The microscale evolution of the erosion front of blood clots exposed to ultrasound stimulated microbubbles

Serial two-photonmicroscopy of blood clots with fluorescently tagged fibrin networks was conducted during microbubble-mediated sonothrombolysis to examine the microscale evolution of the resulting erosion front. The development of a complex zonal erosion pattern was observed, comprised of a cell depleted layer of fibrin network overlying intact clot which then underwent progressive recession. The fibrin zone architecture was dependent on exposure conditions with 0.1 MPa causing no erosion, 0.39 MPa resulting in homogenous structure, and combination 0.39/0.96 MPa pulses forming large-scale tunnels. High speed imaging and Coulter counter data indicated the fibrin zone formation process involves the ejection of intact erythrocytes.

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Stopping guidelines for an effectiveness trial: what should the protocol specify?

Despite long-standing problems in decisions to stop clinical trials, stopping guidelines are often vague or unspecified in the trial protocol. Clear, well-conceived guidelines are especially important to assis...

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What Would You Do? A co-worker despises, calls EMS patients derogatory names

Dr. David Tan and paramedic Steve Whitehead discuss a complex scenario regarding paramedics who despise certain patients and use derogatory terms to refer to those patients. The discussion covers symptoms of burnout and recognizing that EMS serves and cares for others. After watching the discussion share your thoughts on this scenario in the comments and read this article about recognizing and treating your own burnout.

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Remember 2 Things: Altered mental status in geriatric patients

EMS providers frequently assess geriatric patients with altered mental status. This EMS1 training video reviews two common conditions - hypoglycemia and sepsis - that can cause changes in a patient's mental status. After watching Steve Whitehead discuss these conditions learn more about sepsis assessment and treatment in articles from Kelly Grayson (How capnography can be used to identify sepsis) and Rom Duckworth (Sepsis 3.0: implications for paramedics and prehospital care). Then share your geriatric assessment tips in the comments.

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Ecological analyses of the associations between injury risk and socioeconomic status, geography and Aboriginal ethnicity in British Columbia, Canada

The current study examines what factors contribute to higher injury risk among Aboriginal peoples, compared to the total British Columbia (BC) population. We explore socioeconomic, geographic, and cultural fac...

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Validation of a rapid one-step high sensitivity real-time quantitative PCR system for detecting major BCR-ABL1 mRNA on an International Scale

Detection and quantitation of BCR-ABL1 transcripts are crucial for managing patients with chronic myeloid leukemia (CML). Although real-time quantitative polymerase chain reaction (RT-qPCR) can be measured on an ...

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Novel pre-treatment of zeolite materials for the removal of sodium ions: potential materials for coal seam gas co-produced wastewater

Coal seam gas (CSG) is the extraction of methane gas that is desorbed from the coal seam and brought to the surface using a dewatering and depressurisation process within the saturated coalbed. The extracted w...

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Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10

Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of

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The EMS calls that make me sad, frustrated and vulnerable

By Susie Crosby

We had a difficult call today. You know I can't go into details, but I can tell you that it wasn't easy and it hit me hard.

Being part of an ambulance crew can put some pretty unpleasant things into view. I've seen trauma ... "blood n' guts" ... and death.

I've honestly been surprised by my whole reaction to it all ... or lack of reaction. Sometimes it actually bothers me that I'm not bothered by it more.

While I do have a rather strong stomach and I am a bit of a trauma/training junkie I just chalked it up to a sort of disconnect for the purpose of self-preservation. It's an ability to do my job in controlled chaos.

Sometimes the hardest calls aren't the ones we might think. One particular call that stuck with me didn't end in death and didn't involve any gore. But it was an event that would change a young life forever. It's the one I think about that tears at my heart the most.

So I've come to the conclusion that it's the human element that gets me. It's doing everything I can, bringing all the different aspects of my training together, performing to the best of my ability and I still can't direct the outcome.

Those calls make me sad. They frustrate me and they make me feel vulnerable.

My first response isn't to walk away feeling proud that I've done all I could. It's to walk away thinking of any possible way I could have done better.

While it's not a warm and fuzzy feeling, it is a necessary feeling, and one that hopefully will benefit the next patient and make the next call go more smoothly.

I believe the Good Lord makes the ultimate decision as to which patient makes it and which doesn't. He also gives us the skills and the privilege to make the process a little easier.

About the author
Susie George is an EMT-Intermediate in rural Oregon, mother of seven and lives on a small hobby farm. 

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EMS Artwork: Calm torment

We recently worked a cardiac arrest where a woman collapsed while enjoying a dinner her husband of 50 years prepared for her. When we arrived, he was doing CPR on her in the middle of the kitchen floor while following the instructions given to him on the phone by the dispatcher. Other family members were in the living room in a state of unbelief and worry, they greeted us with such relief. People seem to think when we arrive we're going to save the day and everything will be OK.

Read more about this image here.

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Remember 2 Things: Stroke mimics

Several conditions mimic or look like stroke. Remember the two things - hypogylcemia and seizures - that can often look like stroke in this EMS1 training video from Steve Whitehead. After watching share your experience with stroke scales in the comments, watch another episode of Remember 2 Things on improving stroke recognition and response, and read more about stroke assessment scales.

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Computational cell analysis for label-free detection of cell properties in a microfluidic laminar flow

Analyst, 2016, Advance Article
DOI: 10.1039/C6AN00295A, Paper

Alex Ce Zhang, Yi Gu, Yuanyuan Han, Zhe Mei, Yu-Jui Chiu, Lina Geng, Sung Hwan Cho, Yu-Hwa Lo
This method utilizes machine learning algorithms and fluid mechanic properties of cells in a microfluidic channel to find the compositions of cell mixtures.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry

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Acute renal infarction resulting from fibromuscular dysplasia: a case report

Acute abdominal pain is one of the most frequent complaints evaluated at emergency departments. Approximately 25 % of abdominal pain patients discharged from emergency departments are diagnosed with undifferen...

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Changes in the survival of older patients with hematologic malignancies in the early 21st century

BACKGROUND

Survival for patients with hematologic malignancies has improved during the early 21st century. However, it is unclear whether older patients have benefited to the same extent as younger patients. This study examines changes in survival for older patients with the 7 most common hematologic malignancies.

METHODS

Period analysis was used to examine survival for patients who were 65 years old or older and were diagnosed with a common hematologic malignancy between 1992 and 2012 with data from the Surveillance, Epidemiology, and End Results database.

RESULTS

Five-year relative survival increased for older patients with hematologic malignancies with the partial exception of acute myelogenous leukemia, for which no change in survival was seen for patients who were 75 years old or older. Patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma, including the oldest patients, had especially strong improvements, with increases in 5-year relative survival for patients who were 85 years old or older of 31.5% and 39.6%, respectively, between 1997-2000 and 2009-2012.

CONCLUSIONS

Despite these increases, survival rates did not reach those observed for patients aged 50 to 59 years for any hematologic malignancy. Newer therapies and a better understanding of how to treat older patients have led to increased survival expectations for older patients with most hematologic malignancies, but an age-related survival disparity persists. Cancer 2016. © 2016 American Cancer Society.

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Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E1508)

BACKGROUND

Preclinical targeting of the hedgehog pathway by vismodegib and of insulin-like growth factor 1 receptor by cixutumumab enhances the efficacy of chemotherapy and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in small cell lung cancer.

METHODS

Patients with newly diagnosed extensive-stage small cell lung cancer (SCLC-ED) were randomized to receive four 21-day cycles of cisplatin and etoposide alone (cisplatin at 75 mg/m² on day 1 and etoposide at 100 mg/m² on days 1-3; arm A) or in combination with either vismodegib (150 mg/d by mouth; arm B) or cixutumumab (6 mg/kg/wk intravenously on day 1; arm C). The primary endpoint was progression-free survival (PFS). Circulating tumor cells (CTCs) were isolated/enumerated with the Veridex CellSearch platform at the baseline.

RESULTS

One hundred fifty-two eligible patients were treated. Patient demographics and disease characteristics were well balanced between the 3 arms except for the higher rate with a performance status of 0 in arm B (P = .03). The median PFS times in arms A, B, and C were 4.4, 4.4, and 4.6 months, respectively; the median overall survival (OS) times were 8.8, 9.8, and 10.1 months, respectively; and the response rates were 48%, 56%, and 50%, respectively. None of the comparisons of these outcomes were statistically significant. The median OS was 10.5 months for those with low CTC counts (≤100/7.5 mL) at baseline and 7.2 months for those with high CTC counts (hazard ratio, 1.74; P = .006).

CONCLUSIONS

There was no significant improvement in PFS or OS with the addition of either vismodegib or cixutumumab to chemotherapy in patients with SCLC-ED. A low baseline CTC count was associated with a favorable prognosis. Cancer 2016. © 2016 American Cancer Society.

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Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial

BACKGROUND

Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment.

METHODS

A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations.

RESULTS

There were significant associations of genetic polymorphisms in steroid 5α-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; P_trend = .03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; P_trend = .01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; P_trend < .05) consistently and significantly altered all androgen concentrations. Several SNPs (SRD5A1 rs3822430, SRD5A2 rs2300700, CYP3A43 rs800672, and CYP19 rs700519; P_trend < .05) were significantly associated with both circulating hormone levels and prostate cancer risk.

CONCLUSIONS

Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted. Cancer 2016. © 2016 American Cancer Society.

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Understanding the value of cancer drugs–the devil is in the detail

New tools to assess the value of cancer drugs are not sufficiently detailed. Economic modeling provides the ideal method with which to assess their value.

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IJMS, Vol. 17, Pages 694: Global Metabolic Regulation of the Snow Alga Chlamydomonas nivalis in Response to Nitrate or Phosphate Deprivation by a Metabolome Profile Analysis

In the present work, Chlamydomonas nivalis, a model species of snow algae, was used to illustrate the metabolic regulation mechanism of microalgae under nutrient deprivation stress. The seed culture was inoculated into the medium without nitrate or phosphate to reveal the cell responses by a metabolome profile analysis using gas chromatography time-of-flight mass spectrometry (GC/TOF-MS). One hundred and seventy-one of the identified metabolites clustered into five groups by the orthogonal partial least squares discriminant analysis (OPLS-DA) model. Among them, thirty of the metabolites in the nitrate-deprived group and thirty-nine of the metabolites in the phosphate-deprived group were selected and identified as "responding biomarkers" by this metabolomic approach. A significant change in the abundance of biomarkers indicated that the enhanced biosynthesis of carbohydrates and fatty acids coupled with the decreased biosynthesis of amino acids, N-compounds and organic acids in all the stress groups. The up- or down-regulation of these biomarkers in the metabolic network provides new insights into the global metabolic regulation and internal relationships within amino acid and fatty acid synthesis, glycolysis, the tricarboxylic acid cycle (TCA) and the Calvin cycle in the snow alga under nitrate or phosphate deprivation stress.

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IJMS, Vol. 17, Pages 696: Identification of More Feasible MicroRNA–mRNA Interactions within Multiple Cancers Using Principal Component Analysis Based Unsupervised Feature Extraction

MicroRNA(miRNA)–mRNA interactions are important for understanding many biological processes, including development, differentiation and disease progression, but their identification is highly context-dependent. When computationally derived from sequence information alone, the identification should be verified by integrated analyses of mRNA and miRNA expression. The drawback of this strategy is the vast number of identified interactions, which prevents an experimental or detailed investigation of each pair. In this paper, we overcome this difficulty by the recently proposed principal component analysis (PCA)-based unsupervised feature extraction (FE), which reduces the number of identified miRNA–mRNA interactions that properly discriminate between patients and healthy controls without losing biological feasibility. The approach is applied to six cancers: hepatocellular carcinoma, non-small cell lung cancer, esophageal squamous cell carcinoma, prostate cancer, colorectal/colon cancer and breast cancer. In PCA-based unsupervised FE, the significance does not depend on the number of samples (as in the standard case) but on the number of features, which approximates the number of miRNAs/mRNAs. To our knowledge, we have newly identified miRNA–mRNA interactions in multiple cancers based on a single common (universal) criterion. Moreover, the number of identified interactions was sufficiently small to be sequentially curated by literature searches.

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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

Thrombolytic therapy with intravenous alteplase (recombinant tissue-type plasminogen activator) at a dose of 0.9 mg per kilogram of body weight is an effective treatment for acute ischemic stroke, despite increasing the risk of intracerebral hemorrhage. However, the Japanese drug safety authority…

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Finding the Right t-PA Dose for Asians with Acute Ischemic Stroke

The efficacy of intravenous thrombolysis with tissue plasminogen activator (t-PA) for improving outcomes in patients with acute ischemic stroke has driven the infrastructure development for acute stroke care delivery in the United States, Europe, and Australia for the past 20 years. The early…

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Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack

Ischemic stroke and transient ischemic attack are common, and the risk of subsequent ischemic events is particularly high during the first 90 days after the index cerebrovascular event. Aspirin at a dose of 50 to 325 mg daily is commonly used in this context. However, the benefit of aspirin in the…

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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

Thrombolytic therapy with intravenous alteplase (recombinant tissue-type plasminogen activator) at a dose of 0.9 mg per kilogram of body weight is an effective treatment for acute ischemic stroke, despite increasing the risk of intracerebral hemorrhage. However, the Japanese drug safety authority…

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Composition and genomic organization of arthropod Hox clusters

Background: The ancestral arthropod is believed to have had a clustered arrangement of ten Hox genes. Within arthropods, Hox gene mutations result in transformation of segment identities. Despite the fact that variation in segment number/character was common in the diversification of arthropods, few examples of Hox gene gains/losses have been correlated with morphological evolution. Furthermore, a full appreciation of the variation in the genomic arrangement of Hox genes in extant arthropods has not been recognized, as genome sequences from each major arthropod clade have not been reported until recently. Initial genomic analysis of the chelicerate Tetranychus urticae suggested that loss of Hox genes and Hox gene clustering might be more common than previously assumed. To further characterize the genomic evolution of arthropod Hox genes, we compared the genomic arrangement and general characteristics of Hox genes from representative taxa from each arthropod subphylum. Results: In agreement with others, we find arthropods generally contain ten Hox genes arranged in a common orientation in the genome, with an increasing number of sampled species missing either Hox3 or abdominal-A orthologs. The genomic clustering of Hox genes in species we surveyed varies significantly, ranging from 0.3 to 13.6 Mb. In all species sampled, arthropod Hox genes are dispersed in the genome relative to the vertebrate Mus musculus. Differences in Hox cluster size arise from variation in the number of intervening genes, intergenic spacing, and the size of introns and UTRs. In the arthropods surveyed, Hox gene duplications are rare and four microRNAs are, in general, conserved in similar genomic positions relative to the Hox genes. Conclusions: The tightly clustered Hox complexes found in the vertebrates are not evident within arthropods, and differential patterns of Hox gene dispersion are found throughout the arthropods. The comparative genomic data continue to support an ancestral arthropod Hox cluster of ten genes with a shared orientation, with four Hox gene-associated miRNAs, although the degree of dispersion between genes in an ancestral cluster remains uncertain. Hox3 and abdominal-A orthologs have been lost in multiple, independent lineages, and current data support a model in which inversions of the Abdominal-B locus that result in the loss of abdominal-A correlate with reduced trunk segmentation.

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Exploration of the Drosophila buzzatii transposable element content suggests underestimation of repeats in Drosophila genomes

Background: Many new Drosophila genomes have been sequenced in recent years using new-generation sequencing platforms and assembly methods. Transposable elements (TEs), being repetitive sequences, are often misassembled, especially in the genomes sequenced with short reads. Consequently, the mobile fraction of many of the new genomes has not been analyzed in detail or compared with that of other genomes sequenced with different methods, which could shed light into the understanding of genome and TE evolution. Here we compare the TE content of three genomes: D. buzzatii st-1, j-19, and D. mojavensis. Results: We have sequenced a new D. buzzatii genome (j-19) that complements the D. buzzatii reference genome (st-1) already published, and compared their TE contents with that of D. mojavensis. We found an underestimation of TE sequences in Drosophila genus NGS-genomes when compared to Sanger-genomes. To be able to compare genomes sequenced with different technologies, we developed a coverage-based method and applied it to the D. buzzatii st-1 and j-19 genome. Between 10.85 and 11.16 % of the D. buzzatii st-1 genome is made up of TEs, between 7 and 7,5 % of D. buzzatii j-19 genome, while TEs represent 15.35 % of the D. mojavensis genome. Helitrons are the most abundant order in the three genomes. Conclusions: TEs in D. buzzatii are less abundant than in D. mojavensis, as expected according to the genome size and TE content positive correlation. However, TEs alone do not explain the genome size difference. TEs accumulate in the dot chromosomes and proximal regions of D. buzzatii and D. mojavensis chromosomes. We also report a significantly higher TE density in D. buzzatii and D. mojavensis X chromosomes, which is not expected under the current models. Our easy-to-use correction method allowed us to identify recently active families in D. buzzatii st-1 belonging to the LTR-retrotransposon superfamily Gypsy.

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Ecological analyses of the associations between injury risk and socioeconomic status, geography and Aboriginal ethnicity in British Columbia, Canada

Background: The current study examines what factors contribute to higher injury risk among Aboriginal peoples, compared to the total British Columbia (BC) population. We explore socioeconomic, geographic, and cultural factors, and combinations of these factors, that contribute to increased injury risk for Aboriginal peoples. This follows from our previously reported findings of improvements in injury risk over time for both the total and Aboriginal populations.Data and methodsWe use provincial population-based linked health care databases of hospital discharge records. We identify three population groups: total BC population, and Aboriginal populations living off-reserve, or on-reserve. For each group we calculate age and gender-standardized relative risks (SRR) of injury-related hospitalization, relative to the total population of BC, for two 5-year time periods (1999–2003, and 2004–2008). We use custom data from the 2001 and 2006 long-form Censuses that described income, education, employment, housing conditions, proportion of urban dwellers, proportion of rural dwellers, and prevalence of Aboriginal ethnicity. We use multivariable linear regression to examine the associations between the census characteristics and SRR of injury. Results: The best-fitting model was an excellent fit (R 2  = 0.905, p < 0.001) among the three population groups within Health Service Delivery Areas of BC. We find indicators in all three categories (socioeconomic, geographic, and cultural) are associated with disparity in injury risk. While the socioeconomic indicators (income, education, housing, employment) were shown to be highly correlated, only living in housing that needs major repair and occupational hazardousness, along with rural residence and Aboriginal ethnicity, remained in the final model. Our data show that cultural density is not associated with injury risk for Aboriginal peoples, and that living off-reserve is associated with reduced injury by improving socioeconomic and geographic conditions (compared to living on-reserve). Finally, our analyses show that Aboriginal status itself is associated with injury risk. Conclusions: Our findings confirm previous research indicating that geographical differences differentiate injury risk, including for Aboriginal populations, and that socioeconomic determinants are associated with health risks. Our analyses showing that Aboriginal status itself contributes to injury risk is new, but we can only speculate about pathway, and whether the causes are direct or indirect.

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Identification of selective cytotoxic and synthetic lethal drug responses in triple negative breast cancer cells

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive type of cancer that lacks effective targeted therapy. Despite detailed molecular profiling, no targeted therapy has been established. Hence, with the aim of gaining deeper understanding of the functional differences of TNBC subtypes and how that may relate to potential novel therapeutic strategies, we studied comprehensive anticancer-agent responses among a panel of TNBC cell lines.MethodThe responses of 301 approved and investigational oncology compounds were measured in 16 TNBC cell lines applying a functional profiling approach. To go beyond the standard drug viability effect profiling, which has been used in most chemosensitivity studies, we utilized a multiplexed readout for both cell viability and cytotoxicity, allowing us to differentiate between cytostatic and cytotoxic responses. Results: Our approach revealed that most single-agent anti-cancer compounds that showed activity for the viability readout had no or little cytotoxic effects. Major compound classes that exhibited this type of response included anti-mitotics, mTOR, CDK, and metabolic inhibitors, as well as many agents selectively inhibiting oncogene-activated pathways. However, within the broad viability-acting classes of compounds, there were often subsets of cell lines that responded by cell death, suggesting that these cells are particularly vulnerable to the tested substance. In those cases we could identify differential levels of protein markers associated with cytotoxic responses. For example, PAI-1, MAPK phosphatase and Notch-3 levels associated with cytotoxic responses to mitotic and proteasome inhibitors, suggesting that these might serve as markers of response also in clinical settings. Furthermore, the cytotoxicity readout highlighted selective synergistic and synthetic lethal drug combinations that were missed by the cell viability readouts. For instance, the MEK inhibitor trametinib synergized with PARP inhibitors. Similarly, combination of two non-cytotoxic compounds, the rapamycin analog everolimus and an ATP-competitive mTOR inhibitor dactolisib, showed synthetic lethality in several mTOR-addicted cell lines. Conclusions: Taken together, by studying the combination of cytotoxic and cytostatic drug responses, we identified a deeper spectrum of cellular responses both to single agents and combinations that may be highly relevant for identifying precision medicine approaches in TNBC as well as in other types of cancers.

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Design, development and validation of a new laryngo-pharyngeal endoscopic esthesiometer and range-finder based on the assessment of air-pulse variability determinants

Background: Laryngo-pharyngeal mechano-sensitivity (LPMS) is involved in dysphagia, sleep apnea, stroke, irritable larynx syndrome and cough hypersensitivity syndrome among other disorders. These conditions are associated with a wide range of airway reflex abnormalities. However, the current device for exploring LPMS is limited because it assesses only the laryngeal adductor reflex during fiber-optic endoscopic evaluations of swallowing and requires a high degree of expertise to obtain reliable results, introducing intrinsic expert variability and subjectivity. Methods: We designed, developed and validated a new air-pulse laryngo-pharyngeal endoscopic esthesiometer with a built-in laser range-finder (LPEER) based on the evaluation and control of air-pulse variability determinants and on intrinsic observer variability and subjectivity determinants of the distance, angle and site of stimulus impact. The LPEER was designed to be capable of delivering precise and accurate stimuli with a wide range of intensities that can explore most laryngo-pharyngeal reflexes. Results: We initially explored the potential factors affecting the reliability of LPMS tests and included these factors in a multiple linear regression model. The following factors significantly affected the precision and accuracy of the test (P < 0.001): the tube conducting the air-pulses, the supply pressure of the system, the duration of the air-pulses, and the distance and angle between the end of the tube conducting the air-pulses and the site of impact. To control all of these factors, an LPEER consisting of an air-pulse generator and an endoscopic laser range-finder was designed and manufactured. We assessed the precision and accuracy of the LPEER's stimulus and range-finder according to the coefficient of variation (CV) and by looking at the differences between the measured properties and the desired values, and we performed a pilot validation on ten human subjects. The air-pulses and range-finder exhibited good precision and accuracy (CV < 0.06), with differences between the desired and measured properties at <3 % and a range-finder measurement error of <1 mm. The tests in patients demonstrated obtainable and reproducible thresholds for the laryngeal adductor, cough and gag reflexes. Conclusions: The new LPEER was capable of delivering precise and accurate stimuli for exploring laryngo-pharyngeal reflexes.

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Determining breast cancer histological grade from RNA-sequencing data

Background: The histologic grade (HG) of breast cancer is an established prognostic factor. The grade is usually reported on a scale ranging from 1 to 3, where grade 3 tumours are the most aggressive. However, grade 2 is associated with an intermediate risk of recurrence, and carries limited information for clinical decision-making. Patients classified as grade 2 are at risk of both under- and over-treatment. Methods: RNA-sequencing analysis was conducted in a cohort of 275 women diagnosed with invasive breast cancer. Multivariate prediction models were developed to classify tumours into high and low transcriptomic grade (TG) based on gene- and isoform-level expression data from RNA-sequencing. HG2 tumours were reclassified according to the prediction model and a recurrence-free survival analysis was performed by the multivariate Cox proportional hazards regression model to assess to what extent the TG model could be used to stratify patients. The prediction model was validated in N=487 breast cancer cases from the The Cancer Genome Atlas (TCGA) data set. Differentially expressed genes and isoforms associated with HGs were analysed using linear models. Results: The classification of grade 1 and grade 3 tumours based on RNA-sequencing data achieved high accuracy (area under the receiver operating characteristic curve = 0.97). The association between recurrence-free survival rate and HGs was confirmed in the study population (hazard ratio of grade 3 versus 1 was 2.62 with 95 % confidence interval = 1.04–6.61). The TG model enabled us to reclassify grade 2 tumours as high TG and low TG gene or isoform grade. The risk of recurrence in the high TG group of grade 2 tumours was higher than in low TG group (hazard ratio = 2.43, 95 % confidence interval = 1.13–5.20). We found 8200 genes and 13,809 isoforms that were differentially expressed between HG1 and HG3 breast cancer tumours. Conclusions: Gene- and isoform-level expression data from RNA-sequencing could be utilised to differentiate HG1 and HG3 tumours with high accuracy. We identified a large number of novel genes and isoforms associated with HG. Grade 2 tumours could be reclassified as high and low TG, which has the potential to reduce over- and under-treatment if implemented clinically.

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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

Thrombolytic therapy with intravenous alteplase (recombinant tissue-type plasminogen activator) at a dose of 0.9 mg per kilogram of body weight is an effective treatment for acute ischemic stroke, despite increasing the risk of intracerebral hemorrhage. However, the Japanese drug safety authority…

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Incorporation of an invasive plant into a native insect herbivore food web

The integration of invasive species into native food webs represent multifarious dynamics of ecological and evolutionary processes. We document incorporation of Prunus serotina (black cherry) into native insect food webs. We find that P. serotina harbours a herbivore community less dense but more diverse than its native relative, P. padus (bird cherry), with similar proportions of specialists and generalists. While herbivory on P. padus remained stable over the past century, that on P. serotina gradually doubled. We show that P. serotina may have evolved changes in investment in cyanogenic glycosides compared with its native range. In the leaf beetle Gonioctena quinquepunctata, recently shifted from native Sorbus aucuparia to P. serotina, we find divergent host preferences on Sorbus- versus Prunus-derived populations, and weak host-specific differentiation among 380 individuals genotyped for 119 SNP loci. We conclude that evolutionary processes may generate a specialized herbivore community on an invasive plant, allowing prognoses of reduced invasiveness over time. On the basis of the results presented here, we would like to caution that manual control might have the adverse effect of a slowing down of processes of adaptation, and a delay in the decline of the invasive character of P. serotina.

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Editorial.

Editorial.

J Cosmet Laser Ther. 2016 Jun;18(3):125

Authors: Goldberg DJ

PMID: 27158801 [PubMed - as supplied by publisher]

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Pharmaceutical cocrystals: walking the talk

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC02943D, Feature Article

Ashwini Nangia, Geetha Bolla
Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or active pharmaceutical ingredient, API) and the second is a benign food or...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Assessing patients’ attitudes to opt-out HIV rapid screening in community dental clinics: a cross-sectional Canadian experience

As a public health initiative, provided-initiated HIV screening test in dental settings has long been available in the U.S.; it was only in 2011 that such setting was used in Canada. The objective of this pape...

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Do hand preferences predict stacking skill during infancy?

Abstract

The cascade theory of handedness suggests that hand preferences develop from a history of cascading and sequentially developing manual asymmetries for a variety of actions. Infants who consistently use their preferred hand for a variety of actions likely would gain proficiency using that preferred hand and, consequently, perform more proficiently on other challenging manual tasks. One such task is object stacking, which has been linked with a number of cognitive abilities. If infant hand preference facilitates the development of stacking skill, then this could provide a link by which early hand preference might affect the development of cognition. From a sample of 380 infants assessed for an acquisition hand preference across 6–14 months, 131 infants were assessed for stacking skill from 10 to 14 months at monthly visits. Four unique handedness sub-groups were identified from the 380-infant sample: left, trending right, stable right, or no hand preference. Each of the four hand preference groups exhibited different trajectories in the development of their stacking skills. Left- and stable right-handers stacked more items than infants with no preference by 14 months, whereas infants with a trending right preference did not. The proportion of preferred hand use (right and left) from 6 to 9 months also predicted an earlier initial onset of stacking skill, whereas the proportion of only right hand use did not. Thus, the development of a hand preference predicts an earlier emergence of stacking skill and may have implications for other domains of infant cognitive development.

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Patterns of joint parasympathetic, sympathetic, and adrenocortical activity and their associations with temperament in early childhood

Abstract

Evidence has accrued to show that autonomic and adrenocortical systems act in coordination to facilitate responses to environmental opportunities and threats. In the current study, we used cluster analysis to examine whether individual differences in patterns of joint baseline activity among the parasympathetic and sympathetic branches of the autonomic nervous system with the hypothalamic-pituitary-adrenal axis are associated with parent-reported temperamental positive and negative affectivity in 36-month old children. The resulting clusters corresponded to the sensitive, buffered, and vigilant patterns as predicted by the adaptive calibration model of stress responsivity (Del Giudice et al., 2011) and included a novel pattern. Cluster memberships predicted differences in overall negative affectivity and its subscales, but no associations were found with positive affectivity. These results provide evidence that the joint activity of physiological systems at rest may underlie temperamental differences in negative affect.

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Effects of ethanol exposure in a familiar or isolated context during infancy on ethanol intake during adolescence

Abstract

Early exposure to ethanol affects ethanol intake later in life. This early experience encompasses exposure to social stimuli and the pharmacological and orosensory properties of ethanol. The specific contribution of each type of stimulus to subsequent ethanol intake remains unknown. We assessed the intake of various concentrations of ethanol in a familiar or isolated context during infancy and the lingering effects of this experience on ethanol intake during adolescence. On postnatal day 3 (PD3), PD7, and PD11, rats were given 5% ethanol or water in a nursing or isolated context (Experiments 1 and 2). Intake tests (ethanol vs. water) were conducted during adolescence. Experiment 2 matched the amount of fluid ingested during infancy in both contexts and subsequently tested ethanol consumption during adolescence. The results revealed a facilitative effect of the nursing context on fluid intake during the tests in infancy. Pups stimulated with ethanol but not water in the isolated context exhibited an increase in ethanol consumption during adolescence. This effect disappeared when the isolated infants were matched to receive the same amount of ethanol ingested by their nursed counterparts. In Experiment 3, isolated infant rats were exposed to different ethanol concentrations (.0%, 2.5%, 5.0%, and 10.0%), and drug consumption was tested during adolescence. This exposure increased adolescent ethanol intake, regardless of the alcohol concentration (Experiment 3). The common denominators that resulted in enhanced ethanol intake during adolescence were preexposure to ethanol via active consumption of the drug that induced a low-to-moderate level of intoxication in an isolated context.

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Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack

Ischemic stroke and transient ischemic attack are common, and the risk of subsequent ischemic events is particularly high during the first 90 days after the index cerebrovascular event. Aspirin at a dose of 50 to 325 mg daily is commonly used in this context. However, the benefit of aspirin in the…

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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

Thrombolytic therapy with intravenous alteplase (recombinant tissue-type plasminogen activator) at a dose of 0.9 mg per kilogram of body weight is an effective treatment for acute ischemic stroke, despite increasing the risk of intracerebral hemorrhage. However, the Japanese drug safety authority…

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Finding the Right t-PA Dose for Asians with Acute Ischemic Stroke

The efficacy of intravenous thrombolysis with tissue plasminogen activator (t-PA) for improving outcomes in patients with acute ischemic stroke has driven the infrastructure development for acute stroke care delivery in the United States, Europe, and Australia for the past 20 years. The early…

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Sampling Rate, Signal Bandwidth and Related Pitfalls in EEG Analysis

Publication date: Available online 9 May 2016
Source:Journal of Neuroscience Methods
Author(s): Marco Weiergräber, Anna Papazoglou, Karl Broich, Ralf Müller
This submission contains a commentary.



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Prolongation of ERP latency and reaction time (RT) in simultaneous EEG/fMRI data acquisition

Publication date: Available online 9 May 2016
Source:Journal of Neuroscience Methods
Author(s): Jinsoo Chun, Scott J. Peltier, Daehyun Yoon, Theo C. Manschreck, Patricia J. Deldin
BackgroundRecording EEG and fMRI data simultaneously inside a fully-operating scanner has been recognized as a novel approach in human brain research. Studies have demonstrated high concordance between the EEG signals and hemodynamic response. However, a few studies reported altered cognitive process inside the fMRI scanner such as delayed reaction time (RT) and reduced and/or delayed N100 and P300 event-related brain potential (ERP) components.New MethodThe present study investigated the influence of electromagnetic field (static magnetic field, radio frequency (RF) pulse, and gradient switching) and experimental environment on posterior N100 and P300 ERP components in four different settings with six healthy subjects using a visual oddball task: (1) classic fMRI acquisition inside the scanner (e.g., supine position, mirror glasses for stimulus presentation), (2) standard behavioral experiment outside the scanner (e.g., seated position, keyboard response), (3) controlled fMRI acquisition inside the scanner (e.g., Organic Light-Emitting Diode (OLED) goggles for stimulus presentation) inside; and (4) modified behavioral experiment outside the scanner (e.g., supine position, OLED goggles).ResultsThe study findings indicated that the experimental environment in simultaneous EEG/fMRI acquisition could substantially delay N1P, P300 latency, and RT inside the scanner, and was associated with a reduced N1P amplitude.Comparison with existing methodsThere was no effect of electromagnetic field in the prolongation of RT, N1P and P300 latency inside the scanner. N1P, but not P300, latency was sensitive to stimulus presentation method inside the scanner.ConclusionFuture simultaneous EEG/fMRI data collection should consider experimental environment in both design and analysis.



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How integrated are neurology and palliative care services? Results of a multicentre mapping exercise

Patients affected by progressive long-term neurological conditions might benefit from specialist palliative care involvement. However, little is known on how neurology and specialist palliative care services i...

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AIMS Baby movement scale application in high-risk infants early intervention analysis

OBJECTIVE: We investigated the application of Alberta Infant Motor Scale (AIMS) in screening motor development delay in the follow-up of high-risk infants who were discharged from NICU, to explain the state of infants' motor development and propose early individualized intervention.

PATIENTS AND METHODS: The study design was a randomized, single-blind trial by selecting patients between April 2015 and November 2015 in our hospital, children nerve recovery branch clinics and 77 cases of high-risk infants. We randomly divided the patients into observation group (39 cases) and control group (38 cases). To evaluate the application with AIMS, observation group was based on evaluation results for the first time to give rehabilitation training plan making, early intervention, control group according to the growth and development milestone in order to guide parents to take family training interval of 3 months.

RESULTS: While comparing the two groups of high-risk infants before the intervention, the months of age, gender, risk factors, it was found that the AIMS scores, each position AIMS scores did not show a significant difference in percentile (p>0.05). There was also no significant difference between two groups in the seat and stand AIMS scores before and after intervention (p>0.05). However, the comparison of two groups of high-risk infants after intervention in comparison showed that the observation group supine AIMS scores and AIMS scores were significantly higher than the control group (p<0.05). Prone position AIMS scores observation group was also significantly higher than that of the control group (p<0.01). The corresponding percentile for two groups after the intervention of AIMS scores was less than 10% of cases, which was significantly lower in the observation group (p<0.01).

CONCLUSIONS: AIMS can predict the development delay in high-risk infants, for improving the early hypernymic diagnosis and intervention.

L'articolo AIMS Baby movement scale application in high-risk infants early intervention analysis sembra essere il primo su European Review.

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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

Thrombolytic therapy with intravenous alteplase (recombinant tissue-type plasminogen activator) at a dose of 0.9 mg per kilogram of body weight is an effective treatment for acute ischemic stroke, despite increasing the risk of intracerebral hemorrhage. However, the Japanese drug safety authority…

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Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack

Ischemic stroke and transient ischemic attack are common, and the risk of subsequent ischemic events is particularly high during the first 90 days after the index cerebrovascular event. Aspirin at a dose of 50 to 325 mg daily is commonly used in this context. However, the benefit of aspirin in the…

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Finding the Right t-PA Dose for Asians with Acute Ischemic Stroke

The efficacy of intravenous thrombolysis with tissue plasminogen activator (t-PA) for improving outcomes in patients with acute ischemic stroke has driven the infrastructure development for acute stroke care delivery in the United States, Europe, and Australia for the past 20 years. The early…

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Diet and predatory behavior of the Asian ant-eating spider, Asceua (formerly Doosia) japonica (Araneae: Zodariidae)

Several spider taxa are specialized to prey on ants. Some species of Zodariidae are known to use specialized tactics to capture ants. In this study, I assessed the diet difference and predatory behavior of the...

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Prevalence of Chlamydia trachomatis infection in parturient women in Gipuzkoa, Northern Spain

The prevalence of Chlamydia trachomatis infection in Southern Europe is poorly understood and its identification is essential for the design of appropriate prevention policies. The prevalence of C. trachomatis in...

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Comparison of the effects of patient controlled analgesia (PCA) using dexmedetomidine and propofol during septoplasty operations: a randomized clinical trial

Septoplastical surgery to correct septum deviation can be performed under either local or general anesthesia. During local anesthesia, sedation helps to provide minimum anxiety/discomfort. Our aim was to eval...

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