Similar patterns of leaf temperatures and thermal acclimation to warming in temperate and tropical tree canopies.

As the global climate warms, a key question is how increased leaf temperatures will affect tree physiology and the coupling between leaf and air temperatures in forests. To explore the impact of increasing temperatures on plant performance in open air, we warmed leaves in the canopy of two mature evergreen forests, a temperate Eucalyptus woodland and a tropical rainforest. The leaf heaters consistently maintained leaves at a target of 4 °C above ambient leaf temperatures. Ambient leaf temperatures (Tleaf) were mostly coupled to air temperatures (Tair), but at times, leaves could be 8-10 °C warmer than ambient air temperatures, especially in full sun. At both sites, Tleaf was warmer at higher air temperatures (Tair > 25 °C), but was cooler at lower Tair, contrary to the 'leaf homeothermy hypothesis'. Warmed leaves showed significantly lower stomatal conductance (-0.05 mol m-2 s-1 or -43% across species) and net photosynthesis (-3.91 µmol m-2 s-1 or -39%), with similar rates in leaf respiration rates at a common temperature (no acclimation). Increased canopy leaf temperatures due to future warming could reduce carbon assimilation via reduced photosynthesis in these forests, potentially weakening the land carbon sink in tropical and temperate forests.

Neonatal extracorporeal membrane oxygenation: practice patterns and predictors of outcome in the UK.

OBJECTIVE: To review the UK neonatal extracorporeal membrane oxygenation (ECMO) service and identify predictors of outcome. DESIGN: Retrospective review of the national cohort. PATIENTS AND INTERVENTIONS: 718 neonates received ECMO for respiratory failure between 1993 and 2005. MEASUREMENTS AND RESULTS: Diagnoses were: 48.0% meconium aspiration syndrome (97.1% survivors), 15.9% congenital diaphragmatic hernia (CDH; 57.9% survivors), 15.9% sepsis (62.3% survivors), 9.5% persistent pulmonary hypertension (79.4% survivors), 5.6% respiratory distress syndrome (92.5% survivors) and 5.1% congenital lung abnormalities (24.3% survivors). The overall survival rate of 79.7% compared favourably with the worldwide Extracorporeal Life Support Organization (ELSO) Registry. Over the period of review, pre-ECMO use of advanced respiratory therapies increased (p<0.001), but ECMO initiation was not delayed (p = 0.61). The use of veno-venous (VV) ECMO increased (p<0.001) and average run time fell (p = 0.004). Patients treated with VV ECMO had a survival rate of 87.7% compared with 73.4% in the veno-arterial (VA) ECMO group; only 42.4% of those needing conversion from VV to VA ECMO survived. In non-CDH neonates, lower birth weight, lower gestational age, older age at ECMO and higher oxygenation index (OI) were associated with increased risk of death. In CDH neonates, lower birth weight and younger age at ECMO were identified as risk factors for death. CONCLUSION: The UK neonatal ECMO service achieves good outcomes and with overall survival rate reaching 80% compares favourably with international results. Advanced respiratory therapies are used widely in UK ECMO patients. Identification of higher OI and older age at ECMO as risk factors in non-CDH neonates reinforces the importance of timely referral for ECMO.

Random comparison of 'virtual patient' models in the context of teaching clinical communication skills.

AIMS: Two types of virtual patient designs can be distinguished: a 'narrative' structure and a 'problem-solving' structure. This study compares the same virtual patient with two different structures within the domain of communication skills. METHODS: Two virtual patients were constructed around the same case, one emphasizing a narrative and one a problem-solving model. Use of these packages was trialled with undergraduate medical students over 2 years. Students were randomly assigned to tutorials using the virtual patients, and their communication skills were compared with baseline performance by a separate group. Outcome was assessed by evaluation of an interview with a simulated patient. RESULTS: There was no significant difference between the three groups in overall communication skills. However there was a significant improvement in the communication skills of the narrative group when compared only with the problem-solving group. Additionally, various aspects of communication skills, such as use of open-ended questions and appropriate language, showed significant differences between the three groups. CONCLUSION: There is some evidence to support the value of a narrative design for virtual patients which are to be used to teach communication skills, which encourages further investigation.

Genetic risk of Alzheimer's disease: advising relatives.

BACKGROUND: Clinicians are increasingly asked by relatives of patients with Alzheimer's disease to advise on their genetic risk of developing Alzheimer's disease in later life. Many clinicians find this a difficult question to answer. AIMS: To provide information for old age psychiatrists wishing to advise relatives of their risk of developing Alzheimer's disease. METHOD: A selective review of the key literature on the genetic epidemiology of Alzheimer's disease. RESULTS: Currently a DNA diagnosis is attainable in some 70% of families with autosomal dominant Alzheimer's disease. In first-degree relatives of most cases, risk is increased some three- or four-fold relative to controls, but only one-third of this is realised in the average life span. Apolipoprotein E genotyping cannot be used as a predictive test and confers only minimal diagnostic benefit. CONCLUSIONS: Pedigrees with familial Alzheimer's disease should be referred to a Regional Centre for Medical Genetics. Accurate risk prediction is not possible in the vast majority of pedigrees with Alzheimer's disease, although it is possible for the psychiatrist to give a rough estimate of the risk, which can reasonably the couched in reassuring terms.

Structural features of a peptide corresponding to human kappa-casein residues 84-101 by 1H-nuclear magnetic resonance spectroscopy.

The peptide Val-Arg-Arg-Pro-Asn-Leu-His-Pro-Ser-Phe-Ile-Ala-Ile-Pro-Pro- Lys-Lys-Ile, which corresponds to residues 84-101 of human kappa-casein, has been synthesized and its conformation preferences determined by 1H-nuclear magnetic resonance spectroscopy in dimethyl sulphoxide. The peptide adopted a largely extended chain conformation in solution and there was evidence for the presence of a beta-turn involving residues Pro87-His90 of human kappa-casein. The presence of a turn in this position would make the physiologically significant Arg85 residue of human kappa-casein (which is equivalent to Arg97 in bovine kappa-casein) unavailable for interaction with Asp249 of bovine chymosin, and may partly explain why human kappa-casein is hydrolysed more slowly than its bovine counterpart by bovine chymosin.

Micelle stability: kappa-casein structure and function.

The stability of the casein micelle is dependent on the presence of kappa-casein (CN) on the surface of the micelle where it functions as an interface between the hydrophobic caseins of the micelle interior and the aqueous environment. kappa-Casein is also involved in thiol-catalyzed disulfide interchange reactions with the whey proteins during heat treatments and, after rennet cleavage, in the facilitation of micelle coagulation. These functions of kappa-CN are regulated by the three-dimensional structure of the protein on the micelle surface. The usual means of determining structure are not available for kappa-CN because this protein is strongly self-associating and has never been crystallized. Instead, algorithms were used to predict selected secondary structures and circular dichroism spectroscopy on kappa-CN and the macropeptide released by chymosin. Three peptides were synthesized to cover the chymosin-sensitive site (His98-Lys111), the region in the macropeptide that could be helical (Pro130-Ile153), and the region between. Nuclear magnetic resonance spectroscopy showed that the peptide His98-Lys111 was probably a beta-strand with tight turns at each end. This hypothesis was confirmed by a study of the molecular dynamics showing that the C variant of kappa-CN interacted less strongly with chymosin; consequently, the slow renneting time of milk that contains this protein was explainable. Both circular dichroism and nuclear magnetic resonance indicated that the peptide Pro130-Ile153 was probably helical under normal physiological conditions. A preliminary study using nuclear magnetic resonance showed that the intervening peptide had no discernible secondary structure. Consequently, most of the beta-sheet structure of kappa-CN is likely in the para-kappa-CN region.

Attitudes to and use of a modified prescription form by general practitioners and pharmacists.

OBJECTIVE: To evaluate the rate of use and acceptance of a new prescription form designed to provide more information to pharmacists and patients. DESIGN: Prospective descriptive study. SETTING: A semi-rural community outside Melbourne, Victoria, in November 1994. PARTICIPANTS: GPs and pharmacists working three or more sessions per week in the locality, and 21 consumers who formed two consumer focus groups. INTERVENTION: An education session for GPs and pharmacists, followed by a one-month trial of new prescription forms which included notations to facilitate interprofessional communication. MAIN OUTCOME MEASURES: Rate of use and acceptability of the new prescription notations. RESULTS: Eighteen GPs and 10 pharmacists participated; 3600 forms were issued and 2521 prescriptions, including 3464 prescription items, were analysed. GPs and pharmacists used at least one of the new prescription notations in 45% (1559) of prescription items; 35% of prescription items (1222) were notated with the general purpose of the medication. Qualitative findings suggested that GPs, pharmacists and consumers considered the new prescription form to be beneficial and useful. CONCLUSIONS: A modified prescription form to increase communication between GPs and pharmacists is acceptable in clinical practice.

Solution conformation of a peptide corresponding to bovine kappa-casein B residues 130-153 by circular dichroism spectroscopy and 1H-nuclear magnetic resonance spectroscopy.

The peptide Pro130-Thr-Ser-Thr-Pro-Thr-Ile-Glu-Ala-Val-Glu140- Ser-Thr-Val-Ala-Thr-Leu-GLu-Ala-Ser-Pro150-Glu-Val-Ile, which corresponds to residues 130-150 of kappa-casein B, was synthesized and the conformation of the peptide in solution investigated by circular dichroism (CD) spectroscopy, structure prediction algorithms and 1H-nuclear magnetic resonance spectroscopy. In a solution containing the structure-enhancing solvent trifluoroethanol the CD spectrum was typical of a peptide in the alpha-helical conformation and nuclear magnetic resonance showed that the amino acids between Ile136 and Ser149 (kappa-casein numbering) were predominantly in the alpha-helical conformation but that Pro130 to Thr135 and Pro150 to Ile153 were not. In addition, Thr133-Pro134 and Ser-149-Pro150 were primarily in the trans conformation, the residues from Thr131 to Thr135 were in unordered structures and the residues from Glu151 to Ile153 were in an extended conformation. Residues Glu137 to Glu140 and Thr145 to Ala148 also displayed some 3(10)-helix character. When the peptide was dissolved in 10 mM-cetyltrimethylammonium chloride solution at pH 6, the CD spectra indicated that the proportion of helical structure was comparable to that of the peptide in trifluoroethanol solution (400 ml/l), whereas when the peptide was dissolved in buffer alone in 10 mM-SDS solution, the CD spectra were consistent with a low helical content. Acidification of these solutions to pH 2.85 resulted in a slight increase in the helical content of the peptide in buffer and more markedly in buffer containing SDS. When the peptide was in 5 mM-CaCl2 solution at neutral pH, the CD spectrum indicated that some ordered structure was present. Taken together these results indicate that the ionizable residues Glu137, Glu140, Glu147 and Glu151 could be important in determining the stability of the putative helix. The structure predictions found that the sequence from Glu137 to Pro150 would be more likely to be in a helical than any other conformation in the intact bovine protein, but that pig, sheep and goat kappa-caseins did not give a prediction of a strongly helical region in this part of the molecule.

Association between a PS-1 intronic polymorphism and late onset Alzheimer's disease.

Previous work suggests an association between allele 1 and the 1-1 genotype of an intronic polymorphism in the presenilin-1 (PS-1) gene and late onset Alzheimer's disease. We found an excess of the 1-1 genotype in our late onset clinical sample (p = 0.006, one-tailed) but not in our postmortem confirmed sample, which instead exhibited an excess of allele 1 (p = 0.02, one-tailed). No interaction between PS-1 and ApoE genotype was detected and the findings remained significant when the effects of ApoE were taken into account (p = 0.03, one-tailed). These results suggest that the PS-1 polymorphism, or a locus in linkage disequilibrium with it, acts as a risk factor for late onset AD.

No evidence that common allelic variation in the Amyloid Precursor Protein (APP) gene confers susceptibility to Alzheimer's disease.

In order to test the hypothesis that allelic variation within the Amyloid Precursor Protein (APP) gene influences susceptibility to common forms of Alzheimer's disease (AD) we screened the entire coding, promoter and 3' untranslated sequences of the APP gene for DNA variations in 30 unrelated patients and eight controls with probable AD by a combination of RT-PCR PCR and chemical cleavage mismatch analysis. Although we were unable to detect commonly occurring allelic variants, we were able to detect a novel mutation within the APP gene in one individual with late-onset AD. This mutation resulted in the substitution of a tryptophan residue for an arginine residue at codon 328 within exon 7 which encodes the so-called protease inhibitor domain of the 751 residue APP isoform. However, the pathological significance of this mutation is uncertain as neither this, nor any other mutation occurring within exon 7 of the APP gene was found in any of a further 102 AD patients and 86 age-matched controls. In conclusion, it is unlikely that susceptibility to AD results from commonly occurring allelic variants of the APP gene and it is even less probable that mutations within exon 7 of the APP gene are important risk factors for late-onset AD.

General practitioners and pharmacists interprofessional communication.

This draft joint statement by the Royal Australian College of General Practitioners and the Pharmaceutical Society of Australia Ltd is published here for comment as a national initiative. All suggestions received will be considered before a final statement is adopted.

Confirmation of association between the e4 allele of apolipoprotein E and Alzheimer's disease.

The Apo E genotype of 86 patients with Alzheimer's disease (AD) and 77 age matched controls was determined by digestion of Apo E PCR products with the restriction enzyme CfoI. The frequency of the e4 allele was significantly increased in the patient group (0.33) as compared with controls (0.12). This effect was seen in patients with a family history and in sporadic cases. The odds ratio in homozygotes for the e4 allele was 11.24 (95% confidence interval 2.45-51.50). There was no relationship between age of onset and Apo E genotype. There was no linkage disequilibrium between the apolipoprotein E locus and a TaqI polymorphism at the Apo CII locus, and no allelic association between Apo CII and AD.

Mass mammographic screening--the other side of the argument.

National mammographic screening is being introduced in Australia for older women. Information about the programme and the research evidence in its favour was recently circulated to general practitioners. The material made no mention of deficiencies in the research evidence, nor of the potential negative consequences of screening. The author discusses these issues.