Study of NC-6004 in Combination With 5-FU and Cetuximab in Patients With Head and Neck Cancer

Condition:   Head and Neck Neoplasms
Interventions:   Drug: NC-6004;   Drug: Cetuximab;   Drug: 5-FU
Sponsors:   Orient Europharma Co., Ltd.;   Nanocarrier Co., Ltd.
Recruiting - verified June 2016

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Effect of laser-activated irrigation on biofilms in artificial root canals

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YAGG:Cr3+ as NIR persistent phosphor for in vivo imaging

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The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography-tandem mass spectrometry

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Iododerma from Contrast Material: NEJM Case Report

• NEJM reports a image case of iododerma, patient after  Intravenous urography, Several hours later, generalized pustular eruptions developed, with multiple coalescing vesicles and pus-filled bullae observed on the patient's face and ears, his trunk, and his arms and legs. 

• Although its pathogenesis is not understood, delayed iodine clearance and the induction of neutrophil degranulation have been proposed as mechanisms. 

• Treatment with thalidomide was initiated, and the skin lesions completely resolved within 4 weeks.

Reference: Iododerma from Contrast Material. Juan Guillermo Chalela, M.D., and Laura Aguilar, M.D. N Engl J Med 2016; 374:2477June 23, 2016DOI: 10.1056/NEJMicm1512512

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3D Helical and 2D Rhomboidal Supramolecules: Stepwise Self-Assembly and Dynamic Transformation of Terpyridine-Based Metallo-Architectures

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04482D, Communication

Die Liu, Zhilong Jiang, Ming Wang, Xiaoyu Yang, Haisheng Liu, Mingzhao Chen, Charles N. Moorefield, George R Newkome, Xiaopeng Li, Pingshan Wang
A Ru2+-connected, metallo-organic ligand (L) with three free terpyridines was designed and synthesized. L was assembled with Zn2+ to generate a helical structure; however, when mixing L with 1,2,3-tristerpyridine ligand...
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Gold-Catalyzed Intermolecular Formal (3+2) Cycloaddition of Stabilized Vinyldiazo Derivatives and Electronically Unbiased Allenes

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04106J, Communication

Enol Lopez, Giacomo Lonzi, Francisco Javier Gonzalez , Luis A. Lopez
The reaction of electronically unbiased allenes with alkenyldiazo compounds in the presence of gold catalysts provided alkylidenecyclopentene derivatives resulting from a formal intermolecular (3+2) carbocyclization. A stepwise mechanism involving initial...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Cavity-Containing Supramolecular Gels as a Crystallization Tool for Hydrophobic Pharmaceuticals

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04037C, Communication

Lena Kaufmann, Stuart R. Kennedy, Christopher David Jones, Jonathan W Steed
We present two approaches to low-molecular-weight supramolecular gels bearing hydrophobic cavities based on calixarene-containing building blocks. Gels are formed by a calixarene based tetrahydrazide gelator or a co-gel of a...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.

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10 obsolete EMT skills

Nothing makes me feel older than when I drop a casual reference to an EMT skill in a continuing education class and several bewildered young EMTs raise their hands hesitantly and ask, "Kelly, what are MAST pants""

It got me to thinking how different the EMS profession is now from what it was when my career began. Medicine is a continually evolving process, and advances in technology come so rapidly that the current generation of EMS providers is working with a markedly different knowledge base and set of skills than the last one.

So gather around the campfire children and let Uncle Kelly tell you how we did it in the old days. Each of these 10 skills is something we used to commonly do, but are rarely, if ever, used any longer.

10. Pneumatic Anti-Shock Garments
I only spell it out because if I said MAST or PASG, I'd still have to explain it to you young whippersnappers. See, back in the day we used to put these inflatable Velcro pants on shock patients, and when inflated, it raised their blood pressure. It did raise blood pressure very well — to the point that the patient bled pink from all the IV fluids we gave, but those magic pants sucked at saving lives.

Not only did we have to know the different methods of applying them, like the diaper method and the pajama method, we also had to memorize the criteria for removal. Dinosaurs, say them with me now: "Bilateral large bore IV access, two units of typed and matched blood, surgical team on standby, deflate the abdominal section for 10 seconds, recheck the blood pressure …"

9. Manual defibrillation paddles
You kids these days with your hippity-hop music and your iThings and your hands-free multifunction electrodes.… Why, in my day, when we wanted to defibrillate someone, we had these things called paddles. And you had to apply conductive gel to them and smear it around; then you had to press them on the chest with at least 25 pounds of paddle pressure

And you had your energy select dial and defib button right there on the paddles. And you did this thing called a quick look, so that you could immediately shock the patient, like, three times in a row, before you even attached the monitor leads.

And by God, we were grateful.

8. Esophageal Obturator Airways
Imagine if a Combitube and a BVM had a baby, and the airway baby inherited the worst features of each. The EOA was a supraglottic airway that was bulky, often caused trauma on insertion, did a poor job of isolating the trachea and protecting against aspiration and still required that you maintain a mask seal.

And to think that nobody uses these beauties anymore! Crazy, right"

7. Oral screws
Picture — because I am afraid of what you might stumble across if you Google "oral screws" — if you will a little plastic doohickey shaped like a miniature ice cream cone with threads on the outer surface and a T-handle on the large end. And what you did was insert the small end of this doohickey between someone's teeth when their jaws were clenched, and screwed it in until it forced their jaws apart.

We used to do this whenever someone had a seizure, in the mistaken belief that if we didn't get their mouth open, they'd swallow their tongue.

But the real reason was that it gave paramedics with a juvenile sense of humor the opportunity to hold out their hands and bark, "Gimme an oral screw!"

I'm telling you, that one never got old.

6. Taping stuff down
When I was a paramedic student, my instructor took great pains to show us how to tear thin little strips of adhesive tape to secure IV catheters and endotracheal tubes. We fashioned elegant little chevrons of tape over the wings on our IV catheter hubs (seriously, they had wings) to secure them without obscuring the cannulation site. And we used to tear a one-inch strip of tape longitudinally for a few inches, wrapping one strip around the endotracheal tube and the other across the face like a big mustache.

And then someone would promptly rip our IV or endotracheal tube out while we were loading the patient, so we got to do it again.

Nowadays we have tube holders and IV dressings, and taping is a lost art like calligraphy and darning your socks.

5. Rotating tourniquets
Once upon a time, we used to think that acute pulmonary edema and decompensated congestive heart failure was caused by too much blood re-entering the lungs. We thought that if we could trap blood in the extremities, we'd reduce preload enough to relieve the pulmonary edema.

So we applied humongous blood pressure cuffs on three of the patient's four extremities, inflated them to just above diastolic pressure, and rotated them around the patient's extremities every 15 minutes.

And it took us only a generation or so to discover that it was stupid and didn't work.

4. Trendelenburg position
For many years we fervently believed the Trendelenburg position was a vital treatment for shock. We thought that elevating the feet higher than the head raised blood pressure, and maybe even caused a couple units of blood to flow from the legs to the trunk.

Turns out it doesn't really do those things, and instead caused respiratory decompensation and a rise in intracranial pressure. Still, that doesn't keep some EMTs working for the EMS Agency That Time Forgot from carefully applying and documenting "patient placed in Trendelenburg position."

3. Standing takedowns
Now that our current understanding of spinal cord injury acknowledges that prehospital spinal immobilization on backboards has virtually no supporting evidence and probably does more harm than good, we're boarding far fewer people these days.

While the adage holds true that "absence of evidence does not mean evidence of absence," and there may be some yet-undiscovered tiny subset of patients that benefit from strapping a curved body to a flat board, it's a pretty safe bet that subset does not include people walking around the scene under their own power.

2. External jugular IV access
Honestly, I really miss this one. The EJ used to be my go-to vein in a code. I was already right there at the head intubating, and all it took was turning the patient's head to one side a bit, sinking a 14-gauge in that fat, engorged vein, and you had the mother of all peripheral IV accesses.

You know, we did this so all those questionably beneficial drugs we gave could reach the heart that much faster. Now, with mechanical IO devices like the EZ-IO in my repertoire, I can't remember the last time I started an EJ.

Adult IO devices have really revolutionized emergency peripheral vascular access. And not a moment too soon, either, before this intracavernous technique really caught on.

1. Radio 10 codes
Once upon a time, we used to take sadistic pleasure in rapid fire broadcasting to the brand-new dispatcher, "Dispatch, we're 10-98, 10-8, 10-19, 10-18 to our 10-42, where we'll be 10-7 for a few minutes for a 10-33 10-100. If we're not 10-2 on that, we'll be happy to 10-9."

Now that we communicate in plain English because 10 codes are confusing and vary between agencies, we get to say, "Dispatch, we've completed our last assignment and are available for call, but we're heading to our station as soon as possible because my partner will be out of service taking an emergency all-he-could-eat taco buffet poop. If you didn't copy all that, I'm willing to repeat it."

Or at least we get to say that once.

I could think of a few more EMT skills that may soon become obsolete if we don't get better at applying them, but that's my list of top 10 obsolete EMT skills.

Got any to add to the list" Chime in with yours in the comments.

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Highly solvatochromic and tunable fluorophores based on a 4,5-quinolimide scaffold: Novel CDK5 probes

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04566A, Communication

Juan A. Gonzalez-Vera, Francisco Fueyo-Gonzalez, Ibon Alkorta, Marion Peyressatre, May C. Morris, ROSARIO HERRANZ
Novel 4,5-quinolimide-based fluorophores are more solvatochromic and red-shifted than known naphthalimide analogues. Conjugation of one of these fluorophores to a peptide derived from CDK5 kinase demonstrated its sensitivity for monitoring...
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High oxygen tension increases global methylation in bovine 4-cell embryos and blastocysts but does not affect general retrotransposon expression

Retrotransposons are transposable elements that insert extra copies of themselves throughout the genome via an RNA intermediate using a copy and paste' mechanism. They account for more than 44% of the bovine genome and have been reported to be functional, especially during preimplantation embryo development. In the present study, we tested whether high oxygen tension (20% O-2) influences global DNA methylation analysed by immunofluorescence staining of developing bovine embryos and whether this has an effect on the expression of some selected retrotransposon families. High oxygen tension significantly increased global DNA methylation in 4-cell embryos and blastocysts. A significant expression difference was observed for ERV1-1-I_BT in female blastocysts, but no significant changes were observed for the other retrotransposon families tested. Therefore, the study indicates that global DNA methylation is not necessarily correlated with retrotransposon expression in bovine preimplantation embryos.

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LiGa5O8:Cr3+ as NIR persistent phosphor for in vivo imaging

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Seroprevalence and risk factors associated with brucellosis as a professional hazard in Pakistan

The present study was conducted to determine the seroprevalence and identify risk factors associated with brucellosis in humans at high risk in the Potohar plateau of northeastern Pakistan. A total of 262 serum samples were collected from persons of different occupational groups: veterinary personnel, milkers, abattoir workers, livestock farmers, and others (drivers, security guards, housewives). Data related to gender, age, occupation, contact with animals, brucellosis-related symptoms, consumption of raw milk, and geographical region were collected. The Rose Bengal plate test and the serum agglutination test were performed to determine the seroprevalence of brucellosis. The overall seroprevalence was found to be 6.9% (95% confidence interval [CI]: 4.1, 10.6). Real-time polymerase chain reaction assay showed that all cases were affected by Brucella abortus. Individuals who consumed raw milk had higher odds of brucellosis seropositivity. This is the first report of human brucellosis related to B. abortus in high-risk professionals from Pakistan by the combined use of serological and molecular methods.

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Seroprevalence and risk factors for brucellosis in a high-risk group of individuals in Bangladesh

Brucellosis is an occupational hazard of livestock farmers, dairy workers, veterinarians, slaughterhouse workers, and laboratory personnel, all of whom are considered to belong to the high-risk occupational group (HROG). A study was undertaken to determine the seroprevalence of brucellosis, identify risk factors associated with brucellosis seropositivity, and detect Brucella at genus level using real-time polymerase chain reaction (PCR) among people in the HROG in the Dhaka division of Bangladesh. A sample of 500 individuals from the HROG was collected from three districts of Dhaka division of Bangladesh. A multiple random effects logistic regression model was used to identify potential risk factors. Two types of real-time PCR methods were applied to detect Brucella genus-specific DNA using serum from seropositive patients. The prevalence of brucellosis based on the three tests was observed to be 4.4% based on a parallel interpretation. The results of the multiple random effects logistic regression analysis with random intercept for district revealed that the odds of brucellosis seropositivity among individuals who had been in contact with livestock for more than 26 years was about 14 times higher as compared to those who had less than 5 years of contact with livestock. In addition, when the contact was with goats, the odds of brucellosis seropositivity were about 60 times higher as compared to when contact was with cattle only. Noticeable variation in brucellosis seropositivity among humans within the three districts was noted. All of the 13 individuals who tested positive for the serological tests were also positive in two types of real-time PCR using the same serum samples. Livestock farmers of brucellosis positive herds had a significantly higher probability to be seropositive for brucellosis. The study emphasized that contact with livestock, especially goats, is a significant risk factor for the transmission of brucellosis among individuals in the HROG.

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Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecal Escherichia coli

Fifty-two newborn Holstein calves with serum IgG concentrations less than 0.73 g.dL(-1) were randomly assigned to one of four treatments: no added live yeast (control), 0.5 g of live yeast added to the grain for 84 d (SC; Saccharomyces cerevisiae), 0.5 g of live yeast added to the milk for 42 d (SB; S. cerevisiae, spp. boulardii), and 0.5 g of live yeast added to the grain for 84 d and to the milk for 42 d (SCSB). Calves were offered 440 g of milk replacer DM for the first 42 d and grain for ad libitum intake throughout the study. Plasma was analyzed weekly for concentrations of glucose and beta-hydroxybutyrate. Escherichia coli isolated from fecal samples collected every 2 weeks were used for determination of antibiotic resistance patterns. Calves receiving SC consumed more grain DM, had increased weight gain prior to weaning, and increased plasma glucose concentrations compared to controls. Days with diarrhea were reduced by feeding live yeast to calves. Antibiotic resistance in fecal E. coli was associated with the age of calves with highest levels of resistance observed in the 3 d calves. While calves receiving SCSB had higher levels of antibiotic resistance than controls, this effect was not associated with any of the other treatments. Improvements in performance of calves with failure of passive transfer were observed when live yeast was added only to the grain.

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Polish circular migration and marginality: a livelihood strategy approach

White, A; (2016) Polish circular migration and marginality: a livelihood strategy approach. Studia Migracyjne – Przegląd Polonijny , 1 (159) pp. 153-166. Gold open access

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ICME international survey on teachers working and learning through collaboration

Robutti, O; Cusi, A; Clark-Wilson, A; Chapman, O; Esteley, C; Goos, M; Isoda, M; Robutti, O; Cusi, A; Clark-Wilson, A; Chapman, O; Esteley, C; Goos, M; Isoda, M; Jaworski, B; Joubert, M; - view fewer (2016) ICME international survey on teachers working and learning through collaboration. ZDM (In press).

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Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach

McCrory, EJ; Mayes, L; (2015) Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach. Current Addiction Reports , 2 (4) pp. 326-330. 10.1007/s40429-015-0079-2 . Green open access

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Exchange calculations between donors in silicon and metal-phthalocyanine dimer.

Wu, W.; (2007) Exchange calculations between donors in silicon and metal-phthalocyanine dimer. Doctoral thesis, University of London. Green open access

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Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years

Aguiar, R; Araújo, C; Martins-Coelho, G; Isenberg, D; (2016) Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years. Arthritis Care & Research 10.1002/acr.22921 . (In press).

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Elucidating molecular mechanisms of leukaemogenesis in normal karyotype AML.

Smith, S.L-L.; (2008) Elucidating molecular mechanisms of leukaemogenesis in normal karyotype AML. Doctoral thesis, University of London. Green open access

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Optimal Exercise Strategies for Operational Risk Insurance via Multiple Stopping Times

Targino, RS; Peters, GW; Sofronov, G; Shevchenko, PV; (2016) Optimal Exercise Strategies for Operational Risk Insurance via Multiple Stopping Times. Methodology and Computing in Applied Probability 10.1007/s11009-016-9493-8 . (In press). Green open access

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A study of the influence of ethnicity on serology and clinical features in lupus

Morais, SA; Isenberg, DA; (2016) A study of the influence of ethnicity on serology and clinical features in lupus. Lupus 10.1177/0961203316645204 . (In press).

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Autoimmune gastrointestinal complications in patients with Systemic Lupus Erythematosus: case series and literature review

Custódio Alves, S; Fasano, S; Isenberg, DA; (2016) Autoimmune gastrointestinal complications in patients with Systemic Lupus Erythematosus: case series and literature review. Lupus 10.1177/0961203316655210 . (In press). Green open access

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Analysis of complete remission in systemic lupus erythematosus patients over a 32-year period

Medina-Quiñones, CV; Ramos-Merino, L; Ruiz-Sada, P; Isenberg, DA; (2016) Analysis of complete remission in systemic lupus erythematosus patients over a 32-year period. Arthritis Care and Research , 68 (7) pp. 981-987. 10.1002/acr.22774 .

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Experiences and perspectives of children attending a weight loss camp in China: a qualitative study

Li, X; Zhou, X; Hesketh, T; (2016) Experiences and perspectives of children attending a weight loss camp in China: a qualitative study. Child: Care, Health and Development 10.1111/cch.12353 . (In press).

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Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo

Hebden, JC; Chitnis, D; Airantzis, D; Highton, D; Williams, R; Phan, P; Giagka, V; Hebden, JC; Chitnis, D; Airantzis, D; Highton, D; Williams, R; Phan, P; Giagka, V; Powell, S; Cooper, RJ; Tachtsidis, I; Smith, M; Elwell, C; Everdell, N; - view fewer (2016) Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo. Review of Scientific Instruments , 87 (6) , Article 065112. 10.1063/1.4954722 .

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Induced pluripotent stem cell models of frontotemporal dementia

Preza, E; Hardy, J; Warner, T; Wray, S; (2016) Induced pluripotent stem cell models of frontotemporal dementia. Neuropathology and Applied Neurobiology 10.1111/nan.12334 . (In press).

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Observing mealworms in the primary classroom

Tunnicliffe, SD; (2016) Observing mealworms in the primary classroom. Journal of Emergent Science (In press).

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Children's science learning: a core skills approach

Tolmie, AK; Ghazali, Z; Morris, S; (2016) Children's science learning: a core skills approach. British Journal of Educational Psychology 10.1111/bjep.12119 . (In press).

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Authors' Reply

Respiration

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Evaluation of Transbronchial Lung Cryobiopsy Size and Freezing Time: A Prognostic Animal Study

Background: Transbronchial lung biopsy using a cryoprobe is a novel way of sampling lung parenchyma. Correlation of freezing time with biopsy size and complications has not been evaluated in vivo. Objectives: The primary aim of the study is to evaluate the correlation between transbronchial cryobiopsy freezing time and size. The secondary aims are to evaluate histological quality of the biopsy and evaluate procedure-associated complications. Methods: Transbronchial lung cryobiopsies were obtained from two anaesthetised sheep using a 1.9-mm cryoprobe inserted into a flexible bronchoscope under fluoroscopic guidance. Freezing times ranged from 1 to 6 s (n = 49). The cryobiopsies were evaluated histologically with respect to their size and quality. Complications of bleeding and pneumothorax were recorded. Results: The mean cross-sectional area of the cryobiopsy ranged from 4.7 ± 2.1 to 15.7 ± 15.3 mm². There was a significant positive correlation between increasing freezing time and cryobiopsy cross-sectional area (p = 0.028). All biopsies contained lung tissue with preserved parenchyma. Crush and freeze artefacts were not observed and tissue architecture was intact in all specimens. Small blood vessels and terminal bronchioles were observed in 88% of specimens. All cryobiopsies caused nil or mild haemorrhage with the exception of only 1 episode of severe haemorrhage at 6 s freezing time. Pneumothoraces occurred at 2, 5 and 6 s freezing time and required chest tube insertion. The most significant haemorrhage and pneumothoraces occurred at 5 and 6 s. Our results suggest an initial freezing time of 3 s can provide the maximal biopsy size while minimising major complications. Conclusion: The optimal transbronchial cryobiopsy freezing time is initially 3 s. This time is associated with minimal complications and large artefact-free biopsies.
Respiration

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The Feasibility of Tracheal Oxygen Supplementation during Flexible Bronchoscopy

Background: Hypoxemia is a frequent adverse event occurring during flexible bronchoscopy and is usually prevented by close monitoring and, if needed, oxygen supplementation by nasal cannula. Objective: We aim to demonstrate that tracheal oxygen supplementation during flexible bronchoscopy is a feasible, safe and effective method to restore oxygen saturation levels after oxygen desaturation. Methods: In a first phase, we compare oxygen supplementation by the tracheal or nasal route in a single blinded cross-over design in healthy volunteers. In a second phase, we study patients referred for diagnostic flexible bronchoscopy, who desaturate despite oxygen supplementation by nasal cannula, in order to assess the ability to correct hypoxemia through tracheal oxygen supplementation. Results: In the first phase, the mean capillary partial pressure of oxygen was 181 mm Hg when oxygen at a flow rate of 4 liters/min was administered by the tracheal route, compared to 125 mm Hg by the nasal route (p Conclusions: Tracheal oxygen supplementation is safe, feasible and an effective way to restore oxygen saturation levels during flexible bronchoscopy.
Respiration

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Antimuscarinic Bronchodilator Response Retained after Bronchoscopic Vagal Denervation in Chronic Obstructive Pulmonary Disease Patients

Respiration

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The relation between input-output transformation and gastrointestinal nematode infections on dairy farms

Efficiency analysis is used for assessing links between technical efficiency (TE) of livestock farms and animal diseases. However, previous studies often do not make the link with the allocation of inputs and mainly present average effects that ignore the often huge differences among farms. In this paper, we studied the relationship between exposure to gastrointestinal (GI) nematode infections, the TE and the input allocation on dairy farms. Although the traditional cost allocative efficiency (CAE) indicator adequately measures how a given input allocation differs from the cost-minimising input allocation, they do not represent the unique input allocation of farms. Similar CAE scores may be obtained for farms with different input allocations. Therefore, we propose an adjusted allocative efficiency index (AAEI) to measure the unique input allocation of farms. Combining this AAEI with the TE score allows determining the unique input-output position of each farm. The method is illustrated by estimating efficiency scores using data envelopment analysis (DEA) on a sample of 152 dairy farms in Flanders for which both accountancy and parasitic monitoring data were available. Three groups of farms with a different input-output position can be distinguished based on cluster analysis: (1) technically inefficient farms, with a relatively low use of concentrates per 1001 milk and a high exposure to infection, (2) farms with an intermediate TE, relatively high use of concentrates per 1001 milk and a low exposure to infection, (3) farms with the highest TE, relatively low roughage use per 1001 milk and a relatively high exposure to infection. Correlation analysis indicates for each group how the level of exposure to GI nematodes is associated or not with improved economic performance. The results suggest that improving both the economic performance and exposure to infection seems only of interest for highly TE farms. The findings indicate that current farm recommendations regarding GI nematode infections could be improved by also accounting for the allocation of inputs on the farm.

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Ahead of print: Leistung und Gesundheit von Milchkühen: Bedeutung von Genetik (Ursache) und...

Die Milchleistung der Kühe hat sich in den letzten Jahrzehnten aufgrund der Selektion auf Milchmenge, entsprechender Fütterung, veterinärmedizinischer Betreuung und erfolgreichen Managements kontinuierlich erhöht und es ist anzunehmen, dass sich dieser Trend fortsetzen wird. Mit der Milchleistung haben jedoch die Erkrankungsrate zu- und die Nutzungsdauer abgenommen. Umfangreiche Untersuchungen der Tierzucht zeigten genetische Korrelationen zwischen Milchleistung und Erkrankungen wie Ketose/Leberverfettung, Mastitis, Klauenerkrankungen, Metritis (alle entzündlichen Formen) und Abnahme der Fruchtbarkeit auf, deren Pathogenese im Wesentlichen durch die negative Energiebilanz als Folge der Selektion auf hohe Milchleistung kausal bestimmt wird. Die genetische Disposition wird in der Praxis durch Managementfaktoren beeinflusst und diese Wechselwirkungen bestimmen die Inzidenz der Erkrankungen und deren hohe Variation. Es muss also bei der Analyse der Erkrankungen unterschieden werden zwischen der genetischen Disposition (Ursache) und Managementfaktoren (Wirkungen). Eine nachhaltige Verbesserung der Situation schließt die Überprüfung der Zuchtwerte und damit der Selektionskriterien ein....

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Validity and Reliability Concerns Associated with Cardiopulmonary Exercise Testing Young People with Cystic Fibrosis

Respiration

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Ahead of print: Mastitis vaccination using a commercial polyvalent vaccine or a herd-specific...

Objective of this study was the improvement of selected parameters of udder health by mastitis vaccination in a dairy herd with elevated bulk milk somatic cell counts and Staphylococcus (S.) aureus as predominant mastitis causing pathogen. Material and methods: On a dairy farm, pregnant heifers (status group [SG] 1; n = 181) as well as cows stratified for their udder health state (classification based on results of cytobacteriological investigations of quarter milk samples obtained before dry cow therapy [MS0]) (SG 2–4; n = 416) were randomly assigned to one of the following vaccination groups (VG): Startvac® (VG SV), Bestvac® Rind Mastitis (containing herd-specific S. aureus-strains; VG BV) and the unvaccinated control (VG Co, placebo), respectively. The collected data (5 [MS5] and 52 [MS52] days in milk [DIM]: quarter milk somatic cell count [QSCC] and bacteriological investigation of quarter milk samples; dairy herd improvement test [DHIT] days 1–10: milk yield and individual cow somatic cell count; until 305 DIM: clinical mastitis cases) were compared between the VG within their SG. Results: S. aureus prevalences were significantly lower in VG SV (p < 0.001) and VG BV (p = 0.006) within SG 3 and in VG SV (p = 0.008) within SG 4, respectively, in comparison to VG Co. Milk yields (DHIT days [p = 0.042] and 305-day milk yield [p = 0.040]) were significantly less in VG SV within SG 4 compared to VG Co. Significant different changes over time in comparison to VG Co indicating a vaccine effect during lactation were only observed for QSCC within SG 4 for VG BV (p = 0.017; increase towards MS52) and for S. aureus prevalence within SG 3 for VG BV (p < 0.001; opposing trends from MS0 towards MS52). All other interactions of time and VG under investigation were not significant in any of the SG. Furthermore, there were no descriptive differences in the incidence of clinical mastitis and duration of a necessary mastitis therapy, respectively, between the VG within their SG. Conclusion: In this field study, the application of two different mastitis vaccines was not an appropriate tool to improve the considered parameters of udder health sustainably....

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Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects

No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA) measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC), total trefoil (TF), total spherical aberration (TSA), and total higher order aberration (HOA) were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France). The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (). A significant increase was observed in TF and HOA measurements following coffee intake ( and , resp.). Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects.

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Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier

Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (

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MALAT1 induces tongue cancer cells' EMT and inhibits apoptosis through Wnt/β-catenin signaling pathway

Background

MALAT1 is recognized as an oncogenic lncRNA in various malignancies. However, its expression and function in oral tongue squamous cell carcinoma are still unknown. This study aims to investigate the expression and function of MALAT1 in TSCC tissues and cells.

Materials and Methods

qPCR was performed to detect the expression of MALAT1. MALAT1 was suppressed and upregulated by plasmid transfection in TSCC cells, and then cell migration, invasion, EMT, and apoptosis were analyzed.

Results

LncRNA MALAT1 was upregulated in TSCC tissues and correlated with cervical lymph node metastasis in TSCC patients. Moreover, MALAT1 induced cell migration, invasion, EMT, and inhibited apoptosis by modulating Wnt/β-catenin signaling pathway. Finally, inhibiting Wnt/β-catenin signaling pathway attenuated the effect of exogenous MALAT1.

Conclusion

In summary, upregulated MALAT1 in TSCC promoted EMT and inhibited cell apoptosis by modulating Wnt/β-catenin signaling pathway.

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Simplifying the Welfare Quality® assessment protocol for broiler chicken welfare

Welfare Quality((R)) (WQ) assessment protocols place the emphasis on animal-based measures as an indicator for animal welfare. Stakeholders, however, emphasize that a reduction in the time taken to complete the protocol is essential to improve practical applicability. We studied the potential for reduction in time to complete the WQ broiler assessment protocol and present some modifications to the protocol correcting a few errors in the original calculations. Data was used from 180 flocks assessed on-farm and 150 flocks assessed at the slaughter plant. Correlations between variables were calculated, and where correlation was moderate, meaningful and promising (in terms of time reduction), simplification was considered using one variable predicted from another variable. Correlation analysis revealed a promising correlation between severe hock burn and gait scores on-farm. Therefore, prediction of gait scores using hock burn scores was studied further as a possible simplification strategy (strategy 1). Measurements of footpad dermatitis, hock burn, cleanliness and gait score on-farm correlated moderately to highly with slaughter plant measurements of footpad dermatitis and/or hock burn, supporting substitution of on-farm measurements with slaughter plant data. A simplification analysis was performed using footpad dermatitis, hock burn, cleanliness and gait scores measured on-farm predicted from slaughter plant measurements of footpad dermatitis and hock burn (strategy 2). Simplification strategies were compared with the full assessment protocol. Close agreement was found between the full protocol and both simplification strategies although large confidence intervals were found for specificity of the simplified models. It is concluded that the proposed simplification strategies are encouraging; strategy 1 can reduce the time to complete the on-farm assessment by similar to 1 h (25% to 33% reduction) and strategy 2 can reduce on-farm assessment time by similar to 2 h (50% to 67% reduction). Both simplification strategies should, however, be validated further, and tested on farms with a wide distribution across the different welfare categories of WQ.

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Effect of rubber flooring on group-housed sows' gait and claw and skin lesions

This study evaluated the influence of floor type on sow welfare in terms of lameness, claw lesions, and skin lesions. In a 2 x 3 factorial design, we have investigated the effect of rubber coverings on concrete floors and the effect of 3 levels of dietary zinc supplementation on locomotion and claw and skin lesions in group-housed sows. Six groups of 21 +/- 4 hybrid sows were monitored during 3 successive reproductive cycles. The sows were group housed from d 28 after insemination (d 0) until 1 wk before expected farrowing date (d 108) in pens with either exposed concrete floors or concrete floors covered with rubber in part of the lying area and the fully slatted area. During each reproductive cycle, locomotion and skin lesions were assessed 4 times (d 28, 50, 108, and 140) and claw lesions were assessed twice (d 50 and 140). Results are given as least squares means +/- SE. Locomotion and claw scores were given in millimeters, on analog scales of 150 and 160 mm, respectively. Here, we report on the effect of floor type, which did not interact with dietary zinc concentration (P > 0.10 for all variables). At move to group (d 28) and mid gestation (d 50), no differences between floor treatments were seen in locomotion (P > 0.10). At the end of gestation (d 108), sows housed on rubber flooring scored 9.9 +/- 4.1 mm better on gait (P < 0.001). Regarding claw disorders, both parameters "heel overgrowth and erosion" (difference of 4.6 +/- 1.8 mm; P = 0.01) and "heel-sole crack" (difference of 3.1 +/- 1.5 mm; P = 0.04) scores were better for sows on rubber flooring at mid gestation (d 50). However, sows on rubber flooring scored worse for "vertical cracks in the wall horn" (difference of 3.4 +/- 1.7 mm; P = 0.04). At the end of lactation (d 140), both "white line" (difference of 2.9 +/- 1 mm; P = 0.02) and "claw length" (difference of 4.7 +/- 1.4 mm; P < 0.001) had better scores on rubber flooring. No differences for skin lesions were observed between floor treatments. The improved scores for gait toward the end of gestation and some types of claw disorders at mid gestation suggest that rubber flooring in group housing has a beneficial effect on the overall leg health of sows. The documented increase in vertical cracks in the wall horn at d 50 requires further investigation.

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An inverse source problem for a damped wave equation with memory

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Birthweight has no influence on chemical body composition and muscle energy stores in suckling piglets

Economic losses in pig production are highly due to neonatal mortality and poor postnatal growth performances predominantly of low birthweight piglets. To explore underlying mechanisms, we describe in this paper the effects of age and birthweight on body composition and muscle energy stores. Different parameters were assessed in pairs of low birthweight (LBW, n = 32) and normal birthweight (NBW, n = 32) piglets, at Day 0 (n = 16), Day 3 (n = 16), Day 10 (n = 16) and Day 28 (n = 16) of age. In total six piglets (three LBW and three NBW) per age group were killed for chemical total body composition analysis. The M. semimembranosus of 10 additional piglets (five LBW and five NBW) per age group were sampled for the analysis of muscle lipid and glycogen contents. Fore none of the tested parameters differences related to birthweight were observed (P > 0.05). With increasing age, dry matter, fat and protein percentages increased in both LBW and NBW piglets (P < 0.01). Body ash content remained constant during growth (P > 0.05). Muscle glycogen contents decreased with increasing age for both types of piglets (P < 0.05), whereas no age effects could be observed for muscle lipid deposition (P > 0.05). In conclusion, the age of the suckling piglet has a major impact on its body composition and muscle energy stores but its birthweight unexpectedly has no influence.

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Field experience with surgical castration with anaesthesia, analgesia, immunocastration and production of entire male pigs: performance, carcass traits and boar taint prevalence

Male piglets are castrated to reduce boar taint and also to reduce aggressive and sexual behaviour. However, the procedure as traditionally performed is painful and negatively affects performance. Large-scale results about the consequences of implementing alternatives on farms are lacking. We, therefore, investigated the practical applicability of the following five alternatives that can be implemented in the short term: surgical castration (1) without pain relief (CONT, control group), (2) with analgesia (MET, Metacam, 0.2 ml, 10 to 15 min before castration), (3) with general anaesthesia (CO2, inhalation, 100% CO2, 25 s, 3 l/min), (4) vaccination against boar taint (IM, two injections with Improvac) and (5) production of entire males (EM). The study consisted of the following two trials: (1) an experimental farm trial with 18 animals/treatment and (2) a large field trial on 20 farms with similar to 120 male pigs/farm per treatment and all treatments performed on each farm. Performance results as well as data on carcass traits, boar taint (hot-iron method) and testes development and weight were collected in both trials. Neither castration nor administration of analgesia or anaesthesia had an effect on daily gain of the piglets in the farrowing crates (P>0.05). Farmer records indicated that mortality in the farrowing crates (1.1%), nursery pens (1.8%) and fattening stable (2.2%) was not influenced by MET or CO2 compared with EM, IM or CONT (P>0.05). No significant differences were found for daily gain (P>0.05) nor slaughter age (P>0.05). Immunocastrates and EM had a better gain-to-feed ratio (P<0.05) compared with the groups of barrows (CONT, MET and CO2). Lean meat percentage was higher for EM compared with the barrows, and intermediate for IM (P<0.05). Carcass yield was lowest for IM (P<0.05). The hot-iron method indicated that boar taint was eliminated in barrows and IM compared with EM (P<0.001). Average prevalence of strong boar taint was 3% for EM, but varied from 0% to 14% between farms. As the effect of treatment on performance as well as the level of boar taint of EM was farm dependent, farmers should be encouraged to pre-test the different alternatives in order to make a well-considered choice for the best practical and profitable alternative for their farm.

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Effect of summer conditions and shade on behavioural indicators of thermal discomfort in Holstein dairy and Belgian Blue beef cattle on pasture

Using behavioural indicators of thermal discomfort, that is, shade seeking, panting scores (PS) and respiration rate (RR), we evaluated the effect of hot summer conditions and shade, for a herd of adult Holstein dairy cows and a herd of Belgian Blue beef cows kept on pasture in a temperate area (Belgium). During the summer of 2012, both herds were kept on pasture without access to shade (NS). During the summers of 2011 and 2013 each herd was divided into one group with (S) and one without (NS) access to shade. Shade was provided by young trees with shade cloth (80% reduction in solar radiation) hung between them. For S cows, we investigated how shade use was related to hot conditions as quantified by six climatic indices. The heat load index (HLI), which incorporates air temperature and humidity, solar radiation and wind speed, was the best predictor of the six indices tested. In 2011, there was a relatively high threshold for use of shade. When HLI = 90, shade use probability reached 17% for dairy cows and 27% for beef cows. In 2013, however, at HLI = 90, shade use probability reached 48% for dairy cows and 41% for beef cows. For animals from the NS treatment we determined the effect of hot summer conditions on RR and PS (with 0 = no panting and 4.5 = extreme panting). In both types of cattle, an increase in black globe temperature was the best predictor for increasing RR and PS. Furthermore, we determined how the effect of hot summer conditions on RR and PS was affected by the use of shade. Under hot conditions (black globe temperature >= 30 degrees C), >50% of the animals under shade retained normal PS and RR (PS < 1 and RR < 90 breaths per minute), whereas normal RR and PS were significantly less prevalent for animals outside shade. Our findings suggest that, even in temperate summers, heat can induce thermal discomfort in cattle, as evidenced by increases in shade use, RR and PS, and that shade increases thermal comfort.

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Olmutinib: First Global Approval

Abstract

Olmutinib (Olita^TM) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by Boehringer Ingelheim and Hanmi Pharmaceutical Co. Ltd for the treatment of non-small cell lung cancer (NSCLC). Third-generation EGFR TKIs with covalent binding to the receptors demonstrate irreversible enzymatic inhibition of activating EGFR mutations and T790M mutation (a common reason for acquired EGFR TKI resistance), while sparing wild-type EGFR. In December 2015, olmutinib was granted breakthrough therapy designation in NSCLC by the US FDA. In May 2016, olmutinib received its first global approval in South Korea for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. This article summarizes the milestones in the development of olmutinib leading to this first approval.

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Actively but not passively synchronized motor activity amplifies predictive timing

Publication date: 1 October 2016
Source:NeuroImage, Volume 139
Author(s): Nadine Conradi, Cornelius Abel, Stefan Frisch, Christian A. Kell, Jochen Kaiser, Maren Schmidt-Kassow
Previous studies have shown that the effect of temporal predictability of presented stimuli on attention allocation is enhanced by auditory-motor synchronization (AMS). The present P300 event-related potential study (N=20) investigated whether this enhancement depends on the process of actively synchronizing one's motor output with the acoustic input or whether a passive state of auditory-motor synchrony elicits the same effect. Participants silently counted frequency deviants in sequences of pure tones either during a physically inactive control condition or while pedaling on a cycling ergometer. Tones were presented either at fixed or variable intervals. In addition to the pedaling conditions with fixed or variable stimulation, there was a third condition in which stimuli were adaptively presented in sync with the participants' spontaneous pedaling. We replicated the P300 enhancement for fixed versus variable stimulation and the amplification of this effect by AMS. Synchronization performance correlated positively with P300 amplitude in the fixed stimulation condition. Most interestingly, P300 amplitude was significantly reduced for the passive synchronization condition by adaptive stimulus presentation as compared to the fixed stimulation condition. For the first time we thus provide evidence that it is not the passive state of (even perfect) auditory-motor synchrony that facilitates attention allocation during AMS but rather the active process of synchronizing one's movements with external stimuli.



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