List Decoding of Matrix-Product Codes from nested codes: an application to Quasi-Cyclic codes

A list decoding algorithm for matrix-product codes is provided when $C_1,..., C_s$ are nested linear codes and $A$ is a non-singular by columns matrix. We estimate the probability of getting more than one codeword as output when the constituent codes are Reed-Solomon codes. We extend this list decoding algorithm for matrix-product codes with polynomial units, which are quasi-cyclic codes. Furthermore, it allows us to consider unique decoding for matrix-product codes with polynomial units

Aggregatibacter Actinomycetemcomitans Leukotoxin is Post-Translationally Modified by Addition of Either Saturated or Hydroxylated Fatty Acyl Chains

Aggregatibacter actinomycetemcomitans, a common inhabitant of the human upper aerodigestive tract, produces a repeat in toxin (RTX), leukotoxin (LtxA). The LtxA is transcribed as a 114-kDa inactive protoxin with activation being achieved by attachment of short chain fatty acyl groups to internal lysine residues. Methyl esters of LtxA that were isolated from A. actinomycetemcomitans strains JP2 and HK1651 and subjected to gas chromatography/mass spectrometry contained palmitoyl (C16:0, 27-29%) and palmitolyl (C16:1 cis Δ9, 43-44%) fatty acyl groups with smaller quantities of myristic (C14:0, 14%) and stearic (C18:0, 12-14%) fatty acids. Liquid chromatography/mass spectrometry of tryptic peptides from acylated and unacylated recombinant LtxA confirmed that Lys562 and Lys687 are the sites of acyl group attachment. During analysis of recombinant LtxA peptides, we observed peptide spectra that were not observed as part of the RTX acylation schemes of either Escherichia coliα-hemolysin or Bordetella pertussis cyclolysin. Mass calculations of these spectra suggested that LtxA was also modified by the addition of monohydroxylated forms of C14 and C16 acyl groups. Multiple reaction monitoring mass spectrometry identified hydroxymyristic and hydroxypalmitic acids in wild-type LtxA methyl esters. Single or tandem replacement of Lys562 and Lys687 with Arg blocks acylation, resulting in a \u3e75% decrease in cytotoxicity when compared with wild-type toxin, suggesting that these post-translational modifications are playing a critical role in LtxA-mediated target cell cytotoxicity. © 2011 John Wiley & Sons A/S

Aggregatibacter Actinomycetemcomitans Leukotoxin is Post-Translationally Modified by Addition of Either Saturated or Hydroxylated Fatty Acyl Chains

Aggregatibacter actinomycetemcomitans, a common inhabitant of the human upper aerodigestive tract, produces a repeat in toxin (RTX), leukotoxin (LtxA). The LtxA is transcribed as a 114-kDa inactive protoxin with activation being achieved by attachment of short chain fatty acyl groups to internal lysine residues. Methyl esters of LtxA that were isolated from A. actinomycetemcomitans strains JP2 and HK1651 and subjected to gas chromatography/mass spectrometry contained palmitoyl (C16:0, 27–29%) and palmitolyl (C16:1 cis Δ9, 43–44%) fatty acyl groups with smaller quantities of myristic (C14:0, 14%) and stearic (C18:0, 12–14%) fatty acids. Liquid chromatography/mass spectrometry of tryptic peptides from acylated and unacylated recombinant LtxA confirmed that Lys562 and Lys687 are the sites of acyl group attachment. During analysis of recombinant LtxA peptides, we observed peptide spectra that were not observed as part of the RTX acylation schemes of either Escherichia coli α-hemolysin or Bordetella pertussis cyclolysin. Mass calculations of these spectra suggested that LtxA was also modified by the addition of monohydroxylated forms of C14 and C16 acyl groups. Multiple reaction monitoring mass spectrometry identified hydroxymyristic and hydroxypalmitic acids in wild-type LtxA methyl esters. Single or tandem replacement of Lys562 and Lys687 with Arg blocks acylation, resulting in a \u3e75% decrease in cytotoxicity when compared with wild-type toxin, suggesting that these posttranslational modifications are playing a critical role in LtxA-mediated target cell cytotoxicity

Whole-Body Hypothermia, Cerebral Magnetic Resonance Biomarkers, and Outcomes in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy Born at Tertiary Care Centers vs Other Facilities: A Nested Study Within a Randomized Clinical Trial

IMPORTANCE: The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown. OBJECTIVE: To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn). Design, Setting, and PARTICIPANTS: This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks' gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020. Exposure: 3T MR imaging, MR spectroscopy, and diffusion tensor imaging. MAIN OUTCOMES AND MEASURES: Thalamic N-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months. RESULTS: Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg; P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%; P = .01), and more likely to be intubated at birth (78.9% vs 29.1%; P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%; P = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], -0.28; 95% CI, -1.62 to 1.07; P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, -0.62 to 0.71; P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08; P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09; P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41). CONCLUSIONS AND RELEVANCE: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02387385

The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO) to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH.Methods/design: This trial is designed as a multicentre trial in which 400 infants (200 in each arm) will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension.Discussion: To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity.Trial registration: Netherlands Trial Register (NTR): NTR1310

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth,predicts adverse neurodevelopmental outcomeeighteenmonths after neonatal encephalopathy.We performed next generation sequencing on whole blood ribonucleic acid obtained within sixhours of birth from the first 47encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX)trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1and SMC4 werethe most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatoninand polo-like kinase in babieswith adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanismsand identify novel therapeutic targetsfor neuroprotection

Improving emergency treatment for patients with acute stroke: the PEARS research programme, including the PASTA cluster RCT

Background Intravenous thrombolysis and intra-arterial thrombectomy are proven emergency treatments for acute ischaemic stroke, but they require rapid delivery to selected patients within specialist services. National audit data have shown that treatment provision is suboptimal. Objectives The aims were to (1) determine the content, clinical effectiveness and day 90 cost-effectiveness of an enhanced paramedic assessment designed to facilitate thrombolysis delivery in hospital and (2) model thrombectomy service configuration options with optimal activity and cost-effectiveness informed by expert and public views. Design A mixed-methods approach was employed between 2014 and 2019. Systematic reviews examined enhanced paramedic roles and thrombectomy effectiveness. Professional and service user groups developed a thrombolysis-focused Paramedic Acute Stroke Treatment Assessment, which was evaluated in a pragmatic multicentre cluster randomised controlled trial and parallel process evaluation. Clinicians, patients, carers and the public were surveyed regarding thrombectomy service configuration. A decision tree was constructed from published data to estimate thrombectomy eligibility of the UK stroke population. A matching discrete-event simulation predicted patient benefits and financial consequences from increasing the number of centres. Setting The paramedic assessment trial was hosted by three regional ambulance services (in north-east England, north-west England and Wales) serving 15 hospitals. Participants A total of 103 health-care representatives and 20 public representatives assisted in the development of the paramedic assessment. The trial enrolled 1214 stroke patients within 4 hours of symptom onset. Thrombectomy service provision was informed by a Delphi exercise with 64 stroke specialists and neuroradiologists, and surveys of 147 patients and 105 public respondents. Interventions The paramedic assessment comprised additional pre-hospital information collection, structured hospital handover, practical assistance up to 15 minutes post handover, a pre-departure care checklist and clinician feedback. Main outcome measures The primary outcome was the proportion of patients receiving thrombolysis. Secondary outcomes included day 90 health (poor status was a modified Rankin Scale score of > 2). Economic outputs reported the number of cases treated and cost-effectiveness using quality-adjusted life-years and Great British pounds. Data sources National registry data from the Sentinel Stroke National Audit Programme and the Scottish Stroke Care Audit were used. Review methods Systematic searches of electronic bibliographies were used to identify relevant literature. Study inclusion and data extraction processes were described using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results The paramedic assessment trial found a clinically important but statistically non-significant reduction in thrombolysis among intervention patients, compared with standard care patients [197/500 (39.4%) vs. 319/714 (44.7%), respectively] (adjusted odds ratio 0.81, 95% confidence interval 0.61 to 1.08; p = 0.15). The rate of poor health outcomes was not significantly different, but was lower in the intervention group than in the standard care group [313/489 (64.0%) vs. 461/690 (66.8%), respectively] (adjusted odds ratio 0.86, 95% confidence interval 0.60 to 1.2; p = 0.39). There was no difference in the quality-adjusted life-years gained between the groups (0.005, 95% confidence interval –0.004 to 0.015), but total costs were significantly lower for patients in the intervention group than for those in the standard care group (–£1086, 95% confidence interval –£2236 to –£13). It has been estimated that, in the UK, 10,140–11,530 patients per year (i.e. 12% of stroke admissions) are eligible for thrombectomy. Meta-analysis of published data confirmed that thrombectomy-treated patients were significantly more likely to be functionally independent than patients receiving standard care (odds ratio 2.39, 95% confidence interval 1.88 to 3.04; n = 1841). Expert consensus and most public survey respondents favoured selective secondary transfer for accessing thrombectomy at regional neuroscience centres. The discrete-event simulation model suggested that six new English centres might generate 190 quality-adjusted life-years (95% confidence interval –6 to 399 quality-adjusted life-years) and a saving of £1,864,000 per year (95% confidence interval –£1,204,000 to £5,017,000 saving per year). The total mean thrombectomy cost up to 72 hours was £12,440, mostly attributable to the consumables. There was no significant cost difference between direct admission and secondary transfer (mean difference –£368, 95% confidence interval –£1016 to £279; p = 0.26). Limitations Evidence for paramedic assessment fidelity was limited and group allocation could not be masked. Thrombectomy surveys represented respondent views only. Simulation models assumed that populations were consistent with published meta-analyses, included limited parameters reflecting underlying data sets and did not consider the capital costs of setting up new services. Conclusions Paramedic assessment did not increase the proportion of patients receiving thrombolysis, but outcomes were consistent with improved cost-effectiveness at day 90, possibly reflecting better informed treatment decisions and/or adherence to clinical guidelines. However, the health difference was non-significant, small and short term. Approximately 12% of stroke patients are suitable for thrombectomy and widespread provision is likely to generate health and resource gains. Clinician and public views support secondary transfer to access treatment. Future work Further evaluation of emergency care pathways will determine whether or not enhanced paramedic assessment improves hospital guideline compliance. Validation of the simulation model post reconfiguration will improve precision and describe wider resource implications. Trial registration This trial is registered as ISRCTN12418919 and the systematic review protocols are registered as PROSPERO CRD42014010785 and PROSPERO CRD42015016649

Evaluation of a text supported weight maintenance programme ‘Lighten Up Plus’ following a weight reduction programme: randomised controlled trial

Background Many overweight people find it difficult to maintain weight loss after attending a weight reduction programme. Self-weighing and telephone support are known to be useful methods for self-monitoring for weight loss. We examined the effectiveness of an SMS-text messaging based weight maintenance programme to encourage regular self-weighing in adults who had completed a 12 week commercial weight loss programme. Methods Randomised controlled trial of 380 obese or overweight men and women. The intervention group (n=190) received a single maintenance support phone call and SMS-text based weight maintenance messages over 12 weeks to encourage regular self-weighing after completing their weight loss programme. The primary outcome was change in weight at nine months follow up. Results Our sample (N=380) had a mean age of 47.4 years (SD 13.4), mean baseline weight and BMI of 93.1kg (16.1) and 34.4 kg/m2 (5.0) respectively, as well as majority female (87.3%) and White British (80.0%). Using intention to treat analysis both groups regained weight at nine months follow up; the intervention group regained an average of 1.36 kg while the control group regained 1.81 kg. Adjusting for covariates resulted in a mean difference of 0.45 kg (95% CI -0.78, 1.67) favouring the intervention group at nine month follow up. Conclusions We found no evidence that an SMS based weight maintenance intervention encouraging adults to weigh themselves weekly prevented weight regain at three or nine months after completing a commercial weight loss programme. <br/

Breaking bad habits by improving executive function in individuals with obesity

Background: Two primary factors that contribute to obesity are unhealthy eating and sedentary behavior. These behaviors are particularly difficult to change in the long-term because they are often enacted habitually. Cognitive Remediation Therapy has been modified and applied to the treatment of obesity (CRT-O) with preliminary results of a randomized controlled trial demonstrating significant weight loss and improvements in executive function. The objective of this study was to conduct a secondary data analysis of the CRT-O trial to evaluate whether CRT-O reduces unhealthy habits that contribute to obesity via improvements in executive function. Method: Eighty participants with obesity were randomized to CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and Trail Making Task) and unhealthy eating and sedentary behavior habits were administered at baseline, post-intervention and at 3 month follow-up. Results: Participants receiving CRT-O demonstrated improvements in both measures of executive function and reductions in both unhealthy habit outcomes compared to control. Mediation analyses revealed that change in one element of executive function performance (Wisconsin Card Sort Task perseverance errors) mediated the effect of CRT-O on changes in both habit outcomes. Conclusion: These results suggest that the effectiveness of CRT-O may result from the disruption of unhealthy habits made possible by improvements in executive function. In particular, it appears that cognitive flexibil ity, as measured by the Wisconsin Card Sort task, is a key mechanism in this process. Improving cognitive flexibility may enable individuals to capitalise on interruptions in unhealthy habits by adjusting their behavior in line with their weight loss goals rather than persisting with an unhealthy choice. Trial registration: The RCT was registered with the Australian New Zealand Registry of Clinical Trials (trial id: ACTRN12613000537752)