Measurement of Magnetic Cavitation Driven by Heat Flow in a Plasma.

We describe the direct measurement of the expulsion of a magnetic field from a plasma driven by heat flow. Using a laser to heat a column of gas within an applied magnetic field, we isolate Nernst advection and show how it changes the field over a nanosecond timescale. Reconstruction of the magnetic field map from proton radiographs demonstrates that the field is advected by heat flow in advance of the plasma expansion with a velocity v_{N}=(6±2)×10^{5} m/s. Kinetic and extended magnetohydrodynamic simulations agree well in this regime due to the buildup of a magnetic transport barrier.

Percentage of intrathoracic stomach predicts operative and post-operative morbidity, persistent reflux and PPI requirement following laparoscopic hiatus hernia repair and fundoplication.

PURPOSE: Large hiatus hernias are relatively common and can be associated with adverse symptoms and serious complications. Operative repair is indicated in this patient group for symptom management and the prevention of morbidity. This study aimed to identify predictors of poor outcomes following laparoscopic hiatus hernia repair and fundoplication (LHHRaF) to aid in counselling potential surgical candidates. METHODOLOGY: A retrospective analysis was performed from a prospectively maintained, multicentre database of patients who underwent LHHRaF between 2014 and 2020. Revision procedures were excluded. Hernia size was defined as the intraoperative percentage of intrathoracic stomach, estimated by the surgeon to the nearest 10%. Predictors of outcomes were determined using a prespecified multivariate logistic regression model. RESULTS: 625 patients underwent LHHRaF between 2014 and 2020 with 443 patients included. Median age was 65 years, 62.9% were female and 42.7% of patients had ≥ 50% intrathoracic stomach. In a multivariate regression model, intrathoracic stomach percentage was predictive of operative complications (P = 0.014, OR 1.05), post-operative complications (P = 0.026, OR 1.01) and higher comprehensive complication index score (P = 0.023, OR 1.04). At 12 months it was predictive of failure to improve symptomatic reflux (P = 0.008, OR 1.02) and persistent PPI requirement (P = 0.047, OR 1.02). Operative duration and blood loss were predicted by BMI (P = 0.004 and < 0.001), Type III/IV hernias (P = 0.045 and P = 0.005) and intrathoracic stomach percentage (P = 0.009 and P < 0.001). Post-operative length of stay was predicted by age (P < 0.001) and emergency presentation (P = 0.003). CONCLUSION: In a multivariate regression model, intrathoracic stomach percentage was predictive of operative and post-operative morbidity, PPI use, and failure to improve reflux symptoms at 12 months.

A standardized approach for the thoracic dissection in robotic-assisted minimally invasive esophagectomy (RAMIE).

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being adopted as the preferred surgical treatment for esophageal cancer, as it is superior to open esophagectomy and a good alternative to conventional minimally invasive esophagectomy. This paper addresses the technical details of the thoracoscopic phase of RAMIE, including the operating room set-up, patient positioning, port placement, and surgical steps.

Involvement and alteration of the Sonic Hedgehog pathway is associated with decreased cholesterol level in trisomy 18 and SLO amniocytes.

BACKGROUND: Trisomy 18 and Smith-Lemli-Opitz syndrome are two polymalformative conditions in which a cholesterol defect has been noted. When they occur prenatally, they are associated with a decreased maternal unconjugated estriol (uE(3)) level. Cholesterol plays an essential role in the Sonic Hedgehog pathway, allowing Shh protein maturation leading to its maximal activity. Many malformations in these two syndromes occur in Shh dependent tissues. We thus sought to assess whether a cholesterol defect could affect the Shh pathway and explain some of the observed malformations. MATERIALS AND METHODS: We selected 14 cases of trisomy 18 and 3 cases of SLO in which the maternal uE(3) level was decreased and reported malformations were observed after fetopathological examination. We correlated the number of malformations with maternal uE(3) level. We then carried out cholesterol concentrations in separate culture media consisting of trisomy 18, SLO and control amniocytes. Finally, we analyzed the Shh pathway by testing the gene expression of several Shh components: GLI transcription factors, BMP2, BMP4, TGFß1, COL1A1 and COL1A2. RESULTS AND DISCUSSION: There was an inverse correlation between phenotypic severity and maternal uE(3) levels in SLO and trisomy 18. The cholesterol levels in the amniocyte culture media were correlated with maternal uE3 levels and were significantly lower in T18 and SLO amniocytes, reflecting cholesterol defects. There was an alteration in the Shh pathway since expression of several genes was decreased in T18 and SLO amniocytes. However, these cholesterol defects were not solely responsible for the altered Shh pathway and the malformations observed.

Conditioning out-of-date bank-stored red blood cells using a cell-saver auto-transfusion device: effects on numbers of red cells and quality of suspension fluid.

We investigated the utility of a cell-saver device for processing out-of-date red blood cells, by washing twenty bags of red blood cells that had been stored for between 36 and 55 days. The volume of recovered cells, and the characteristics of the suspension fluid, were measured before and after treatment. The ratio of free haemoglobin to total haemoglobin was up to 0.02 before processing, and up to 0.011 afterwards, changing by between -0.013 and +0.003. This ratio met the current standard for free haemoglobin (less than 0.008 in more than 75% of samples), both before and after processing. Ninety-three percent of red blood cells survived the process. Potassium ion concentration fell from above 15 mmol.l(-1) in all cases, to a mean of 6.4 mmol.l(-1) (p < 0.001). The pH rose to a mean value of 6.44 (p = 0.001). Lactate ion concentration fell to a mean value of 14 mmol.l(-1) (p < 0.001). Sodium ion concentration rose from a mean value of 93 mmol.l(-1) to a mean value of 140 mmol.l(-1) (p < 0.001). A useful proportion of out-of-date red blood cells remained intact after conditioning using a cell-saver, and the process lowered concentrations of potentially toxic solutes in the fluid in which they were suspended.

International Standards for Neurological Classification of Spinal Cord Injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

International standards for neurological classification of spinal cord injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

The Walking Index for Spinal Cord Injury (WISCI/WISCI II): nature, metric properties, use and misuse.

STUDY DESIGN: Literature review. OBJECTIVE: To critically review all publications/internet sites that have described/used the Walking Index for Spinal Cord Injury (WISCI II), as a measure of impairment of walking function after spinal cord injury (SCI), in order to identify its psychometric properties, clarify its nature, specify misuse and incorporate the findings in an updated guide. METHOD: A systematic literature search was done of Ovid MEDLINE, CINAHL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and electronic sites using key words: WISCI or WISCI II, SCI, paraplegia/ tetraplegia/ quadriplegia and ambulation/gait/walking. Among 1235 citations retrieved, 154 relevant articles/sites were identified, classified and examined by the authors; recommendations were made based on findings. RESULTS AND DISCUSSION: The validity (face/concurrent/content/construct/convergent/criterion) and reliability of the WISCI II has been documented in clinical trials and clinical series, and considered adequate by systematic reviewers. In chronic SCI subjects, reliable determination of the maximum (as opposed to self-selected) WISCI II level requires more time and experience by the assessor. The correct use of WISCI II is clarified for testing acute/chronic phases of recovery after SCI, age of subjects, devices and settings. The WISCI II and walking speed measures may be performed simultaneously. CONCLUSION: The increased use of the WISCI II is attributed to its unique characteristics as a capacity measure of walking function and its strong metric properties. Appropriate use of the WISCI II was clarified and incorporated into a new guide for its use. Combining it with a walking speed measure needs further study.

Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.

Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal model at levels that would have a therapeutic effect in humans (up to 70 ng/ml, adequate to achieve phenotypic correction, in an animal injected with 8.5x10(12) vector particles/kg). The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time. In contrast to other viral gene delivery systems, this minimally invasive procedure, consisting of a series of percutaneous intramuscular injections at a single timepoint, was not associated with local or systemic toxicity. Efficient gene transfer to muscle was shown by immunofluorescence staining and DNA analysis of biopsied tissue. Immune responses against factor IX were either absent or transient. These data provide strong support for the feasibility of the approach for therapy of human subjects.

Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors.

Hemophilia B, or factor IX deficiency, is an X-linked recessive disorder occurring in about 1 in 25,000 males. Affected individuals are at risk for spontaneous bleeding into many organs; treatment mainly consists of the transfusion of clotting factor concentrates prepared from human blood or recombinant sources after bleeding has started. Small- and large-animal models have been developed and/or characterized that closely mimic the human disease state. As a preclinical model for gene therapy, recombinant adeno-associated viral vectors containing the human or canine factor IX cDNAs were infused into the livers of murine and canine models of hemophilia B, respectively. There was no associated toxicity with infusion in either animal model. Constitutive expression of factor IX was observed, which resulted in the correction of the bleeding disorder over a period of over 17 months in mice. Mice with a steady-state concentration of 25% of the normal human level of factor IX had normal coagulation. In hemophilic dogs, a dose of rAAV that was approximately 1/10 per body weight that given to mice resulted in 1% of normal canine factor IX levels, the absence of inhibitors, and a sustained partial correction of the coagulation defect for at least 8 months.

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

Observations of pressure anisotropy effects within semi-collisional magnetized plasma bubbles.

Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region. These fields are mapped using time-resolved proton probing in multiple directions. Various experimental, modelling and analytical techniques demonstrate the importance of anisotropic pressure in semi-collisional, high-ß plasmas, causing a reduction in the magnitude of the reconnecting fields when compared to resistive processes. Anisotropic pressure dynamics are crucial in collisionless plasmas, but are often neglected in collisional plasmas. We show pressure anisotropy to be essential in maintaining the interaction layer, redistributing magnetic fields even for semi-collisional, high energy density physics (HEDP) regimes.

NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial activation.

Structural analysis of the promoters of several endothelial genes induced at sites of inflammatory or immune responses reveals binding sites for the transcription factor nuclear factor kappa B (NF-kappa B). Endothelial cells express transcripts encoding the p50/p105 and p65 components of NF-kappa B and the rel-related proto-oncogene c-rel; steady state levels of these transcripts are transiently increased by tumor necrosis factor alpha (TNF-alpha). Western blotting revealed that stimulation of endothelial cells with TNF-alpha resulted in nuclear accumulation of the p50 and p65 components of NF-kappa B. Ultraviolet crosslinking and immunoprecipitation demonstrated binding of the p50 and p65 components of NF-kappa B to the E-selectin kappa B site. Endothelial cells express an inhibitor of NF-kappa B activation, I kappa B-alpha (MAD-3). Protein levels of this inhibitor fall rapidly after TNF-alpha stimulation. In parallel, p50 and p65 accumulate in the nucleus and RNA transcript levels for I kappa B-alpha are dramatically upregulated. Recombinant p65 stimulates expression of E-selectin promoter-reporter constructs. I kappa B-alpha inhibits p65 or TNF-alpha-stimulated E-selectin promoter-reporter gene expression in transfected endothelial cells. The NF-kappa B and I kappa B-alpha system may be an inducible regulatory mechanism in endothelial activation.

Widespread omnivory and low temporal and spatial variation in the diet of fishes in a hydrologically variable northern Australian river.

This article examines the trophic ecology of freshwater fishes (22 species in 15 families) in a wet and dry tropical Australian river of high intra-annual and interannual hydrological variability. Seven major trophic groups were identified by cluster analysis; however, four food items (filamentous algae, chironomid larvae, Trichoptera larvae and Ephemeroptera nymphs) comprised almost half of the average diet of all species. The influence of species, fish size, spatial effects and temporal effects on food use was investigated using redundancy analysis. Size, time and space accounted for little of the perceived variation. Ontogenetic changes in diet were minor and limited to a few large species. Spatial variation in trophic composition of the fish assemblages reflected the effects of the Burdekin Falls and dam, a major geographic barrier, on species distributions. Little spatial variation in diet was detected after accounting for this biogeographical effect. Temporal variations in flow, although marked, had little effect on variations in fish diet composition due to the low temporal diversity of food resources in physically monotonous sand and gravel channels. Species identity accounted for<50% of the observed variation in food choice; omnivory and generalism were pronounced. The aquatic food web of the Burdekin River appears simple, supported largely by autochthonous production (filamentous and benthic microalgae, and to some extent, aquatic macrophytes). Allochthonous food resources appear to be unimportant. The generalist feeding strategies, widespread omnivory and absence of pronounced trophic segregation reported here for Burdekin River fishes may be common to variable and intermittent rivers of subtropical and tropical northern Australia with similar fish communities and may be a general feature of rivers of low habitat diversity and characterized by flow regimes that vary greatly both within and between years.

In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs.

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs.

This study investigated the pharmacokinetics of a human-labeled oral morphine formulation consisting of both immediate and extended release components in dogs. In a randomized design, 14 dogs were administered either 1 or 2 mg/kg morphine orally. Blood samples were collected up to 24 h post drug administration. Plasma concentrations of morphine were measured using high-pressure liquid chromatography with electrochemical coulometric detection. For both groups, maximal concentration occurred at 3 h post drug administration followed by a gradual decrease in morphine concentration over 24 h. There was substantial variability in morphine concentrations among dogs. The higher dose group produced a greater exposure (higher area-under-the-curve), higher peak concentration, longer half-life and a shorter time to peak concentration (t(max)). The specific oral morphine formulation used in this study produced sustained plasma morphine concentrations over 24 h compared with previous intravenous dosing and immediate-release oral morphine studies. However, the low morphine plasma concentrations and high variability produced from this formulation, suggest that the clinical application of this formulation at the doses evaluated in this study are limited.

Review: optical micrometer resolution scanning for non-invasive grading of precancer in the human uterine cervix.

Management of cervical precancer is archetypal for other cancer prevention programmes but has to consider diagnostic and logistic challenges. Numerous optical tools are emerging for non-destructive near real-time early diagnosis of precancerous lesions of the cervix. Non-destructive, real-time imaging modalities have reached pre-commercial status, but high resolution mapping tools are not yet introduced in clinical settings. The NCBI PubMed web page was searched using the keywords 'CIN diagnosis' and the combinations of 'cervix {confocal, optical coherence tomography, ftir, infrared, Raman, vibrational, spectroscopy}'. Suitable titles were identified and their relevant references followed. Challenges in precancer management are discussed. The following tools capable of non-destructive high resolution mapping in a clinical environment were selected: confocal microscopy, optical coherence tomography, IR spectroscopy, and Raman spectroscopy. Findings on the clinical performance of these techniques are put into context in order to assist the reader in judging the likely performance of these methods as diagnostic tools. Rationale for carrying out research under the prospect of the HPV vaccine is given.

[Acetaminophen induced 5-oxoproline acidosis: An uncommon case of high anion gap metabolic acidosis]. / Acidose à la 5-oxoproline induite par le paracétamol : une cause rare d'acidose métabolique à trou anionique augmenté.

The most common causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis, and intoxications. Nevertheless, clinicians can be faced with unexplained HAGMA, with a need to look for less common etiologies. We describe a case of 5-oxoproline (pyroglutamate) acidosis due to chronic acetaminophen ingestion at therapeutic dose in a 79-year-old inpatient. The pathophysiology of this condition is detailed, with abnormalities in the gamma-glutamyl cycle due to acetaminophen ingestion and severe chronic morbidities, resulting in glutathione and cysteine deficiency and then accumulation of 5-oxoproline. In HAGMA, when usual causes have been excluded, 5-oxoproline acidosis should be suspected in patients with chronic morbidities and acetaminophen ingestion. This diagnosis should be kept in mind because it generally resolves quickly with cessation of acetaminophen and administration of intravenous fluids.