Moxibustion for cephalic version: a feasibility randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) has been used to correct a breech presentation. Evidence of effectiveness and safety from systematic reviews is encouraging although significant heterogeneity has been found among trials. We assessed the feasibility of conducting a randomised controlled trial of moxibustion plus usual care compared with usual care to promote cephalic version in women with a breech presentation, and examined the views of women and health care providers towards implementing a trial within an Australian context.</p> <p>Methods</p> <p>The study was undertaken at a public hospital in Newcastle, New South Wales, Australia. Women at 34-36.5 weeks of gestation with a singleton breech presentation (confirmed by ultrasound), were randomised to moxibustion plus usual care or usual care alone. The intervention was administered over 10 days. Clinical outcomes included cephalic presentation at birth, the need for ECV, mode of birth; perinatal morbidity and mortality, and maternal complications. Feasibility outcomes included: recruitment rate, acceptability, compliance and a sample size for a future study. Interviews were conducted with 19 midwives and obstetricians to examine the acceptability of moxibustion, and views on the trial.</p> <p>Results</p> <p>Twenty women were randomised to the trial. Fifty one percent of women approached accepted randomisation to the trial. A trend towards an increase in cephalic version at delivery (RR 5.0; 95% CI 0.7-35.5) was found for women receiving moxibustion compared with usual care. There was also a trend towards greater success with version following ECV. Two babies were admitted to the neonatal unit from the moxibustion group. Compliance with the moxibustion protocol was acceptable with no reported side effects. Clinicians expressed the need for research to establish the safety and efficacy of moxibustion, and support for the intervention was given to increase women's choices, and explore opportunities to normalise birth. The sample size for a future trial is estimated to be 381 women.</p> <p>Conclusion</p> <p>Our findings should be interpreted with caution as the study was underpowered to detect statistical differences between groups. Acceptance by women and health professionals towards moxibustion suggest further research is warranted.</p> <p>Trial Registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000985280.aspx">ACTRN12609000985280</a></p

Characterization of gastric mucosa biopsies reveals alterations in Huntington's Disease

Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry. In order to investigate possible histological differences related to gastric acid production, we evaluated the cell density of acid producing parietal cells, as well as gastrin producing cells (the endocrine cell controlling parietal cell function). In addition, we looked at chief cells and somatostatin-containing cells. In gastric mucosa from HD subjects, compared to control subject biopsies, a reduced expression of gastrin (a marker of G cells) was found. This is in line with previous HD mouse studies showing reduction of GI tract neuropeptides

Complex chloroplast RNA metabolism: just debugging the genetic programme?

<p>Abstract</p> <p>Background</p> <p>The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity.</p> <p>Results</p> <p>We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants.</p> <p>Conclusion</p> <p>Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions.</p

Readout of a quantum processor with high dynamic range Josephson parametric amplifiers

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure

Suppressing quantum errors by scaling a surface code logical qubit

Practical quantum computing will require error rates that are well below what is achievable with physical qubits. Quantum error correction offers a path to algorithmically-relevant error rates by encoding logical qubits within many physical qubits, where increasing the number of physical qubits enhances protection against physical errors. However, introducing more qubits also increases the number of error sources, so the density of errors must be sufficiently low in order for logical performance to improve with increasing code size. Here, we report the measurement of logical qubit performance scaling across multiple code sizes, and demonstrate that our system of superconducting qubits has sufficient performance to overcome the additional errors from increasing qubit number. We find our distance-5 surface code logical qubit modestly outperforms an ensemble of distance-3 logical qubits on average, both in terms of logical error probability over 25 cycles and logical error per cycle ($2.914\%\pm 0.016\%$ compared to $3.028\%\pm 0.023\%$). To investigate damaging, low-probability error sources, we run a distance-25 repetition code and observe a $1.7\times10^{-6}$ logical error per round floor set by a single high-energy event ($1.6\times10^{-7}$ when excluding this event). We are able to accurately model our experiment, and from this model we can extract error budgets that highlight the biggest challenges for future systems. These results mark the first experimental demonstration where quantum error correction begins to improve performance with increasing qubit number, illuminating the path to reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references, Fig. S12, Table I

Non-Abelian braiding of graph vertices in a superconducting processor

Indistinguishability of particles is a fundamental principle of quantum mechanics. For all elementary and quasiparticles observed to date - including fermions, bosons, and Abelian anyons - this principle guarantees that the braiding of identical particles leaves the system unchanged. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well developed mathematical description of non-Abelian anyons and numerous theoretical proposals, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. While efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasi-particles, superconducting quantum processors allow for directly manipulating the many-body wavefunction via unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons, we implement a generalized stabilizer code and unitary protocol to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of employing the anyons for quantum computation and utilize braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and - through the future inclusion of error correction to achieve topological protection - could open a path toward fault-tolerant quantum computing

Dalla progettazione all’utilizzo di un sistema informativo geologico al servizio del rilevamento geologico: la banca dati della Regione Lombardia e la cartografia geologica derivata

In questa Tesi è descritto il processo di creazione di un Sistema Informativo Geologico e degli strumenti informatici per la gestione dell’informazione su base geografica, o più semplicemente GIS (Geographic Information System), al servizio delle attività di rilevamento geologico, finalizzato alla raccolta dei dati ed alla loro rappresentazione cartografica nell'ambito di un Sistema Informativo Territoriale (SIT). Un SIT è definibile come l'insieme di uomini, strumenti e procedure che, nell’ambito di una organizzazione, permettono l’acquisizione e la distribuzione dei dati relativi alla conoscenza dei fenomeni e degli attori presenti su territorio; tutto questo è facilitato in gran parte dalle capacità e funzionalità dei GIS. Il Sistema Informativo Territoriale orientato alla Geologia (SIG – Sistema Informativo Geologico) della Regione Lombardia è costituito da un gruppo di lavoro composto da geologi, informatici e geologi-informatici dell’Ente regionale e della società Lombardia Servizi (Gruppo Lombardia Informatica). Ho fatto parte del team di consulenza tecnico-scientifica incaricato da Lombardia Servizi per la realizzazione del SIG regionale. I compiti del gruppo di lavoro sono: - definizione di ruoli e metodi per la costituzione del SIG; - definizione delle logiche per la creazione di strumenti finalizzati all’archiviazione del dato geologico in una banca dati geologica e loro manutenzione; Il progetto è inserito nel più ampio processo di aggiornamento della Cartografia Geologica nazionale (progetto CARG). Il SIG ha come principali obiettivi: - la pianificazione ed esecuzione del rilevamento geologico di dettaglio (scala 1:10.000) del territorio lombardo; - la costruzione di un database della geologia di superficie (ma anche del sottosuolo per le aree di pianura) interrogabile e aggiornabile ; - il supporto ai processi di analisi finalizzati alla descrizione della geologia superficiale e ricostruzione degli eventi che hanno creato il paesaggio attuale; - la rappresentazione cartografica dell’ambiente geologico a partire dal database creato. - la distribuzione dell’informazione geologica archiviata in vari formati (cartaceo e digitale); Sono qui descritte ed analizzate criticamente la filosofia di costruzione delle procedure e le soluzioni tecniche e metodologiche adottate per realizzare gli obiettivi prefissi. L’APAT (Agenzia per la Protezione dell'Ambiente e per i servizi Tecnici nazionali) ha ereditato dal Servizio Geologico il compito di rilevare, aggiornare e pubblicare la Carta Geologica d'Italia (progetto nazionale CARG) quale organo cartografico dello Stato in base alla legge 68/60. Nel 1976 era stato completato il rilevamento della Carta geologica d'Italia alla scala 1:100.000 costituita da 278 fogli a copertura del territorio nazionale; per il suo aggiornamento sono stati definiti strumenti normativi idonei a garantire l'omogeneità dei contenuti e della rappresentazione cartografica; la definizione delle norme discende dall'applicazione di linee guida, frutto dell'attività di Commissioni e Gruppi di lavoro, pubblicate nei Quaderni della serie III (ed. APAT). L’Ente Regione Lombardia, per rispondere all’impegno istituzionale di aggiornamento della Carta Geologica, all’interno del più ampio e strutturato Sistema Informativo Territoriale regionale, ha dunque creato il Sistema Informativo Geologico (SIG) regionale. Il rapido evolversi delle ricerche nel campo delle Scienze della Terra e l'importanza che riveste la cartografia geologica nella gestione del territorio, hanno spinto la Regione Lombardia a progettare un rilevamento geologico di dettaglio per dotarsi di una banca dati geologica dalla quale derivare la propria cartografia geologica (alla scala 1:10.000). Sono stati quindi definiti standard specifici rispondenti a questa esigenza di maggior dettaglio (rispetto a quanto indicato dal progetto nazionale CARG) ed è stato pianificato e in gran parte realizzato un rilevamento ex-novo finalizzato alla pubblicazione del dato alla scala del rilevamento e per la sua generalizzazione alle scale 1:25.000 e 50.000. Alla fine del processo saranno stati realizzati 14 fogli del territorio lombardo relativamente alle aree alpine e di passaggio alla pianura (Bergamo, Bormio, Breno, Clusone, Lecco, Iseo, Malonno, Ponte di Legno, Sondrio, Vimercate, Milano, Bagolino, Seregno, Voghera). In tale progetto sono anche coinvolti le Università di Milano, di Pavia e di Bolona, il Politecnico di Milano e il CNR - Centro di Studio per la Geodinamica Alpina e Quaternaria di Milano. L’attività di rilevamento geologico è di competenza dei funzionari regionali della Struttura Sistema Informativo Territoriale della Direzione Generale Territorio e Urbanistica che, coadiuvati da geologi rilevatori, realizzano tutte le fasi del lavoro, dalla raccolta del dato fino alla sua pubblicazione. L’ambiente informatico GIS sviluppato, denominato CARGeo (Cartografia Geologica), permette di inserire i dati raccolti da geologi rilevatori in un database appositamente predisposto, mediante interfacce grafiche semplificate e procedure standard di archiviazione e controllo di correttezza formale. La banca dati è costruita in modo da facilitare l’archiviazione della maggior parte dei dati che normalmente il geologo registra nella carta e nei taccuini di terreno e, allo stesso tempo, guidarlo nella raccolta organica dell’informazione geologica. Nella strutturazione del database è stata privilegiata la possibilità di inserire attributi direttamente associabili agli elementi geometrici anziché attraverso schede associate a punti di osservazione. Il geologo rilevatore interviene per correggere errori di digitalizzazione o di attribuzione con un processo ciclico, fino ad ottenere una banca dati corretta secondo gli standard predefiniti. Gli strumenti di creazione della banca dati permettono anche di: - disegnare gli schemi accessori (sezioni geologiche, schemi stratigrafici e strutturali etc.); - eseguire lo “sfoltimento” e posizionamento delle annotazioni sulla mappa (sigle di unità litologiche e parametri di inclinazione delle giaciture) secondo criteri di leggibilità della carta - creare le legende; - creare banche dati a scala inferiore (1:25.000 e 50.000); - stampare e pubblicare carte geologiche complete di schemi e legende. Il sistema contiene gli strumenti necessari alla migrazione della banca dati dalla struttura proprietaria CARG-Regione Lombardia a quella CARG-APAT secondo la struttura definita nei Quaderni della serie III Il Sistema nel corso del biennio 2006-2007 ha raggiunto la fase di consegna dei dati (derivazione e generalizzazione della banca dati CARG-APAT 1.50.000 da quella 1:10.000 CARG-Regione Lombardia) dei primi fogli completati (ISEO, MALONNO, LECCO e SONDRIO) con ritardo rispetto alla programmazione. Sono state analizzate le cause che hanno portato a questo rallentamento del flusso di lavoro, quindi apportate le necessarie modifiche al Sistema. Sono qui descritti i problemi e le soluzioni trovate per migliorare l'efficienza del sistema. Attualmente il Sistema Informativo Geologico è in una fase di ristrutturazione, che vede la migrazione verso un’architettura informatica basata sulla piattaforma ARCGis® 9.x. Attraverso il Sistema Informativo Geologico viene tentata una sintesi fra le logiche metodologiche dei due ambiti tecnico-scientifici coinvolti (Geologia e Informatica), in un ambiente dove ricercatori e tecnici lavorano sperimentando l’interazione tra le conoscenze e le metodologie conoscitive tipiche delle Scienze Geologiche e le tecnologie e processi logici delle Scienze Informatiche. Con questa Tesi è documentato tutto il percorso di costruzione della banca dati geologica attraverso e all’interno del sistema realizzato assieme gruppo di lavoro composto da geologi e tecnici informatici, cui ho partecipato, riassumendo gli oltre 9 anni di lavoro dall’ideazione del progetto CARGeo, anche in funzione del suo miglioramento

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19