with a tight ideal series and investigate their closures in semitopological semigroups, particularly inverse semigroups with continuous inversion. As a corollary we show that the symmetric inverse semigroup of finite transformations $\mathscr{I}_\lambda^n$ of the rank $\leqslant n$ is algebraically closed in the class of (semi)topological inverse semigroups with continuous inversion. We also derive related results about the nonexistence of (partial) compactifications of classes of semigroups that we consider.Comment: With the participation of the new coauthor - Jimmie Lawson - the manuscript has been substantially revised and expanded. Accordingly, we have also changed the manuscript titl

Measurements of the branching fractions of B+→ppK+ decays

The branching fractions of the decay B+ → pp̄K+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component Mpp̄ < 2.85 GeV/c2 and the branching fractions via the resonant cc̄ states η c(1S) and ψ(2S) relative to the decay via a J/ψ intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained

Study of B0(s)→K0Sh+h′− decays with first observation of B0s→K0SK±π∓ and B0s→K0Sπ+π−

A search for charmless three-body decays of B 0 and B0s mesons with a K0S meson in the final state is performed using the pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV recorded by the LHCb experiment. Branching fractions of the B0(s)→K0Sh+h′− decay modes (h (′) = π, K), relative to the well measured B0→K0Sπ+π− decay, are obtained. First observation of the decay modes B0s→K0SK±π∓ and B0s→K0Sπ+π− and confirmation of the decay B0→K0SK±π∓ are reported. The following relative branching fraction measurements or limits are obtained B(B0→K0SK±π∓)B(B0→K0Sπ+π−)=0.128±0.017(stat.)±0.009(syst.), B(B0→K0SK+K−)B(B0→K0Sπ+π−)=0.385±0.031(stat.)±0.023(syst.), B(B0s→K0Sπ+π−)B(B0→K0Sπ+π−)=0.29±0.06(stat.)±0.03(syst.)±0.02(fs/fd), B(B0s→K0SK±π∓)B(B0→K0Sπ+π−)=1.48±0.12(stat.)±0.08(syst.)±0.12(fs/fd)B(B0s→K0SK+K−)B(B0→K0Sπ+π−)∈[0.004;0.068]at90%CL

Observation of the decay Bc→J/ψK+K−π+B_c \rightarrow J/\psi K^+ K^- \pi^+

The decay $B_c\rightarrow J/\psi K^+ K^- \pi^+$ is observed for the first time, using proton-proton collisions collected with the LHCb detector corresponding to an integrated luminosity of 3fb$^{-1}$. A signal yield of $78\pm14$ decays is reported with a significance of 6.2 standard deviations. The ratio of the branching fraction of \B_c \rightarrow J/\psi K^+ K^- \pi^+ decays to that of $B_c \rightarrow J/\psi \pi^+$ decays is measured to be $0.53\pm 0.10\pm0.05$, where the first uncertainty is statistical and the second is systematic.Comment: 18 pages, 2 figure

Evaluation of Remineralization of White Spot Lesions with Quercetin Nanoparticles:an in vitro Study

Background: This study explored the synthesis of quercetin nanoparticles (QNPs) and evaluated the remineralization effect of QNPs on artificial white spot lesions on extracted human teeth. Material and Methods: QNPs were successfully synthesized, and their size was measured. Seventy-six extracted human molars were divided into 4 groups of n=19 to undergo a 10-day pH cycling protocol: 1000 ppm fluoride solution as aqueous NaF (group 1), 6.5% w/v quercetin microparticle solution (group 2), 4000 ppm QNP (group 3) and deionized water (group 4). Vickers microhardness tester, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) and atomic force microscopy (AFM) were used to measure the surface microhardness (SMH), Ca:P ratio and surface roughness (Ra), respectively. Results: After remineralization, the SMH values were significantly different among all the experimental groups (p<0.001). The fluoride and QNP groups had significantly greater SMH values than the quercetin group. The AFM data showed a significant decrease, but the differences were not significant. The Ca:P values were significantly greater than those of the control in all 3 experimental groups, but the QNP and fluoride concentrations were significantly greater than those of quercetin. There were no significant differences between QNPs and fluoride according to any test. Conclusions: It can be concluded from the results of this study that QNPs have similar remineralization potential to f luoride and are more effective than quercetin