Increased Susceptibility to Aphids of Flowering Wheat Plants Exposed to Low Temperatures.

Frost is known to directly affect flowering wheat plants (Triticum aestivum L.) and lead to reduced grain yield. Additionally, it may increase wheat susceptibility to economically important pests, such as aphids (Hemiptera: Aphididae). Wheat plants at flowering stage were exposed to one of the three temperature treatments: ambient (11-12°C), 0°C, and -3°C for 60 min. Preference (3-choice) and performance (no-choice) bioassays with aphids (Rhopalosiphum padi L.) were conducted 1, 3, 6, and 12 d after temperature treatments to assess effects of temperature-induced stress over time. As an initial feasibility study of using remote sensing technologies to detect frost-induced stress in flowering wheat plants, hyperspectral imaging data were acquired from wheat plants used in preference bioassays. Element analysis of wheat plants was included to determine the effect of temperature-induced stress on the nutritional composition of flowering wheat plants. The results from this study support the following cause-effect scenario: a 60-min exposure to low temperatures caused a significant decrease in potassium and copper content of wheat plants 6 d after temperature exposure, and it coincided with a marked increase in preference by aphids of wheat plants. The preference exhibited by aphids correlated positively with performance of aphids, so the preference-performance hypothesis was confirmed and possibly driven by potassium and copper content of wheat plants. In addition, we demonstrated that hyperspectral imaging data can be used to detect frost-induced susceptibility to aphid infestation in flowering wheat plants. These findings justify further research into airborne remote sensing of frost-induced stress and the possible secondary effects on crop susceptibility to arthropod pests.

The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.

BACKGROUND: Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed. OBJECTIVE: Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients. DESIGN: Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. SETTING: Two hundred and seventy-four hospitals in 40 countries. PARTICIPANTS: Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury. INTERVENTIONS: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other. RESULTS: Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment (≤ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p < 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64. CONCLUSIONS: Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/). TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. FUNDING: The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.

Serum total testosterone is lower in men with Alzheimer's disease.

OBJECTIVES: The purpose of this study was to determine whether the level of serum total testosterone (TT) was different in cases of Dementia of the Alzheimer's Type (DAT) than in controls. SETTING AND DESIGN: We included 83 referred DAT cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford Project To Investigate Memory and Ageing. METHODS: Information was obtained about potential confounds in the relation of DAT with testosterone, including age, gender, education, body mass index, smoking, (ab)use of alcohol, diabetes mellitus, endocrine therapy, and having undergone hysterectomy. TT was measured in non-fasting serum obtained between 10 and 12 a.m. using a competitive enzyme immunoassay. RESULTS: Men with DAT (n=39) had lower levels (p =0.005) of total serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L). Lower TT was more likely in men with DAT, independent of potential confounds (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT levels between cases (n=44) and controls (n=62). MAIN FINDINGS: Our results suggested that low TT may be a co-morbid feature of DAT in men. However, low TT levels could also exacerbate the disease. CONCLUSIONS: Prospective longitudinal studies should investigate whether low TT levels precede or follow the onset of DAT (209 words).

Constructional apraxia in Alzheimer's disease: association with occipital lobe pathology and accelerated cognitive decline.

The functional impact and progression of occipital lobe pathology in sporadic late onset Alzheimer's disease (AD) is barely explored. It is accepted that the primary and association visual areas are affected relatively late, in the neocortical stages of AD. We analysed 60 prospectively assessed AD patients in whom global cognitive deterioration and constructional apraxia were evaluated longitudinally using the CAMDEX. Radioactive immunohistochemistry was used to assess the amount of AD-related pathology in Brodmann areas 18 and 17. Braak staging of each case was also carried out. This study showed that in AD patients constructional apraxia is associated with higher expression of hyperphosphorylated tau. Additionally our findings indicate that early constructional apraxia is a predictor of accelerated cognitive decline in AD.

A new visual rating scale for white matter low attenuation on CT.

The pathological substrate and clinical significance of white matter low density change on computed tomography (CT) remains incompletely understood, hampered by suboptimal rating scales. We developed a new scale and applied it to 647 CTs in 382 patients. White matter change was categorised by region (anterior and posterior frontal, parietal, occipital), severity (mild, moderate, severe) and extent (periventricular, extending to deep white, full thickness). Multiplying extent by severity gave regional scores, which were summated to give an overall score. CTs were read separately by 2 radiologists. Intraobserver reliabilities were 0.69 and 0.55, interobserver 0.70 (kappa values). Each assessment required only 1 min.

The use of aromatherapy in intrapartum midwifery practice an observational study.

The authors report the process and results of an evaluation of a midwifery aromatherapy service for mothers in labour: This study of 8058 mothers in childbirth, is the largest research initiative in the use of aromatherapy within a health-care setting. The study involved a wide range of participants, from mothers who experienced a low risk, spontaneous labour and birth, to those whose labour was induced, and those who had vaginal operative delivery and Caesarean section. The study-took place over a period of 8 years, which enabled a more challenging test of the effect of aromatherapy on intrapartum midwifery practice and outcomes. In the study a total of 10 essential oils were used, plus a carrier oil, which were administered to the participants via skin absorption and inhalation. The study found little direct evidence that the practice of aromatherapy per se reduces the need for pain relief during labour, or the incidence of operative delivery. But a key finding of this study suggests that two essential oils, clary sage and chamomile are effective in alleviating pain. The evidence from this study suggests that aromatherapy can be effective in reducing maternal anxiety, fear and/or pain during labour. The use of aromatherapy appeared to facilitate a further reduction in the use of systemic opioids in the study centre, from 6% in 1990 to 0.4% in 1997 (per woman). Aromatherapy is an inexpensive care option. In 1997 when 1592 mothers used aromatherapy, the total cost was 769.17 Pounds. The study reports a minimal incidence of associated symptoms. Out of 8058 mothers, 1% (100) recorded an associated symptom. These were mild in nature. The successful model of integrated practice that this aromatherapy study presents, offers a useful example for other units to consider.

Coexisting pathologies in the brain: influence of vascular disease and Parkinson's disease on Alzheimer's pathology in the hippocampus.

The finding of more than one coexisting brain pathology in dementia sufferers is not unusual. However, it is unclear how these different diseases may interact or influence the evolution of one another. In this study we analyse the hippocampal expression patterns of hyperphosphorylated tau, paired helical filament (PHF)-related protein, beta-amyloid and synaptophysin in a group of Alzheimer's disease (AD) sufferers with and without additional pathology. Compared to cases with only AD-type pathology we found that the presence of additional vascular disease augmented the accumulation of hyperphosphorylated tau in the CA1 region of the hippocampus without affecting PHF formation in cases with mild AD changes and reduced the extent of PHF formation in the CA2/3 and CA4 regions of the hippocampus in cases with severe AD pathology. We also found that synaptophysin immunoreactivity in the CA4 and dentate gyrus in pure AD was inversely related to the extent of amyloid accumulation but not to neurofibrillary pathology in the same regions. These relationships were lost when additional pathology was present. Memory scores obtained during life correlated closely with hyperphosphorylated tau and PHF-related protein expression in CA1 in pure AD but not in AD with additional pathology. Total amyloid and synaptophysin expression in the hippocampus did not correlate with memory scores in any patient group. Our findings suggest that the interactions of two pathologies in the hippocampus are complex and may differ depending on the stage reached in the evolution of a progressive disease such as AD.

An investigation into the use of aromatherapy in intrapartum midwifery practice.

OBJECTIVE: The principal aim of the study was to examine the contribution of aromatherapy to the promotion of maternal comfort during labor and as a tool to improve the quality of midwifery care. DESIGN: Evaluative study. SETTING: Delivery suite in a large British teaching hospital with approximately 6,500 deliveries per annum. SUBJECTS: A total of 8,058 mothers were evaluated between 1990 and 1998. INTERVENTIONS: Women were offered aromatherapy to relieve anxiety, pain, nausea and/or vomiting or to strengthen contractions. Routine data collected on the use of aromatherapy over the period were analyzed. Data from the unit audit were used to provide a comparison group of mothers not given aromatherapy (n = 15,799) from the study center. OUTCOME MEASURES: Outcome measures include mothers' ratings of effectiveness, outcomes of labor, use of pharmacologic pain relief, uptake of intravenous oxytocin, reported associated symptoms, and annual costs. RESULTS: The use of aromatherapy during childbirth was an increasingly popular care option with mothers and midwives. More than 50% of mothers rated it as helpful, and only 14% found it unhelpful. The use of aromatherapy was not confined to low-risk mothers. Sixty percent of the sample were primigravidae, and 32% overall had had their labor induced. The administration of aromatherapy in childbirth did appear to reduce the need for additional pain relief in a proportion of mothers. More than 8% of primigravidae and 18% of multigravidae used no conventional pain relief during labor after using essential oils. During the years of the study, the use of pethidine in the study center declined from 6% to 0.2% of women. The study also showed that aromatherapy may have the potential to augment labor contractions for women in dysfunctional labour. A very low number of associated adverse symptoms were reported (1%). CONCLUSION: This study represents a successful example of the integration of a complementary therapy into mainstream midwifery practice and forms a basis for future research.

Diagnosing dementia: interrater reliability assessment and accuracy of the NINCDS/ADRDA criteria versus CERAD histopathological criteria for Alzheimer's disease.

We investigated the interrater reliability and accuracy of two independent medical doctors in using NINCDS/ADRDA criteria to classify 82 elderly subjects enrolled in OPTIMA, a longitudinal study investigating dementia. Kappa statistics revealed moderate agreement (0.5) in overall classification of dementia type, and almost perfect agreement (0.9) on the absence or presence of dementia. Combining NINCDS/ADRDA 'possible' and 'probable' Alzheimer's disease (AD) categories produced substantial agreement (0.7). Comparison with CERAD histopathological criteria for AD showed that combining 'possible' and 'probable' AD resulted in a high sensitivity and accuracy, but a low specificity. To increase specificity, the NINCDS/ADRDA 'probable AD' category should be used alone. An important finding was that the accuracy of diagnoses of AD made from the case notes alone was not different from the diagnoses obtained following active involvement with participants.

Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease.

Cerebrovascular disease and Alzheimer's disease commonly occur together in the elderly and each may contribute to dementia. Here we present evidence that cerebrovascular disease significantly worsens cognitive performance in the earliest stages of Alzheimer's disease.

Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages': a prospective study.

The distribution of pathology related to Alzheimer's disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.

The progression of Alzheimer's disease from limbic regions to the neocortex: clinical, radiological and pathological relationships.

Alzheimer's disease (AD) is characterised by the gradual accumulation of neurofibrillary pathology in selected regions of the brain. Earlier studies indicate that the accumulation of neurofibrillary tangles is associated both with decline in patient's cognitive performance as well as with medial temporal lobe atrophy on CT scans. There are also indications that progression through the pathological stages of AD is associated with decline in cognitive functions. The results of this study indicate that progression of disease, especially beyond the boundaries of the limbic regions, is associated with marked decline in the cognitive performance of patients suffering from AD. However the clinical manifestations of early pathological stages are not so well defined. We also found that the atrophy of the medial temporal lobe on CT scans is related to the progression of pathology. Atrophy is most apparent when the disease reaches its isocortical stages and is not marked in the limbic stages of the disease. The additive effect of pathologies co-existing with AD is apparent in reduced cognitive scores, while the atrophy of limbic structures, as measured on CT scans, seems to be mainly attributable to AD-related pathology.

Comparison of pathological diagnostic criteria for Alzheimer disease.

Because the clinical picture of Alzheimer disease (AD) is often difficult to discriminate from other dementing illnesses, the diagnosis of AD requires neuropathological confirmation. However, for the pathological diagnosis of AD, there are no unanimously accepted criteria. The three currently used sets of pathological criteria (Khachaturian: Khachaturian, Arch Neurol 1985;42:1097-105; Tiemy: Tierney et al., Can J Neurol Sci 1986; 13:424-6; CERAD: Mirra et al., Neurology 1991;41:479-86) for the disease differ from each other considerably. We applied these criteria to the first 43 consecutive subjects (37 demented) with no neuropathology other than AD-type pathology from autopsies after longitudinal prospective clinical study in the Oxford Project to Investigate Memory and Ageing (OPTIMA). The results show that the CERAD category of definite AD corresponds closely with the cases that fulfill Tierney A3 inclusion criteria for AD. The combined CERAD categories of possible, probable, and definite AD correspond closely to cases fulfilling Khachaturian criteria forAD. The influence of a clinical diagnosis of dementia when Khachaturian and CERAD criteria were applied was considerable because between 9.3% and 90.7% of patients would have been categorized differently depending on whether clinical dementia was present or absent.

Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging.

In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m-hexamethyl-propylene amineoxime (99mTC-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49% sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both "probable-AD" and "possible-AD" was 61% specific, 96% sensitive, and 85% accurate. DSM-III-R criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases and including the 105 living, elderly controls, the diagnostic accuracy of the Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89% sensitivity, 80% specificity, and 83% accuracy; and the combination of the two was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74% sensitive but yielded 40% false positives in the histologically confirmed series. The diagnostic accuracy afforded by this method of CT and SPECT used alone is better than that of any established clinical criteria and reveals that the combination of MTL atrophy and parietotemporal hypoperfusion is common in AD, much less common in other dementias, and rare in normal controls. In the NINCDS-ADRDA criteria "possible-AD" cases, the combination of CT and SPECT findings alone were better in all diagnostic indices than the presence of Apo E4 alone in predicting AD. The frequent occurrence of MTL atrophy in AD and also in other "non-AD" dementias later in the course of the disease suggests the concept of medial temporal lobe dementia. This could explain some of the overlap of clinical profiles in the dementias, particularly as the dementia progresses, making clinical differential diagnosis difficult. In this context, the use of SPECT can significantl

Accuracy of clinical operational diagnostic criteria for Alzheimer's disease in relation to different pathological diagnostic protocols.

In this study we analysed the accuracy of two sets of clinical diagnostic criteria, the NINCDS/ADRDA and DSM-III-R, in relation to the currently used pathological diagnostic criteria for Alzheimer's disease (AD), the Khachaturian criteria, the Tierney A3 criteria and the CERAD protocol. The sensitivity of the individual clinical diagnostic criteria, NINCDS/ADRDA and DSM-III-R, is poor (34-58%) irrespective of the pathological diagnostic criteria applied for the definite diagnosis of AD. The combination of the NINCDS/ ADRDA 'possible' and 'probable dementia of the Alzheimer type' (DAT) categories has a high sensitivity (91-98%). However the combination resulted in very poor specificity (40-61 %). Thus, none of the clinical diagnostic criteria is satisfactory. We found similar results when we analysed the predictive value of these clinical diagnostic criteria. The positive predictive value of NINCDS 'probable DAT' category and that of the DAT diagnosis by DSM-III-R is very high (89-100%). This makes the use of these categories suitable for research purposes. However, the negative predictive value of both diagnoses is poor (33-63%), making these criteria unsuitable for diagnostic purposes in clinical practice.

The effects of additional pathology on the cognitive deficit in Alzheimer disease.

The diagnosis of Alzheimer disease (AD) according to current criteria is a combined clinical and pathological exercise. The clinical discrimination of AD from other types of dementia may be complicated when the patient suffers from more than one disease. In particular the concomitant presence of other neurological conditions may significantly influence the severity of cognitive deficit. In this study we analyze the extent of the influence of vascular and other neurodegenerative pathology on the cognitive deficit in a consecutive series of 88 prospectively assessed elderly subjects. We find that, for any given level of cognitive deficit, the densities of either all plaques or neuritic plaques alone in the neocortex are significantly lower in cases of AD mixed with other CNS pathology than in cases of AD with no other CNS pathology. In AD combined with cerebrovascular disease, the total plaque density makes a significant contribution to cognitive deficit, while neurofibrillary tangle (NFT) densities do not. In contrast, in pure AD tangle density is the major determinant of cognitive deficit. Our findings draw attention to the influence of coexisting brain pathologies on the clinical manifestation of dementia in subjects with AD. These findings indicate that pathological diagnostic criteria for AD should take into account such additional pathology in demented subjects. They also improve understanding of the circumstances in which the amyloid component of AD can play a decisive role in precipitating clinical dementia.