Challenges in modelling the reaction chemistry of interstellar dust.

Studies aiming to understand the physicochemical properties of interstellar dust and the chemical reactions that occur on and in it have traditionally been the preserve of astronomical observation and experimental attempts to mimic astronomically relevant conditions in the laboratory. Increasingly, computational modelling in its various guises is establishing a complementary third pillar of support to this endeavour by providing detailed insights into the complexities of interstellar dust chemistry. Inherently, the basis of computational modelling is to be found in the details (e.g. atomic structure/composition, reaction barriers) that are difficult to probe accurately from observation and experiment. This bottom-up atom-based theoretical approach, often itself based on deeper quantum mechanical principles, although extremely powerful, also has limitations when systems become too large or complex. In this Perspective, after first providing a general background to the current state of observational-based knowledge, we introduce a number of computational modelling methods with reference to recent state-of-the-art studies, in order to highlight the capabilities of such approaches in this field. Specifically, we first outline the use of computational chemistry methods for dust nucleation, structure, and individual reactions on bare and icy dust surfaces. Later, we review kinetic modelling of networks of reactions relevant to dust chemistry and how to take into account quantum tunnelling effects in the low temperature reactions in the interstellar medium. Finally, we point to the future challenges that need to be overcome for computational modelling to provide even more detailed and encompassing perspectives on the nature and reaction chemistry of interstellar dust.

Communication: On the stability of ice 0, ice i, and I(h).

Using ab initio methods, we examine the stability of ice 0, a recently proposed tetragonal form of ice implicated in the homogeneous freezing of water [J. Russo, F. Romano, and H. Tanaka, Nat. Mater. 13, 670 (2014)]. Vibrational frequencies are computed across the complete Brillouin Zone using Density Functional Theory (DFT), to confirm mechanical stability and quantify the free energy of ice 0 relative to ice I(h). The robustness of this result is tested via dispersion corrected semi-local and hybrid DFT, and Quantum Monte-Carlo calculation of lattice energies. Results indicate that popular molecular models only slightly overestimate the stability of ice zero. In addition, we study all possible realisations of proton disorder within the ice zero unit cell, and identify the ground state as ferroelectric. Comparisons are made to other low density metastable forms of ice, suggesting that the ice i structure [C. J. Fennel and J. D. Gezelter, J. Chem. Theory Comput. 1, 662 (2005)] may be equally relevant to ice formation.

Large variation of vacancy formation energies in the surface of crystalline ice.

Resolving the atomic structure of the surface of ice particles within clouds, over the temperature range encountered in the atmosphere and relevant to understanding heterogeneous catalysis on ice, remains an experimental challenge. By using first-principles calculations, we show that the surface of crystalline ice exhibits a remarkable variance in vacancy formation energies, akin to an amorphous material. We find vacancy formation energies as low as ~0.1-0.2 eV, which leads to a higher than expected vacancy concentration. Because a vacancy's reactivity correlates with its formation energy, ice particles may be more reactive than previously thought. We also show that vacancies significantly reduce the formation energy of neighbouring vacancies, thus facilitating pitting and contributing to pre-melting and quasi-liquid layer formation. These surface properties arise from proton disorder and the relaxation of geometric constraints, which suggests that other frustrated materials may possess unusual surface characteristics.

Improving the early presentation of cancer symptoms in disadvantaged communities: putting local people in control.

BACKGROUND AND AIMS: Premature deaths from cancer affect deprived communities disproportionately. The Department of Health has funded a programme in 19 Spearhead PCTs, delivered by the Improvement Foundation, to promote the early presentation and diagnosis of breast, bowel and lung cancers, with the ultimate intention of improving outcomes. METHODS: The programme uses improvement methodology and is a unique approach involving local people working in partnership in their communities to raise awareness of cancer symptoms and promote early presentation. The teams work with primary care, other statutory organisations and with the voluntary sector. The specific contribution of the local people has been in the identification of hard-to-reach groups and the tailoring of effective health messages. RESULTS: Interim results show an increase in the number of urgent 2-week referrals and the proportion of new cancer cases diagnosed through the urgent 2-week referral route (from 43% to 51%) for all three cancers. These results were statistically significant for the bowel cancer and lung cancer pathways. There was also an increase in the proportion with no spread at the time of diagnosis for bowel cancer (38-43%) and breast cancer (41-44.5%), but these results did not reach statistical significance. DISCUSSION: This programme, helping community volunteers to lead work on raising awareness and promotion of earlier presentation of cancer symptoms in partnership with primary care and other professionals, is delivering positive early results.

The phase diagram of water at negative pressures: virtual ices.

The phase diagram of water at negative pressures as obtained from computer simulations for two models of water, TIP4P/2005 and TIP5P is presented. Several solid structures with lower densities than ice Ih, so-called virtual ices, were considered as possible candidates to occupy the negative pressure region of the phase diagram of water. In particular the empty hydrate structures sI, sII, and sH and another, recently proposed, low-density ice structure. The relative stabilities of these structures at 0 K was determined using empirical water potentials and density functional theory calculations. By performing free energy calculations and Gibbs-Duhem integration the phase diagram of TIP4P/2005 was determined at negative pressures. The empty hydrates sII and sH appear to be the stable solid phases of water at negative pressures. The phase boundary between ice Ih and sII clathrate occurs at moderate negative pressures, while at large negative pressures sH becomes the most stable phase. This behavior is in reasonable agreement with what is observed in density functional theory calculations.

Liver abscess secondary to an endoscopic tattoo in the colon.

Introduction Endoscopic tattooing of colonic lesions has been used safely for their localization. CASE HISTORY We report a 61-year-old female who had left hemicolectomy in 2006 for adenocarcinoma of the left colon (pT3, pN0, M0). Cancer in the transverse colon was discovered during annual colonoscopy surveillance. The lesion was tattooed 5cm proximal to the lesion. Twenty-four days after tattooing, she was admitted to the emergency department with increased levels of inflammatory markers. CT showed an abscess in the left lobe of the liver adjacent to the tattoo site. The abscess was drained under ultrasound guidance. She had antibiotic treatment for 3 weeks and made a full recovery. CONCLUSION Endoscopic tattooing of colonic lesions is safe but this case report highlights the possibility of a rare (but serious) complication that must be taken into consideration.

Electronic clinical trial protocol distribution via the World-Wide Web: a prototype for reducing costs and errors, improving accrual, and saving trees.

Clinical trials today typically are inefficient, paper-based operations. Poor community physician awareness of available trials and difficult referral mechanisms also contribute to poor accrual. The Physicians Research Network (PRN) web was developed for more efficient trial protocol distribution and eligibility inquiries. The Medical University of South Carolina's Hollings Cancer Center trials program and two community oncology practices served as a testbed. In 581 man-hours over 18 months, 147 protocols were loaded into PRN. The trials program eliminated all protocol hardcopies except the masters, reduced photocopier use 59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage PRN. There were no known security breaches, downtime, or content-related problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method for distributing protocols and reducing distribution errors and delays because only a single copy of each protocol is maintained. Furthermore, PRN is being extended to serve other aspects of trial operations.

Detection of arboviral RNA directly from mosquito homogenates by reverse-transcription-polymerase chain reaction.

Many arthropod-borne viruses (arboviruses) are important human pathogens medically. The development of an effective technique to detect the viruses by using nucleic acid amplification, such as polymerase chain reaction (PCR), improves not only clinical diagnosis but also virologic surveillance of mosquito vectors in the field. In this study, the development of an improved and simplified assay is described for detection of mosquitoes infected with eastern equine encephalitis (EEE) virus, Cache Valley (CV), and California (CAL) serogroup viruses from field-collected mosquito pools. As little as 5 microl of homogenate from mosquito pools was used in the reverse transcription (RT) reaction followed by the use of three sets of specific primers for the PCR. Positive pools were determined by finding PCR bands of the expected size for each arbovirus. The confirmation and identification of Bunyaviruses was done by sequencing the PCR product. In 1999, West Nile virus (WNV) was identified as the etiologic agent of an outbreak of human encephalitis in New York City. It is shown that this protocol is also able to detect West Nile viral RNA in a pool of 100 mosquitoes containing one infected mosquito.

The effect of psychological strategies upon cardiorespiratory and muscular activity during treadmill running.

Twelve aerobically trained males (age 22 +/- 1.3 yr, range 18-31) were studied to determine the effects of VE and EMG feedback upon cardiorespiratory and muscular activity during one segment of a continuous 36-min bout of treadmill running just below ventilatory threshold (VT). Ventilatory, metabolic, cardiovascular, RPE, and EMG variables recorded during a 12-min feedback segment were compared with those observed during 12-min attentional distraction and control conditions. The three treatments were counterbalanced. Mean VO2 (2987 ml.min-1) remained constant across the three periods as did VCO2 (3102 ml.min-1), HR (168 bpm), RQ (0.95), and O2 pulse (18.5 ml.beat-1). However, VE was significantly reduced during feedback (Fb) as compared with both the distraction (D) and control (C) conditions (mean +/- SE: 83.2 +/- 3.6 vs 86.6 +/- 4.2 and 87.8 +/- 4.2 l.min-1, respectively). This effect was marked by a reduction in respiratory rate (RR) (41.1 +/- 2.1 vs 44.5 +/- 1.9 and 46.8 +/- 1.9 breaths.min-1 for Fb, D, and C, respectively) and an increase in tidal volume (TV) (2115 +/- 144 vs 1904 +/- 110 and 2020 +/- 102 ml.breath-1 for Fb, D, and C, respectively). These changes resulted in significant reductions in VE/VO2 (26.5 +/- 0.7 vs 28.9 +/- 1.0 and 28.3 +/- 0.9 ratio magnitudes), VE/VO2 (28.1 +/- 0.8 vs 30.2 +/- 1.0 and 29.7 +/- 1.0 ratio magnitudes), and PETO2 (105.5 +/- 1.0 vs 108.4 +/- 1.1 and 107.6 +/- 1.2 mm Hg) during Fb as compared with D and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of a semi-quantitative adolescent food frequency questionnaire applied at a public school in São Paulo, Brazil.

OBJECTIVE: To develop a food frequency questionnaire for adolescents (AFFQ) and demonstrate its relative validity. DESIGN: The final version of the AFFQ was composed of 76 food items previously identified according to their contribution in nutrients and overall importance within the eating habits of this population group. The validation study, which was undertaken during a 6 month period (June to November 1999), was administered to a sample of 79 who answered at least three 24 h dietary recalls (R24 h) applied at intervals of 45 days and one AFFQ at the end of the study. Applying the paired t-test and calculating Pearson correlation coefficients on nutrient data, differences in the mean of nutrients were obtained. Correlation coefficients between the mean energy-adjusted nutrients computed by the two methods were calculated, and correction was made for within-person variability. Agreement was evaluated by distribution of the adolescents according to quartiles of consumption. LOCUS: A public school within the metropolitan region of São Paulo city. RESULTS: A high variability in the dietary intake of adolescents was observed, with high rates of variability for cholesterol, retinal and vitamin C. The Pearson correlation coefficients, after being adjusted and corrected for variability, ranged from 0.10 to 0.72 among females and from 0.16 and 0.91 among males. The mean correlation coefficient for the entire group was 0.52. CONCLUSIONS: These results indicate that the AFFQ provides a potentially reliable scale for categorizing individuals by level of past intake of most nutrients, excluding retinol and iron.

pH-metric log P. 4. Comparison of partition coefficients determined by HPLC and potentiometric methods to literature values.

The pKa and log P of 20 compounds, including six substituted phenols, two substituted quinolines, N-methylaniline, five barbiturate derivatives, two phenothiazines, and several other molecules of pharmaceutical interest, were determined by the potentiometric technique at 25 degrees C and ionic strength 0.1 M (KNO3). The log P values were determined also by partition HPLC. Three of the substances were of very low aqueous solubility, and for these the aqueous pKas were determined by extrapolation from methanol-water solutions using the Yasuda-Shedlovsky technique. Values of log P obtained both by potentiometry and by partition HPLC, which ranged from 0.3 to 5.4, were in very good acordance with literature values. The general applicability of the potentiometric technique to ionizable compounds of diversely varied structures was demonstrated by the study.

Freeze-preserved vein grafts and atherosclerosis. An experimental study.

Histopathological changes of three types of vein grafts were studied. Freeze-preserved, fresh human grafts and autografts were inserted as patches in the aorta of rabbits on regular and variable cholesterol diets. In all grafts the endothelium and adventitia were reconstituted after a few months. In the wall, smooth muscle and elastic tissue were markedly diminished and poorly oriented with accompanied collagenisation. Cholesterol diet led to progressive fat and/or calcium deposition with subintimal proliferation in the autografts and fresh xenografts. In contrast this was seen to a much lesser degree and later in freeze preserved xenografts, even on higher cholesterol diets. Deep freezing considerably reduces the cellularity of the graft and its metabolic ability to accumulate lipids. Freeze-preserved veins seem to be a suitable graft for vascular reconstructions in severely atherosclerotic patients and compare favorably with vein autografts.

The fate of the freeze-preserved xenograft: an experimental study on rabbits, cats, and dogs.

Freeze-preserved allografts have been used successfully in patients for vascular peripheral replacement, dialysis, and chemotherapy. Freezing of veins seems to decrease or abolish antigenicity by decreasing the viable cellular components of the grafts. To confirm its acceptance and consequently, the high patency rates of freeze-preserved vein grafts, we inserted segments of human veins preserved at -80 degrees Centigrade as arterial substitutes into rabbits, cats, and dogs and studied the morphological changes of these xenografts up to 2 years. In all the groups, the patency rate was satisfactory. In rabbits and dogs, the cellular inflammatory reaction around the grafts and suture lines disappeared after a few weeks; the endothelium was reconstructed at 2 months and a poorly differentiated cellular fibro-collagenous wall with prominent hyalin matrix was observed. In cats, however, the histio-lymphocytic infiltrate persisted in functioning grafts up to 2 years associated with adjacent prominent vascular and nerve proliferation. It is suggested that this inflammatory reaction has no deleterious effect on the graft; on the contrary, it promotes its neovascularisation and innervation. The cat proved to be a good animal model for vascular surgical experiments. Our study proved the poor antigenicity of freeze-preserved venous xenograft. It could, in the future, be used for human arterial substitutes.

Continuity of care on admission to hospital: an audit of Airedale NHS Trust's transfer policy.

Describes an audit of interprofession communications among hospital, community health and social services concerning hospital admission. Information from 150 patient admissions (50 from each of three general practices after a target date) was gathered from both community and hospital sources. The results were used to audit the transfer policy operated by Airedale NHS Trust. The audit design incorporated an element of research, the results of which were used to inform the interpretation of the audit results and to suggest appropriate recommendations for change. Recommendations included the introduction of a pre-admissions checklist, specific changes to the nursing documentation, measures to improve the speed of information transfer, and the clarification of responsibilities for initiating contact across the hospital-community interface when patients with existing contacts in community services are admitted to hospital. Concludes that the introduction of supplementary research to an otherwise traditional audit cycle strengthened the resulting recommendations.

Evidence for layer-specific differences in auditory corticocollicular neurons.

Recent data suggest that there may be distinct processing streams emanating from auditory cortical layers 5 and 6 that influence the auditory midbrain. To determine whether these projections have different physiological properties, we injected rhodamine-tagged latex tracer beads into the inferior colliculus of >30-day-old mice to label these corticofugal cells. Whole-cell recordings were performed on 62 labeled cells to determine their basic electrophysiological properties and cells were filled with biocytin to determine their morphological characteristics. Layer 5 auditory corticocollicular cells have prominent I(h)-mediated sag and rebound currents, have relatively sluggish time constants, and can generate calcium-dependent rhythmic bursts. In contrast, layer 6 auditory corticocollicular cells are non-bursting, do not demonstrate sag or rebound currents and have short time constants. Quantitative analysis of morphology showed that layer 6 cells are smaller, have a horizontal orientation, and have very long dendrites (>500 µm) that branch profusely both near the soma distally near the pia. Layer 5 corticocollicular cells are large pyramidal cells with a long apical dendrite with most branching near the pial surface. The marked differences in physiological properties and dendritic arborization between neurons in layers 5 and 6 make it likely that each type plays a distinct role in controlling auditory information processing in the midbrain.