Effect of spirometry on intra-thoracic pressures

Due to the high intra-thoracic pressures associated with forced vital capacity manoeuvres, spirometry is contraindicated for vulnerable patients. However, the typical pressure response to spirometry has not been reported. Eight healthy, recreationally-active men performed spirometry while oesophageal pressure was recorded using a latex balloon-tipped catheter. Peak oesophageal pressure during inspiration was - 47 ± 9 cmH O (37 ± 10% of maximal inspiratory pressure), while peak oesophageal pressure during forced expiration was 102 ± 34 cmH O (75 ± 17% of maximal expiratory pressure). The deleterious consequences of spirometry might be associated with intra-thoracic pressures that approach maximal values during forced expiration

Low-efficiency long gamma-ray bursts: a case study with AT2020blt

The Zwicky Transient Facility recently announced the detection of an optical transient AT2020blt at redshift z = 2.9, consistent with the afterglow of an on-axis gamma-ray burst. However, no prompt emission was observed. We analyse AT2020blt with detailed models, showing the data are best explained as the afterglow of an on-axis long gamma-ray burst, ruling out other hypotheses such as a cocoon and a low-Lorentz factor jet. We search Fermi data for prompt emission, setting deeper upper limits on the prompt emission than in the original detection paper. Together with KONUS-Wind observations, we show that the gamma-ray efficiency of AT2020blt is 0.3-4.5. We speculate that AT2020blt and AT2021any belong to the low-efficiency tail of long gamma-ray burst distributions that are beginning to be readily observed due to the capabilities of new observatories like the Zwicky Transient Facility

Changes in and predictors of length of stay in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England: a population-based

BACKGROUND Decreases in length of stay (LOS) in hospital after breast cancer surgery can be partly attributed to the change to less radical surgery, but many other factors are operating at the patient, surgeon and hospital levels. This study aimed to describe the changes in and predictors of length of stay (LOS) in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England. METHODS Cases of female invasive breast cancer diagnosed in two English cancer registry regions were linked to Hospital Episode Statistics data for the period 1st April 1997 to 31st March 2005. A subset of records where women underwent mastectomy or breast conserving surgery (BCS) was extracted (n = 44,877). Variations in LOS over the study period were investigated. A multilevel model with patients clustered within surgical teams and NHS Trusts was used to examine associations between LOS and a range of factors. RESULTS Over the study period the proportion of women having a mastectomy reduced from 58% to 52%. The proportion varied from 14% to 80% according to NHS Trust. LOS decreased by 21% from 1997/98 to 2004/05 (LOSratio = 0.79, 95%CI 0.77-0.80). BCS was associated with 33% shorter hospital stays compared to mastectomy (LOSratio = 0.67, 95%CI 0.66-0.68). Older age, advanced disease, presence of comorbidities, lymph node excision and reconstructive surgery were associated with increased LOS. Significant variation remained amongst Trusts and surgical teams. CONCLUSION The number of days spent in hospital after breast cancer surgery has continued to decline for several decades. The change from mastectomy to BCS accounts for only 9% of the overall decrease in LOS. Other explanations include the adoption of new techniques and practices, such as sentinel lymph node biopsy and early discharge. This study has identified wide variation in practice with substantial cost implications for the NHS. Further work is required to explain this variation

Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer

Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.P50 GM067041 - NIGMS NIH HHS; R01 GM099920 - NIGMS NIH HHS; GM-067041 - NIGMS NIH HHS; GM-099920 - NIGMS NIH HH

A critique of the World Resources Institute's report "Pesticides and the immune system: the public health risks".

A recent World Resources Institute (WRI) report concluded that pesticides are a likely cause of immune suppression for millions of people throughout the world. The gravity of this conclusion motivated us to review the scientific evidence cited in the report. The predominant human evidence came from cross-sectional studies conducted in the former Soviet Union.These studies were difficult to evaluate due to incomplete reporting and had obvious limitations in terms of subject selection, exposure assessment,lack of quality control, statistical analysis, adequacy of the comparison group, and confounding. The toxicologic evidence was comprised mainly of acute high-dose studies in which the exposure conditions resulted in systemic toxicity. The relevance of these studies to effects at typical human exposure levels is questionable. We did not find consistent, credible evidence to support the conclusion of widespread pesticide-related immune suppression. Nonetheless, the WRI report is an important document because it focuses attention on a potentially important issue for future research and brings a substantial literature of foreign language studies to the attention of Western scientists

Wean Earlier and Automatically with New technology (the WEAN study): a protocol of a multicentre, pilot randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Weaning is the process during which mechanical ventilation is withdrawn and the work of breathing is transferred from the ventilator back to the patient. Prolonged weaning is associated with development of ventilator-related complications and longer stays in the Intensive Care Unit (ICU). Computerized or Automated Weaning is a novel weaning strategy that continuously measures and adapts ventilator support (by frequently measuring and averaging three breathing parameters) and automatically conducts Spontaneous Breathing Trials to ascertain whether patients can resume autonomous breathing. Automated Weaning holds promise as a strategy to reduce the time spent on the ventilator, decrease ICU length of stay, and improve clinically important outcomes.</p> <p>Methods/Design</p> <p>A pilot weaning randomized controlled trial (RCT) is underway in the ICUs of 8 Canadian hospitals. We will randomize 90 critically ill adults requiring invasive ventilation for at least 24 hours and identified at an early stage of the weaning process to either Automated Weaning (SmartCare™) or Protocolized Weaning. The results of a National Weaning Survey informed the design of the Protocolized Weaning arm. Both weaning protocols are operationalized in Pressure Support mode, include opportunities for Spontaneous Breathing Trials, and share a common sedation protocol, oxygen titration parameters, and extubation and reintubation criteria. The primary outcome of the WEAN study is to evaluate compliance with the proposed weaning and sedation protocols. A key secondary outcome of the pilot RCT is to evaluate clinician acceptance of the weaning and sedation protocols. Prior to initiating the WEAN Study, we conducted a run-in phase, involving two patients per centre (randomizing the first participant to either weaning strategy and assigning the second patient to the alternate strategy) to ensure that participating centres could implement the weaning and sedation protocols and complete the detailed case report forms.</p> <p>Discussion</p> <p>Mechanical ventilation studies are difficult to implement; requiring protocols to be operationalized continuously and entailing detailed daily data collection. As the first multicentre weaning RCT in Canada, the WEAN Study seeks to determine the feasibility of conducting a large scale future weaning trial and to establish a collaborative network of ICU clinicians dedicated to advancing the science of weaning.</p> <p>Trial Registration Number</p> <p>ISRCTN43760151</p

The role of an extended medial column arthrodesis for Charcot midfoot neuroarthropathy

The etiology of diabetic Charcot neuroarthropathy involving the midfoot often includes an inciting traumatic event or repetitive micro-trauma from an uncompensated biomechanical imbalance that potentiates an incompletely understood pathway leading to a rocker-bottom foot deformity and ulceration. In the setting of a severe Charcot foot fracture and/or dislocation with obvious osseous instability, diagnostic delay can potentiate the limb-threatening sequelae of infected midfoot ulcerations in this patient population. In this article, the authors discuss the thought process as well as the advantages of performing an extended medial column arthrodesis for selected Charcot midfoot deformities

Compressed collagen and decellularized tissue: novel components in a pipeline approach for the study of cancer metastasis

Metastasis is a complex process which is difficult to study and model. Experimental ingenuity is therefore essential when seeking to elucidate the biological mechanisms involved. Typically, in vitro models of metastasis have been overly simplistic, lacking the characteristic elements of the tumour microenvironment, whereas in vivo models are expensive, requiring specialist resources. Here we propose a pipeline approach for the study of cell migration and colonization, two critical steps in the metastatic cascade.We used a range of extracellular matrix derived contexts to facilitate a progressive approach to the observation and quantification of cell behaviour in 2D, 3D and at border zones between dimensions. At the simplest level, cells were set onto collagen-coated plastic or encapsulated within a collagen matrix. To enhance this, a collagen compression technique provided a stiffened, denser substrate which could be used as a 2D surface or to encapsulate cells. Decellularized tissue from the chorioallantoic membrane of the developing chicken embryo was used to provide a more structured, biologically relevant extracellular matrix-based context in which cell behaviour could then be compared with its in vivo counterpart.Cell behaviour could be observed and quantified within each context using standard laboratory techniques of microscopy and immunostaining, affording the opportunity for comparison and contrast of behaviour across the whole range of contexts. In particular, the temporal constraints of the in vivo CAM were removed when cells were cultured on the decellularized CAM, allowing for much longer-term cell colonization and cell-cell interaction.Together the assays within this pipeline provide the opportunity for the study of cell behaviour in a replicable way across multiple environments. The assays can be set up and analysed using easily available resources and standard laboratory equipment. We believe this offers the potential for the detailed study of cell migration and colonization of tissue, essential steps in the metastatic cascade. Also, we propose that the pipeline could be used in the wider arena of cell culture in general with the increasingly more complex contexts allowing cell behaviours and interactions to be explored in a stepwise fashion in an integrated way