Metastability of diamond ramp-compressed to 2 terapascals.

Carbon is the fourth-most prevalent element in the Universe and essential for all known life. In the elemental form it is found in multiple allotropes, including graphite, diamond and fullerenes, and it has long been predicted that even more structures can exist at pressures greater than those at Earth's core1-3. Several phases have been predicted to exist in the multi-terapascal regime, which is important for accurate modelling of the interiors of carbon-rich exoplanets4,5. By compressing solid carbon to 2 terapascals (20 million atmospheres; more than five times the pressure at Earth's core) using ramp-shaped laser pulses and simultaneously measuring nanosecond-duration time-resolved X-ray diffraction, we found that solid carbon retains the diamond structure far beyond its regime of predicted stability. The results confirm predictions that the strength of the tetrahedral molecular orbital bonds in diamond persists under enormous pressure, resulting in large energy barriers that hinder conversion to more-stable high-pressure allotropes1,2, just as graphite formation from metastable diamond is kinetically hindered at atmospheric pressure. This work nearly doubles the highest pressure at which X-ray diffraction has been recorded on any material.

Best practice guidelines in the psychosocial management of HPV-related head and neck cancer: recommendations from the European Head and Neck Cancer Society's Make Sense Campaign.

Over the past three decades, oral human papillomavirus (HPV) has been associated with an increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) in several countries. Specialist oncologists in head and neck cancer are observing a wider range of demographics, sexual behaviours, and survival outcomes with their patients. Additionally, there are fewer smokers, consumers of alcohol, or people of lower socioeconomic status than in previous decades. In order to support patients, the European Head and Neck Society's Make Sense Campaign aims to promote best practice in the management of head and neck cancer through the delivery of counselling, psychological assessment, support with the patient experience following HPV-related cancer diagnosis, sexual impact (in terms of communication, behaviour and prevention), facilitating access to educational resources about HPV in head and neck squamous cell carcinoma and OPSCC, and early referral if necessary. New concerns about psychosocial distress and unmet psychosocial needs following diagnosis, therefore, exist throughout the disease and treatment periods. Oncologists treating patients with HPV-related head and neck cancer must integrate new parameters focused on infection risk transmission and sexual topics. The development and dissemination of best practice guidelines through The European Head and Neck Cancer Society Make Sense Campaign will help healthcare professionals to be more confident and resourceful in supporting patients with HPV-related head and neck cancer.

Best practices in the management of the psycho-oncologic aspects of head and neck cancer patients: recommendations from the European Head and Neck Cancer Society Make Sense Campaign.

Squamous cell carcinoma of the head and neck (SCCHN) is considered a worldwide health care problem. The majority of patients have a history of alcohol abuse and high-level tobacco consumption; however, SCCHN is also associated with exposure to viruses including human papillomavirus (HPV) and Epstein-Barr virus. A major problem facing SCCHN patients is that their disease is often diagnosed at an advanced stage where treatment options may not be curative, or can have severe post-treatment consequences. Confronted with their diagnosis and treatment options, the patient can express a range of emotional reactions which may lead to maladaptive coping. During the SCCHN patient journey, there are a number of stages where emotional support could be offered. A point of contact should be allocated to help patients navigate these stages and deliver practical emotive support (such as encouraging attendance at hospital appointments, compliance with lifestyle modifications and treatment adherence), and to identify if or when more advanced emotive support, in the form of a mental health professional, might be needed. This role might be carried out by a representative within the multidisciplinary health care team (e.g. a nurse). While optimal care is provided by specialist health care professionals, each with specific roles and responsibilities during the patient journey, all are important in screening for emotional distress and providing referral to the mental health team. This article reviews the key points for delivering emotional support to SCCHN patients at each stage of their care. Emotional problems cannot be ignored in SCCHN patients if optimal outcomes are to be achieved, particularly as therapeutic options extend overall survival for many patients. Health care professionals must be able to implement efficient screening for psychological distress to support patient's compliance to their care and treatment. They must also be able to recognize when to refer patients at risk for pharmacological and/or psychotherapeutic interventions.

Time-resolved X-ray diffraction diagnostic development for the National Ignition Facility.

We present the development of an experimental platform that can collect four frames of x-ray diffraction data along a single line of sight during laser-driven, dynamic-compression experiments at the National Ignition Facility. The platform is comprised of a diagnostic imager built around ultrafast sensors with a 2-ns integration time, a custom target assembly that serves also to shield the imager, and a 10-ns duration, quasi-monochromatic x-ray source produced by laser-generated plasma. We demonstrate the performance with diffraction data for Pb ramp compressed to 150 GPa and illuminated by a Ge x-ray source that produces ∼7 × 1011, 10.25-keV photons/ns at the 400 µm diameter sample.

Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines.

BACKGROUND: Radiation dermatitis developing in patients receiving cetuximab concomitantly with radiotherapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is now recognized to have different pathophysiological and clinical characteristics to the radiation dermatitis associated with radiotherapy or concomitant chemotherapy and radiotherapy. Current grading tools were not designed to grade this type of radiation dermatitis; their use may lead to misclassification of reactions and inappropriate management strategies, potentially compromising cancer treatment. PATIENTS AND METHODS: An advisory board of seven leading European specialists (three medical oncologists, three radiation oncologists and a dermatologist) with extensive experience of the use of cetuximab plus radiotherapy produced consensus guidelines for the grading and management of radiation dermatitis in patients receiving cetuximab plus radiotherapy. RESULTS: Modifications to the current, commonly used National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.3 for grading radiation dermatitis were proposed. Updated management guidelines, building on previously published guidelines from 2008, were also proposed. CONCLUSIONS: The proposed revisions to the grading system and updated management guidelines described here represent important developments toward the more appropriate grading and effective management of radiation dermatitis in patients receiving cetuximab plus radiotherapy for LA SCCHN.

Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis.

During human immunodeficiency virus (HIV) infection there is a profound and selective decrease in the CD4+ population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4+ cells appear to be productively infected with HIV-1 in seropositive individuals. In the present study, crosslinking of bound gp120 on human CD4+ T cells followed by signaling through the T cell receptor for antigen was found to result in activation-dependent cell death by a form of cell suicide termed apoptosis, or programmed cell death. The data indicate that even picomolar concentrations of gp120 prime T cells for activation-induced cell death, suggesting a mechanism for CD4+ T cell depletion in acquired immune deficiency syndrome (AIDS), particularly in the face of concurrent infection and antigenic challenge with other organisms. These results also provide an explanation for the enhancement of infection by certain antibodies against HIV, and for the paradox that HIV appears to cause AIDS after the onset of antiviral immunity.

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323).

BACKGROUND: The EORTC 24971/TAX 323, a phase III study of 358 patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck, showed an improved progression-free and overall survival (OS) with less toxicity when docetaxel (T) was added to cisplatin and 5-fluorouracil (PF) for induction and given before radiotherapy (RT). The impact of the addition of docetaxel on patients' health-related quality of life (HRQOL) and symptoms was investigated. METHODS: HRQOL was assessed at baseline, at end of cycle 2, and 4, 6, and 9 months after completion of RT using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (EORTC QLQ-H&N35). The primary HRQOL scale was global HRQOL per protocol. RESULTS: Compliance to HRQOL assessments was 97% at baseline, but dropped to 54% by 6 months. Data were analysed up to 6 months. There was a trend towards improved global HRQOL during the treatment period. At 6 months after the end of RT, global HRQOL was higher in the TPF arm than in the PF arm, but the low compliance does not allow to draw definitive conclusions. Swallowing and coughing problems decreased more in the TPF arm than in the PF arm at the end of cycle 2, but to a limited extent. CONCLUSION: Induction chemotherapy with TPF before RT not only improves survival and reduces toxicity compared with PF but also seems to improve global HRQOL in a more sustainable manner.

Viscous Rayleigh-Taylor instability experiments at high pressure and strain rate.

Experimental results showing significant reductions from classical in the Rayleigh-Taylor instability growth rate due to high pressure effective lattice viscosity are presented. Using a laser created ramped drive, vanadium samples are compressed and accelerated quasi-isentropically at approximately 1 Mbar peak pressures, while maintaining the sample in the solid state. Comparisons with simulations and theory indicate that the high pressure, high strain rate conditions trigger a phonon drag mechanism, resulting in the observed high effective lattice viscosity and strong stabilization of the Rayleigh-Taylor instability.

Transcriptome analysis of Schistosoma mansoni larval development using serial analysis of gene expression (SAGE).

SUMMARY: Infection of the snail, Biomphalaria glabrata, by the free-swimming miracidial stage of the human blood fluke, Schistosoma mansoni, and its subsequent development to the parasitic sporocyst stage is critical to establishment of viable infections and continued human transmission. We performed a genome-wide expression analysis of the S. mansoni miracidia and developing sporocyst using Long Serial Analysis of Gene Expression (LongSAGE). Five cDNA libraries were constructed from miracidia and in vitro cultured 6- and 20-day-old sporocysts maintained in sporocyst medium (SM) or in SM conditioned by previous cultivation with cells of the B. glabrata embryonic (Bge) cell line. We generated 21 440 SAGE tags and mapped 13 381 to the S. mansoni gene predictions (v4.0e) either by estimating theoretical 3' UTR lengths or using existing 3' EST sequence data. Overall, 432 transcripts were found to be differentially expressed amongst all 5 libraries. In total, 172 tags were differentially expressed between miracidia and 6-day conditioned sporocysts and 152 were differentially expressed between miracidia and 6-day unconditioned sporocysts. In addition, 53 and 45 tags, respectively, were differentially expressed in 6-day and 20-day cultured sporocysts, due to the effects of exposure to Bge cell-conditioned medium.

Differences in splanchnic metabolism between late gestation and early lactation dairy cows.

In the transition from the pre- to postcalving state, the demands on the cow increase from support of gestation to high rates of milk production. This extra demand is met partly by increased intake but may also involve altered metabolism of major nutrients. Six multiparous Holstein cows were used to monitor changes in net fluxes of nutrients across the portal-drained viscera and liver (splanchnic tissues) between late gestation and early lactation. Blood samples were obtained simultaneously from the portal, hepatic, and subcutaneous abdominal veins and the caudal aorta 18 d before expected calving and 21 or 42 d after calving. On the day of blood sampling and the 3 d preceding sampling, cows were fed every 2 h. The precalving (1.63 Mcal of net energy for lactation/kg and 1,326 g of metabolizable protein/d) and postcalving (1.72 Mcal of net energy for lactation/kg and 2,136 g of metabolizable protein/d) diets were based on corn silage, alfalfa hay, and corn grain. Dry matter intake increased postcalving. Net splanchnic release of glucose increased postpartum because of tendencies for both increased portal absorption and net liver release. Increased removal of lactate, rather than AA, contributed to the additional hepatic gluconeogenesis. Although portal absorption of AA increased with intake at the onset of lactation, hepatic removal of total AA-N tended to decline. This clearly indicates that liver removal of AA is not linked to portal absorption. Furthermore, net liver removal relative to total liver inflow even decreased for Gly, His, Met, Phe, and Tyr. Together, these data indicate that in early lactation, metabolic priority is given to direct AA toward milk protein production rather than gluconeogenesis, in cows fed a corn-based ration.

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck.

BACKGROUND: Radiation dermatitis occurs to some degree in most patients receiving radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma of the head and neck (SCCHN) who receive radiotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may develop a characteristic acne-like rash in addition to dermatitis. DESIGN: An advisory board of 11 experienced radiation oncologists, medical oncologists and dermatologists discussed the management options for skin reactions in patients receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was categorised according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3) grading. RESULTS: Both general and grade-specific approaches for the management of dermatitis in this patient group are presented. It was concluded that where EGFR inhibitor-related acne-like rash and dermatitis coexist within irradiated fields, management should be based on the grade of dermatitis: for grade 1 (or no dermatitis), treatment recommendations for EGFR-related acne-like rash outside irradiated fields should be followed; for grades 2 and above, treatment recommendations for dermatitis were proposed. CONCLUSIONS: This paper presents comprehensive consensus guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR inhibitors in combination with radiotherapy.

Effects of physiological concentrations of heavy metals both individually and in mixtures on the viability and function of peripheral blood human leukocytes in vitro.

Among environmental contaminants recognized for their toxicity and global distribution, heavy metals are elements known to exert serious ecological consequences. Published experiments on the immunotoxic effects of metals such as methylmercury (MeHg), cadmium (Cd), and lead (Pb) were often conducted at concentrations higher than those present in the environment or those in human blood. In the present study the in vitro effects on human blood of environmentally relevant concentrations of MeHg (33-200 mug/L), Cd (3.1-16 mug/L), and Pb (75-207 mug/L) were assessed individually and in mixtures on the viability and immune competence of peripheral blood leukocytes (PBLs). At MeHg concentrations of 120 and 200 mug/L both lymphocyte proliferation, as measured by [(3)H]thymidine incorporation, and natural killer (NK) cytotoxity activity, as determined by dioctadecyloacarbocyanine, were suppressed. Our results showed an increase of intracellular thiols in lymphocytes and in monocytes at all the concentrations of metals tested. A decrease in the level of metallothionein (MT) was seen in monocytes in presence of Hg at concentration of 120 mug/L and higher. For lymphocytes, a significant increase of MT in groups containing the lower concentrations of Cd, and Hg was noted. In summary, it appears that Hg represents the most toxic metal at environmentally relevant concentrations on human peripheral mononuclear cells. The effects of Hg exposure were greater on lymphocytes and NK cells than on monocytes.

Effects of reduced dietary calcium and phytase supplementation on calcium and phosphorus utilisation in broilers with modified mineral status.

1. The impact of modified mineral status and dietary Ca:P ratio on Ca and P utilisation was measured in chicks with or without phytase supplementation. 2. In a preliminary study, 4 diets were given to chicks from 3 to 15 d of age: D1 (6.5 g P/kg and Ca:P = 1.5) and D2, D3 and D4 (6.0, 5.4 and 5.0 g P/kg, respectively, and Ca:P = 1.2). Growth performance was similar across diets. Tibia ash was similar in chicks given D1 and D2, but was gradually depressed from D2 to D4 (-22%). 3. In the depletion period, two groups of chicks, with similar performance, but with different mineral status were achieved by feeding them, from 5 to 15 d of age, diets with a similar Ca:P ratio of 1.2, but containing 6.3 or 5.2 g P/kg. 4. During the subsequent 11 d of the repletion period, chicks from each of the two previous groups were given one of the 4 diets containing 5.7 g P/kg, but differing in their Ca (8.3 and 5.3 g Ca/kg) and microbial phytase (0 or 1000 FTU, Natuphos levels in a 2 x 2 x 2 factorial arrangement. 5. At the end of the repletion period, the initially depleted chicks could not be differentiated from the non-depleted chicks, indicating the capacity of chicks to compensate for their initial depleted mineral status. 6. Interaction between dietary Ca and phytase levels was not significant. Phytase improved growth performance and bone characteristics. Reduced dietary Ca enhanced feed intake and growth rate, but depressed bone dry matter and ash weight. 7. At the end, diets supplemented with phytase maximised bone ash weight when chicks were fed with a Ca:P ratio of 1.5 but elicited the highest growth rate when chicks were fed with a Ca:P ratio of 0.9.

Consequences of dietary calcium and phosphorus depletion and repletion feeding sequences on growth performance and body composition of growing pigs.

The effect of a calcium (Ca) and phosphorus (P) depletion and repletion strategy was studied in four consecutive feeding phases of 28 days each. In all, 60 castrated male pigs (14±1.6 kg initial BW) received 60% (low (L) diet; depletion) or 100% (control (C) diet; repletion) of their Ca and digestible P requirements according to six feeding sequences (CCCC, CCCL, CLCC, CCLC, LCLC and LLLL; subsequent letters indicate the diet received in phases 1, 2, 3 and 4, respectively). Pigs bone mineral content in whole-body (BMCb) and lumbar vertebrae L2 to L4 (BMCv) was measured in every feeding phase by dual-energy X-ray absorptiometry. Growth performance was slightly (<10%) affected by depletion, however, dietary treatments did not affect overall growth. Compared with control pigs, depletion reduced BMCb (34%, 38%, 33% and 22%) and BMCv (46%, 54%, 38% and 26%) in phases 1 to 4, respectively. Depletion increased however digestible P retention efficiency from the second to the fourth phases allowing LLLL pigs to present no differences in BMCb and BMCv gain compared with CCCC pigs in phase 4. Growth performance in repleted compared with control pigs was lower in phase 2, was no different in phase 3 and was lower in CLCC pigs in phase 4. Repletion increased body P and Ca retention efficiency when compared with control pigs (respectively, 8% and 10% for LC v. CC, P<0.01; 8% and 10% for CLC v. CCC, P<0.10; 18% and 25% for CLCC, CCLC, LCLC v. CCCC, P<0.001). Moreover, BMCv gain was higher in CLC pigs (P<0.001) and gains of body P, Ca, BMCb and BMCv in phase 4 were also higher in repleted than in CCCC pigs (respectively, 14%, 20%, 20% and 52%; P⩽0.02). Repletion reduced body P, Ca, BMCb and BMCv masses in phase 2 but no differences were found in phase 4 compared with control pigs. Lumbar vertebrae L2 to L4 bone mineral content was more sensitive to depletion and repletion sequences than BMCb especially in the first phase probably due to a higher proportion of metabolically active trabecular bone in vertebrae than in the whole skeleton. Dietary Ca was, however, oversupply in L compared with C diets (3.1 v. 2.5 Ca:digestible P ratio, respectively) suggesting that P has probably driven the regulations. Phosphorus and Ca depletion and repletion increases dietary P utilization efficiency and can help to reduce dietary P supply, but the underlying mechanisms need elucidation before its practical application.

Oncology for medical students: a European School of Oncology contribution to undergraduate cancer education.

Worldwide undergraduate cancer medicine is taught in a non-unanimous manner. There are frequent overlaps, omissions and discrepancies in the curricula of different medical schools concerning oncology teaching. Various attempts for possible changes and improvements have been made. Several extra-curriculum teaching programmes have been developed in academic European settings in collaboration with other scientific bodies. In this paper, we are analyzing the educational results from 115 medical students--mostly Europeans--who participated in three Oncology Summer Courses (2004, 2005, 2006) organized by European School of Oncology in collaboration with the University of Ioannina.

Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study).

The effects of a chronic load of nonabsorbable sugars on intracolonic bacterial metabolism of carbohydrates and on H2 breath excretion are disputed. However, most of the discussion relies on indirect evidence or on results of in vitro studies. Thus, we attempted to assess directly and in vivo the effects on intracolonic metabolism of lactulose of a chronic oral load of this nonabsorbable disaccharide. 20 g of lactulose was given orally twice daily during 8 d to eight normal volunteers. In all, breath H2 concentration was measured on days 1 and 8 after ingestion of the morning lactulose dose. In four subjects, stools were collected during 2 d at the beginning and at the end of the lactulose maintenance period to measure fecal pH and daily outputs of carbohydrates and beta-galactosidase. The four other subjects were intubated on days 1 and 8 to measure the pH and the concentrations of carbohydrates, lactic acid, and volatile fatty acids (VFA) in the distal ileum and cecal contents. Moreover, 14C-lactulose was added to cold lactulose and 14CO2 breath outputs determined. Pulmonary H2 excretion fell from day 1 to day 8 (P less than 0.05), whereas 14CO2 excretion increased (P less than 0.01). Fecal water pH, lactic acid, and VFA concentrations did not vary between the two stool collection periods. 24-h fecal weight, fecal water, and carbohydrate outputs showed a trend to decrease between days 1 and 2 and days 7-8, whereas beta-galactosidase activity rose markedly (P less than 0.01). No significant variations were observed for all parameters measured in ileal fluid. In the cecum, areas under the concentration curves decreased from day 1 to day 8 for lactulose, galactose, and fructose (P less than 0.01), while an increase was found for lactic acid (P less than 0.001), acetic acid (P less than 0.0001), and total VFA (P less than 0.001). Cecal fluid pH dropped faster (P less than 0.05) and to a lower level (P less than 0.05) on day 8 than on day 1. These data clearly show that a chronic load of a nonabsorbable sugar induces changes in colonic bacterial metabolic pathways resulting in a better efficiency of the flora to digest the carbohydrate.

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck?

Radiotherapy remains the foundation of current treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). It has been shown that the addition of concurrent chemotherapy to radiotherapy (chemoradiotherapy, CRT, or chemotherapy-enhanced radiation therapy, CERT) results in improved clinical outcome in terms of both locoregional control and overall survival in some groups of patients. However, CRT is associated with severe, dose-limiting acute toxicities and, in some patients, a higher proportion of late toxicities. In addition, most CRT regimens are platinum-based and there is evidence that the maximum tolerable toxicity has been reached with the dose intensities currently used in bolus cisplatin regimens. Therefore, if we are to further improve outcomes through increased treatment compliance, more effective and more tolerable regimens are needed. Recent results from a phase III randomised study demonstrate that the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux)given concomitantly with radiotherapy yields a significant clinical benefit over radiotherapy alone without any increase in radiotherapy-associated toxicity. In this review, we explore the question of the degree to which adding cetuximab improves the efficacy of radiotherapy in locally advanced SCCHN and how the benefits of cetuximab plus radiotherapy compare with those achievable with CRT.

Effect of glutamine supplementation on splanchnic metabolism in lactating dairy cows.

The suggestion that glutamine (Gln) might become conditionally essential postpartum in dairy cows has been examined through increased postruminal supply of Gln. Net nutrient flux through the splanchnic tissues and mammary gland was measured in 7 multiparous Holstein cows receiving abomasal infusions of water or 300 g/d of Gln for 21 d in a crossover design. Milk yield increased significantly (by 3%) in response to Gln supplementation, but the 2.4% increase in milk protein yield was not statistically significant. Glutamine treatment had no effect on portal or hepatic venous blood flows. Net portal appearance of Gln and Glu was increased by Gln supplementation, accounting for 83% of the infused dose with, therefore, only limited amounts available to provide additional energy to fuel metabolism of the portal-drained viscera. The extra net portal appearance of Gln was offset, however, by a corresponding increase in hepatic removal such that net Gln splanchnic release was not different between treatments. Nonetheless, the Gln treatment resulted in a 43% increase in plasma Gln concentration. Infusions of Gln did not affect splanchnic flux of other nonessential amino acids or of essential amino acids. Glutamine supplementation increased plasma urea-N concentration and tended to increase net hepatic urea flux, with a numerical increase in liver hepatic O2 consumption. There were no effects on glucose in terms of plasma concentration, net portal appearance, net liver release, or postliver supply, suggesting that Gln supplementation had no sparing effect on glucose metabolism. Furthermore, mammary uptake of glucose and amino acids, including Gln, was not affected by Gln supplementation. In conclusion, this study did not support the hypothesis that supplemental Gln would reduce glucose utilization across the gut or increase liver gluconeogenesis or mammary glutamine uptake to increase milk protein synthesis.