The Naming Assessment in Multicultural Europe (NAME): Development and Validation in a Multicultural Memory Clinic.

OBJECTIVE: Traditional naming tests are unsuitable to assess naming impairment in diverse populations, given the influence of culture, language, and education on naming performance. Our goal was therefore to develop and validate a new test to assess naming impairment in diverse populations: the Naming Assessment in Multicultural Europe (NAME). METHOD: We carried out a multistage pilot study. First, we generated a list of 149 potentially suitable items - e.g. from published cross-linguistic word lists and other naming tests - and selected those with a homogeneous age of acquisition and word frequency across languages. We selected three to four colored photographs for each of the 73 remaining items; 194 controls selected the most suitable photographs. Thirteen items were removed after a pilot study in 15 diverse healthy controls. The final 60-item test was validated in 39 controls and 137 diverse memory clinic patients with subjective cognitive impairment, neurological/neurodegenerative disease or psychiatric disorders in the Netherlands and Turkey (mean age: 67, SD: 11). Patients were from 15 different countries; the majority completed primary education or less (53%). RESULTS: The NAME showed excellent reliability (Spearman-Brown coefficient: 0.95; Kuder-Richardson coefficient: 0.94) and robust correlations with other language tests (ρ = .35-.73). Patients with AD/mixed dementia obtained lower scores on most (48/60) NAME items, with an area under the curve of 0.88. NAME scores were correlated with age and education, but not with acculturation or sex. CONCLUSIONS: The NAME is a promising tool to assess naming impairment in culturally, educationally, and linguistically diverse individuals.

Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia.

Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND-but not WL-were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25-0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD.

Impaired Knowledge of Social Norms in Dementia and Psychiatric Disorders: Validation of the Social Norms Questionnaire-Dutch Version (SNQ-NL).

The Social Norms Questionnaire-Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer's dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations.

Exploring Abstract Semantic Associations in the Frontotemporal Dementia Spectrum in a Dutch Population.

OBJECTIVE: To investigate the differential ability of the "Test Relaties Abstracte Concepten" (TRACE), a Dutch test for abstract semantic knowledge, in frontotemporal dementia (FTD). METHODS: The TRACE was administered in patients with behavioral variant FTD (bvFTD; n = 16), nonfluent variant (nfvPPA; n = 10), logopenic variant (lvPPA; n = 10), and semantic variant primary progressive aphasia (svPPA; n = 9), and controls (n = 59). We examined group differences, performed correlational analyses with other neuropsychological tests and investigated discriminative ability. We compared the TRACE with a semantic association test for concrete stimuli (SAT). RESULTS: All patient groups, except nfvPPA, performed worse on the TRACE than controls (p < .01). svPPA patients performed worse than the other patient groups (p < .05). The TRACE discriminated well between patient groups, except nfvPPA, versus controls (all p < .01) and between svPPA versus other patient groups with high sensitivity (75-100%) and specificity (86%-92%). In bvFTD and nfvPPA the TRACE correlated with language tests (ρ > 0.6), whereas in svPPA the concrete task correlated (ρ ≥ 0.75) with language tests. Patients with bvFTD, nfvPPA and lvPPA performed lower on the TRACE than the SAT (p < .05), whereas patients with svPPA were equally impaired on both tasks (p = .2). DISCUSSION: We demonstrated impaired abstract semantic knowledge in patients with bvFTD, lvPPA, and svPPA, but not nfvPPA, with svPPA patients performing worse than the other subtypes. The TRACE was a good classifier between each patient group versus controls and between svPPA versus other patient groups. This highlights the value of incorporating semantic tests with abstract stimuli into standard neuropsychological assessment for early differential diagnosis of FTD subtypes.

Classical Correlation Model of Resonance Raman Spectroscopy.

A classical correlation model (CCM), based on forces instead of potentials, is developed and applied to resonance Raman scattering to provide a foundation for further advances in understanding the effects of fields and vibronic perturbations on the optical properties of materials by a simple, yet versatile, description. The model consists of a charge connected by a classical spring to a surface and driven by an external electric field. The spring represents the charge cloud of the electrons and the transition strength, and the surface represents the nucleus or molecule. Molecular vibrations are assumed to be many-body effects that change the configuration and hence modify the spring constant directly, as opposed to all previous classical models of Raman scattering, and opposed to the anisotropic bond model (ABM) of nonlinear optics, by adding anharmonic terms to the potential. The resulting expression agrees exactly with quantum mechanical models of resonance Raman scattering in the limit of weak electron-phonon coupling, and it agrees well when the coupling becomes strong. The result is a classical derivation of Kramers-Heisenberg-Dirac scattering theory. We show that the difference between classical and quantum approaches lies only in the interpretation of the prefactor. In particular, the Raman excitation profile shows excellent agreement with all other methods of calculation. By comparing complementary classical and quantum solutions of the same complex system, understanding of both is enhanced.

Differences in Discriminability and Response Bias on Rey Auditory Verbal Learning Test Delayed Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

OBJECTIVE: Episodic memory is impaired in Alzheimer's disease (AD) dementia but thought to be relatively spared in behavioral variant frontotemporal dementia (bvFTD). This view is challenged by evidence of memory impairment in bvFTD. This study investigated differences in recognition memory performance between bvFTD and AD. METHOD: We performed a retrospective analysis on the recognition trial of the Rey Auditory Verbal Learning Test in patients with bvFTD (n = 85), AD (n = 55), and control participants (n = 59). Age- and education-adjusted between-group analysis was performed on the total score and indices of discriminative ability and response bias. Correlations between recognition and measures of memory, language, executive functioning, and construction were examined. RESULTS: Patients with AD had a significantly lower total recognition score than patients with bvFTD (control 28.8 ± 1.5; bvFTD 24.8 ± 4.5; AD 23.4 ± 3.6, p < .01). Both bvFTD and AD had worse discriminative ability than controls (A' control 0.96 ± 0.03; bvFTD 0.87 ± 0.03; AD 0.84 ± 0.10, p < .01), but there was no difference in response bias (B" control 0.9 ± 0.2; bvFTD 1.6 ± 1.47; AD 1.4± 1.4, p < .01). AD had worse discriminability than bvFTD (p < .05). Discriminability was associated with memory for both patient groups (median correlation coefficient r = .34) and additionally associated with language (r = .31), but not executive functioning (r = -.03) in bvFTD. Response bias was unrelated to other cognitive functions (r = -.02). CONCLUSIONS: Discriminability, but not response bias, differentiated patients with bvFTD from AD. The presence of an impaired discrimination index suggests a "pure" (recognition) memory deficit in bvFTD.

Visit patterns at primary care centres and individual blood pressure level - a cross-sectional study.

OBJECTIVE: Hypertension is a major cause of cardiovascular disease. Nevertheless, blood pressure (BP) is often inadequately treated. We studied visit patterns at primary health care centres (PHCCs) and their relation to individual BP control. DESIGN AND SETTING: Cross-sectional register-based study on all patients with hypertension who visited 188 PHCCs in a Swedish region. PATIENTS: A total of 88,945 patients with uncomplicated hypertension age 40-79. MAIN OUTCOME MEASURES: Odds ratio (OR) for the individual patient to achieve the BP target of ≤140/90 mmHg. RESULTS: Overall, 63% of patients had BP ≤ 140/90 mmHg (48% BP < 140/90). The PHCC that the patient was enrolled at and, as part of that, more nurse visits at PHCC level was associated with BP control, adjusted OR 1,10 (95% CI 1.01 to 1.21). Patients visiting PHCCs with the highest proportion of visits with nurses had an even higher chance of achieving the BP target, OR 1.19 (95% CI 1.07 to 1.32). CONCLUSIONS: In a Swedish population of patients with hypertension, about half do not achieve recommended treatment goals. Organisation of PHCC and team care are known as factors influencing BP control. Our results suggests that a larger focus on PHCC organisation including nurse based care could improve hypertension care.

Pay for performance associated with increased volume of medication reviews but not with less inappropriate use of medications among the elderly - an observational study.

OBJECTIVE: A pay for performance programme was introduced in 2009 by a Swedish county with 1.6 million inhabitants. A process measure with payment linked to coding for medication reviews among the elderly was adopted. We assessed the association with inappropriate medication for five years after baseline. DESIGN AND SETTING: Observational study that compared medication for elderly patients enrolled at primary care units that coded for a high or low volume of medication reviews. PATIENTS: 144,222 individuals at 196 primary care centres, age 75 or older. MAIN OUTCOME MEASURES: Percentage of patients receiving inappropriate drugs or polypharmacy during five years at primary care units with various levels of reported medication reviews. RESULTS: The proportion of patients with a registered medication review had increased from 3.2% to 44.1% after five years. The high-coding units performed better for most indicators but had already done so at baseline. Primary care units with the lowest payment for coding for medication reviews improved just as well in terms of inappropriate drugs as units with the highest payment - from 13.0 to 8.5%, compared to 11.6 to 7.4% and from 13.6 to 7.2% vs 11.8 to 6.5% for polypharmacy. CONCLUSIONS: Payment linked to coding for medication reviews was associated with an increase in the percentage of patients for whom a medication review had been registered. However, the impact of payment on quality improvement is uncertain, given that units with the lowest payment for medication reviews improved equally well as units with the highest payment.

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10-year follow-up.

AIMS: To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. METHODS: We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. RESULTS: Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c , BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. CONCLUSIONS: People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.

Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.

The coupling of tautomerization to hydration in the transition state on the pyrimidine photohydration reaction path.

The ground state reaction path for formation of the pyrimidine hydrates was calculated using a nudged elastic band (NEB) approach, combined with a calculation of the transition state, and implemented using a numerical basis set in the density functional theory (DFT) code DMol(3). The model systems used for study consist of 1-methyl pyrimidines with a H2O molecule as the reactant, and the corresponding C5-hydro-C6-hydroxypyrimidine as the product. The barrier to addition of water across the C5-C6 π-bond ranges from 43-48 kcal mol(-1) in the 1-methylpyrimidines (1-MP) studied. Similar but slightly smaller barriers of 34-45 kcal mol(-1) were found for the tautomers of the 1-MPs, i.e. the enols of uridine and thymine and imine of cytosine. Comparison of these calculations with previous computational and experimental work suggests that a hot ground state formed by the rapid internal conversion of pyrimidines has sufficient energy to permit crossover from the common form to the tautomeric form of the pyrimidine at the transition state. The hot ground state mechanism can account for the experimentally observed yield and thermal reversion of pyrimidine photohydrates, while simultaneously explaining the effect of photohydrates on the mutation rate.

[Aortic aneurysm 2012: open, hybrid or total endovascular repair?]. / Aortenaneurysma 2012 - offen, hybrid oder total endovaskulär?

During the past two decades, minimally invasive endovascular procedures have changed therapeutic strategies. Such techniques have now become the method of choice for practically all vascular and aortic pathologies. This development is especially apparent in the treatment of aortic aneurysms. The purpose of this report is to provide a critical review about the current standard of care of abdominal and thoracic aorta based on an electronic Medline literature search. For elective infrarenal aneurysms, endovascular aneurysm repair (EVAR) has become a widely accepted alternative to open repair in cases with appropriate morphology. Currently, fenestrated (FEVAR) or branched endografts offer promising short- and mid-term results in juxtarenal aneurysms, however, these techniques are complex, technically challenging, and expensive. The alternative chimney or sandwich graft technique are becoming more common because they are feasible using standard endografts. Thoracic endovascular aortic repair (TEVAR) is already the gold standard for some descending pathologies. Complex thoracoabdominal aneurysms still require open surgery in centres of excellence, whereby, total endovascular repair or hybrid procedures have proved to be feasible in such specialist centres for selected patients.

Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes.

AIMS/HYPOTHESIS: Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes. METHODS: Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment. RESULTS: Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 µl/min), increased proteinuria (21 ± 2 vs 14 ± 1, µg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 µm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 ± 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD). CONCLUSIONS/INTERPRETATION: db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.

Risk factors for haemorrhage during local intra-arterial thrombolysis for lower limb ischaemia.

Assessment of clinical risk factors for haemorrhagic complications in patients undergoing intra-arterial thrombolysis for lower limb ischaemia. Retrospective reviews of consecutive patients subjected to intra-arterial thrombolysis due to lower limb ischemia at the Vascular Center, Malmö University Hospital, during a 5-year period from 2001 to 2005. Two hundred and twenty intra-arterial thrombolytic procedures were carried out in 195 patients (46% women), median age 73 years. Haemorrhagic complications were recorded in 72 procedures (33%), of which 13 were discontinued. Haemorrhage at the introducer and distant sites occurred in 53 and 32 procedures, respectively. Thrombolysis for occluded synthetic grafts was associated with higher risk of haemorrhage (P = 0.043). The platelet count was lower (P = 0.017) and the dose of alteplas higher (P = 0.041) in bleeders than in non-bleeders. Age was not associated with haemorrhage (P = 0.30). Two patients died during thrombolysis, one of them due to intracerebral haemorrhage. The grade of thrombolysis was an independent predictor of both in-hospital amputation (P < 0.001; OR 3.5 [95% CI 2.1-5.8]) and mortality (P = 0.021; OR 3.0 [95% CI 1.2-7.9]). The in-hospital amputation-free survival rate was 85% (188/220). Haemorrhage associated with thrombolysis is common, but does seldom require discontinuation of treatment. Insertion of introducers for local thrombolysis through synthetic grafts, lower platelet count and higher alteplas dose were found to be risk factors for haemorrhage. An algorithm for clinical management of haemorrhage has been proposed.

Ab initio calculation of resonance Raman cross sections based on excited state geometry optimization.

A method for the calculation of resonance Raman cross sections is presented on the basis of calculation of structural differences between optimized ground and excited state geometries using density functional theory. A vibrational frequency calculation of the molecule is employed to obtain normal coordinate displacements for the modes of vibration. The excited state displacement relative to the ground state can be calculated in the normal coordinate basis by means of a linear transformation from a Cartesian basis to a normal coordinate one. The displacements in normal coordinates are then scaled by root-mean-square displacement of zero point motion to calculate dimensionless displacements for use in the two-time-correlator formalism for the calculation of resonance Raman spectra at an arbitrary temperature. The method is valid for Franck-Condon active modes within the harmonic approximation. The method was validated by calculation of resonance Raman cross sections and absorption spectra for chlorine dioxide, nitrate ion, trans-stilbene, 1,3,5-cycloheptatriene, and the aromatic amino acids. This method permits significant gains in the efficiency of calculating resonance Raman cross sections from first principles and, consequently, permits extension to large systems (>50 atoms).

X-ray structure of the metcyano form of dehaloperoxidase from Amphitrite ornata: evidence for photoreductive dissociation of the iron-cyanide bond.

X-ray crystal structures of the metcyano form of dehaloperoxidase-hemoglobin (DHP A) from Amphitrite ornata (DHPCN) and the C73S mutant of DHP A (C73SCN) were determined using synchrotron radiation in order to further investigate the geometry of diatomic ligands coordinated to the heme iron. The DHPCN structure was also determined using a rotating-anode source. The structures show evidence of photoreduction of the iron accompanied by dissociation of bound cyanide ion (CN(-)) that depend on the intensity of the X-ray radiation and the exposure time. The electron density is consistent with diatomic molecules located in two sites in the distal pocket of DHPCN. However, the identities of the diatomic ligands at these two sites are not uniquely determined by the electron-density map. Consequently, density functional theory calculations were conducted in order to determine whether the bond lengths, angles and dissociation energies are consistent with bound CN(-) or O(2) in the iron-bound site. In addition, molecular-dynamics simulations were carried out in order to determine whether the dynamics are consistent with trapped CN(-) or O(2) in the second site of the distal pocket. Based on these calculations and comparison with a previously determined X-ray crystal structure of the C73S-O(2) form of DHP [de Serrano et al. (2007), Acta Cryst. D63, 1094-1101], it is concluded that CN(-) is gradually replaced by O(2) as crystalline DHP is photoreduced at 100 K. The ease of photoreduction of DHP A is consistent with the reduction potential, but suggests an alternative activation mechanism for DHP A compared with other peroxidases, which typically have reduction potentials that are 0.5 V more negative. The lability of CN(-) at 100 K suggests that the distal pocket of DHP A has greater flexibility than most other hemoglobins.

Nosocomial hepatitis C in a thoracic surgery unit; retrospective findings generating a prospective study.

We describe the transmission of hepatitis C virus (HCV) to two patients from a thoracic surgeon who was unaware of his hepatitis C infection. By partial sequencing of the non-structural 5B gene and phylogenetic analysis, the viruses from both patients were found to be closely related to genotype 1a strain from the surgeon. Two further hepatitis C cases were found in relation to the thoracic clinic. Their HCV sequences were related to each other but were of genotype 2b and the source of infection was never revealed. To elucidate the magnitude of the problem, we conducted a prospective study for a period of 17 months in which patients who were about to undergo thoracic surgery were asked to participate. Blood samples were drawn prior to surgery and at least four months later. The postoperative samples were then screened for anti-HCV and, if positive, the initial sample was also analysed. The only two patients (0.4%) identified were confirmed anti-HCV positive before surgery, and none out of 456 evaluable cases seroconverted to anti-HCV during the observation period. Despite the retrospectively identified cases, nosocomial hepatitis C is rare in our thoracic unit. The study points out the risk of transmission of hepatitis C from infected personnel and reiterates the need for universal precautions.

CO vibration as a probe of ligand dissociation and transfer in myoglobin.

We report femtosecond visible pump, midinfrared probe, spectrally integrated experiments resolving the dynamics of CO in myoglobin upon photodissociation. Our results show a progressive change in absorption strength of the CO vibrational transition during its transfer from the heme to the docking site, whereas the vibrational frequency change is faster than our time resolution. A phenomenological model gives good qualitative agreement with our data for a time constant of 400 fs for the change in oscillator strength. Density-functional calculations demonstrate that indeed vibrational frequency and absorption strength are not linearly coupled and that the absorption strength varies in a slower manner due to charge transfer from the heme iron to CO.

Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours.

BACKGROUND: Midgut carcinoid tumours often present with widespread disease making curative surgery impossible. Medical treatment therefore plays a major role in the treatment of these patients. METHODS: In this prospective randomized study, the effect of interferon (IFN) alpha on survival and risk of tumour progression was evaluated in 68 patients with midgut carcinoid tumours metastatic to the liver. All patients had undergone primary surgical treatment and hepatic arterial embolization of liver metastases before randomization. Patients were randomized to treatment with either octreotide alone (n = 35) or octreotide in combination with IFN-alpha (n = 33). RESULTS: Forty-one of the 68 patients died during a follow-up period of 33-120 months, equivalent to a 5-year survival rate of 46.5 per cent. There was no significant difference in survival between patients treated with octreotide alone (5-year survival rate 36.6 per cent) and those given octreotide in combination with IFN-alpha (56.8 per cent). However, patients treated with IFN-alpha had a significantly reduced risk of tumour progression during follow-up (P = 0.008). CONCLUSION: Addition of IFN-alpha to octreotide may retard tumour growth in patients with midgut carcinoid tumours.

Center for Synchrotron Biosciences' U2B beamline: an international resource for biological infrared spectroscopy.

A synchrotron infrared (IR) beamline, U2B, dedicated to the biomedical and biological sciences has been constructed and is in operation at the National Synchrotron Light Source (NSLS) of Brookhaven National Laboratory. The facility is operated by the Center for Synchrotron Biosciences of the Albert Einstein College of Medicine in cooperation with the NSLS. Owing to the broadband nature of the synchrotron beam with brightness 1000 times that of conventional sources, Fourier transform IR spectroscopy experiments are feasible on diffraction-limited sample areas at high signal-to-noise ratios and with relatively short data-acquisition times. A number of synchrotron IR microscopy experiments that have been performed in the mid-IR spectral range (500-5000 cm(-1)) are summarized, including time-resolved protein-folding studies in the microsecond time regime, IR imaging of neurons, bone and other biological tissues, as well as imaging of samples of interest in the chemical and environmental sciences. Owing to the high flux output of this beamline in the far-IR region (50-500 cm(-1)), investigations of hydrogen bonding and dynamic molecular motions of biomolecules have been carried out from 10 to 300 K using a custom-made cryostat and an evacuated box. This facility is intended as an international resource for biological IR spectroscopy fully available to outside users based on competitive proposal.