Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy.

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the 'supply chain'. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient's airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization-based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients' prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

Intravenous Furosemide for Acute Decompensated Congestive Heart Failure: What Is the Evidence?

Use of intravenous furosemide rather than oral administration in acute decompensated congestive cardiac failure is universally recommended in international guidelines. We argue that this recommendation is not supported by the existing evidence, and suggest that trials should be performed to determine whether larger doses of oral furosemide should be prescribed prior to an IV switch. This could reduce length of hospital admissions and allow for more patients to be managed in the primary care setting.

Clinical assessment of carotid atherosclerosis inflammation by positron emission tomography.

Stroke caused by carotid atherosclerosis is a leading cause of mortality and the leading cause of disability in the developed world. For carotid plaques within the neurovascular territory of a recent stroke or transient ischaemic attack, surgical removal of the plaque (endarterectomy) has been clearly shown to reduce future cerebrovascular events. Management of asymptomatic plaques, however, is less clear because only a minority of these plaques will ultimately become symptomatic. Inflammation is a key feature which predicts whether a plaque is likely to rupture and hence lead to stroke. By identifying inflammation in vivo, positron emission tomography (PET) may be able to identify high risk plaques. This will allow clinicians to target intensive medical or surgical treatment to high risk patients.

Imaging of atherosclerosis.

It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features associated with a high-risk plaque, including a thin fibrous cap, large necrotic core, macrophage infiltration, neovascularization, and intraplaque hemorrhage, can now be probed by novel imaging techniques. Each technique has its own strengths and drawbacks. In this article, we review the various imaging modalities used for the evaluation and quantification of atherosclerosis.

The use of contrast enhanced ultrasound in carotid arterial disease.

Traditionally, stroke risk stratification has centred on the degree of internal carotid artery stenosis, and the presence of focal neurological symptoms. However, degree of stenosis alone is a relatively poor predictor of future stroke in asymptomatic patients; the Asymptomatic Carotid Surgery Trial highlighting the need to identify a subgroup of asymptomatics that may benefit from intervention. Attempting to define this subgroup has inspired imaging research to identify, in vivo, high-risk plaques. In addition to pre-operative risk stratification of carotid stenosis, contrast enhanced ultrasound (CEUS) may be employed in monitoring response to plaque-stabilising therapies. Unlike most contrast agents used for computed tomography and magnetic resonance imaging, microbubbles used in CEUS remain within the vascular space and can hence be used to study the vasculature. In addition to improving current carotid structural scans, CEUS has potential to add extra information on plaque characteristics. Furthermore, by targeting microbubbles to specific ligands expressed on vascular endothelium, CEUS may have the ability to probe plaque biology. This review describes the current carotid ultrasound examination and the need to improve it, rationale for imaging neovascularisation, use of CEUS to image neovascularisation, microbubbles in improving the structural imaging of plaque, potential problems with CEUS, and future directions.

Acetophenone as an anti-attractant for the western pine beetle, Dendroctonus Brevicomis LeConte (Coleoptera: Scolytidae).

Host location and colonization by bark beetles is dependent upon the relative and absolute amounts of attractant and antiattractant compounds available. Many investigations have lead to use of antiattractants for the management of these pests and have been especially focused on verbenone. However, recent studies have identified new antiattractants for several species of bark beetles. We report results of recent investigations of the response of western pine beetle, Dendroctonus brevicomis LeConte, to two recently identified antiattractants, acetophenone, and fenchyl alcohol, with verbenone as a standard of comparison, in northern California. Release of both acetophenone and verbenone resulted in significantly lower trap catches of D. brevicomis in aggregation pheromone-baited traps, while fenchyl alcohol was inactive. Acetophenone was the only antiattractant that did not reduce numbers of the most abundant predator of D. brevicomis, Temnochila chlorodia (Mannerheim), responding to the attractant pheromone of its prey. Aggregation pheromone-baited traps with acetophenone also had the highest predator/prey ratio. Our results suggest that acetophenone may be part of the intra- and interspecific interactions among sympatric species of bark beetles and may have application in their control.

Response to host volatiles by native and introduced populations of Dendroctonus valens (Coleoptera: Curculionidae, Scolytinae) in North America and China.

Bark beetles (Coleoptera: Curculionidae, Scolytinae) have specialized feeding habits, and commonly colonize only one or a few closely related host genera in their geographical ranges. The red turpentine beetle, Dendroctonus valens LeConte, has a broad geographic distribution in North America and exploits volatile cues from a wide variety of pines in selecting hosts. Semiochemicals have been investigated for D. valens in North America and in its introduced range in China, yielding apparent regional differences in response to various host volatiles. Testing volatiles as attractants for D. valens in its native and introduced ranges provides an opportunity to determine whether geographic separation promotes local adaptation to host compounds and to explore potential behavioral divergence in native and introduced regions. Furthermore, understanding the chemical ecology of host selection facilitates development of semiochemicals for monitoring and controlling bark beetles, especially during the process of expansion into new geographic ranges. We investigated the responses of D. valens to various monoterpenes across a wide range of sites across North America and one site in China, and used the resulting information to develop an optimal lure for monitoring populations of D. valens throughout its Holarctic range. Semiochemicals were selected based on previous work with D. valens: (R)-(+)-alpha-pinene, (S)-(-)-alpha-pinene, (S)-(-)-beta-pinene, (S)-(+)-3-carene, a commercially available lure [1:1:1 ratio of (R)-(+)-alpha-pinene:(S)-(-)-beta-pinene:(S)-(+)-3-carene], and a blank control. At the release rates used, (+)-3-carene was the most attractive monoterpene tested throughout the native range in North America and introduced range in China, confirming results from Chinese studies. In addition to reporting a more effective lure for D. valens, we present a straightforward statistical procedure for analysis of insect trap count data yielding cells with zero counts, an outcome that is common but makes the estimation of the variance with a Generalized Linear Model unreliable because of the variability/mean count dependency.

Spirocyclic restriction of nucleosides. An analysis of protecting group feasibility while accessing prototype anti-1-oxaspiro[4.4]nonanyl mimics.

[reaction: see text] The first spirocyclic nucleoside featuring a beta-hydroxyl (anti) at C5' has yielded to synthesis. While the OMOM functionality proved to be sensitive to the conditions necessary to incorporate heterocyclic bases, PMB protection of the carbinol was readily accommodated. The remarkably similar minimum-energy conformations of the title compounds relative to natural thymidine as deduced by Amber calculations in the gas phase are noted.

Cognitive abilities in left-handers: writing posture revisited.

Among 1848 young men appearing before the Danish draft board, 232 (13%) were left-handed. Of these, 118 (51%) used an inverted, or hook-like, writing posture, 49 (21%) used a non-inverted posture and the remaining 65 (28%) could not be categorized. There were no differences between left- and right-handers on a battery of four cognitive tests. However, inverted left-handers performed significantly or near-significantly better than the non-inverted left-handers on two of the four tests and significantly better on the total score for the test battery. These results support the contention that the inverted posture is adaptive for left-handers and suggest that it may be more likely to be adopted by those with better cognitive abilities. Our findings conflict with earlier reports from two decades ago, however, and the association may therefore be socially and culturally dependent.

1-Oxaspiro[4.4]nonan-6-ones. Synthetic access via oxonium ion technology, optical resolution, and conversion into enantiopure spirocyclic alpha,beta-butenolides.

A general approach to the synthesis of enantiomerically pure spirocyclic alpha,beta-butenolides is presented where the fundamental framework is rapidly elaborated by acid- or bromonium ion-induced rearrangement of the carbinol derived by addition of 2-lithio-4,5-dihydrofuran to cyclobutanone. Subsequent resolution of the resulting ketones by either sulfoximine or mandelate acetal technology has been applied effectively. The availability of these building blocks makes possible in turn the acquisition of the enantiomers of dihydrofurans typified by 17, 35, and 38 and lactones such as 25 and 31, as well as the targeted title compounds. Complementary reductions of the early intermediates provide the added advantage that the alpha- and beta-stereoisomeric carbinol series can be obtained on demand. These capabilities have been coordinated to allow the crafting of any member of the series in relatively few steps.

Adjusted and unadjusted energy usage rates both determine body fat and plasma leptin in male Fischer 344 rats.

Previous studies of the relationship between plasma leptin and energy usage have yielded contradictory findings. The present study was therefore conducted to clearly distinguish and measure the energy usage rate and the energy usage rate adjusted for a surrogate of metabolically active tissue mass. We investigated the simultaneous relationships between these two measures of energy usage, leptin, and body fat in 21-month-old adult male Fischer 344 rats on three different long-term dietary regimens: (1) continuous ad libitum feeding (Ad-lib); (2) ad libitum feeding until early adulthood, and then continuous 60% caloric restriction (CR); and (3) ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, and then ad libitum feeding for 5 months (CR/Ad-lib). Two versions of the daily usage rate were measured: daily dietary caloric intake (DCI), and daily energy expenditure (EE) based on indirect calorimetry. Two versions of the metabolically active tissue mass were also measured: fat-free mass (FFM), and the sum of the weight of the heart, brain, liver, and kidneys. Energy usage rates were adjusted for these measures of metabolically active tissue mass to yield measures of the energy metabolic rate. Correlation, regression, and path analyses showed that both the energy usage rate and adjusted energy usage rate played important independent roles in determining body fat and plasma leptin, but only after multivariate techniques were used to account for the simultaneous interactions between variables. Increases in the energy usage rate were associated with increases in body fat and the adjusted energy usage rate. Increases in the adjusted energy usage rate were associated with decreases in body fat and plasma leptin. These findings suggest that differences in subjects adjusted energy usage rate could explain some of the apparently contradictory findings concerning the relationship between energy usage and plasma leptin in previously published studies. In conclusion, this appears to be the first study to clearly separate and quantify the effects of the energy usage rate and adjusted energy usage rate on body fat and plasma leptin. The findings suggest that under conditions of long-term stable body weight, both of these measures of energy usage play independent simultaneous roles in determining body fat and plasma leptin.

Relation of low and moderate intensity exercise with acute mood change in college joggers.

This study investigated a possible relationship between exercise intensity and mood alteration that commonly is associated with physical activity. 91 college students completed the Profile of Mood States before and after 20 min. of jogging at three intensities: 55%, 75%, and 79% of age-adjusted maximum heart rate on different occasions. Exercisers also completed a demographic inventory, a Lie Scale, and the State-Trait Anxiety Inventory. Contrary to our expectations, the interaction between exercise intensity and pre-post mood benefits was not significant. Supporting the manipulation of exercise intensity, the univariate interaction between exercise intensity and pre-post exercise scores on Fatigue was significant. Joggers reported short-term mood benefits on the combined subscales of the Profile of Mood States, and each subscale contributed to the benefits. Thus, regardless of the low- or moderate-intensity, participants reported that they "felt better" after exercising.

Dot Enumeration Perceptual Organization Task (DEPOT): evidence for a short-term visual memory deficit in schizophrenia.

The Dot Enumeration Perceptual Organization Task (DEPOT) evaluates the validity of 2 specific competing cognitive models of early input dysfunction in schizophrenic individuals: a primary Stage 1, sensory store, perceptual organization deficit vs. a Stage 2, short-term visual memory (STVM) deficit. DEPOT was also designed to assess the hypothesis that schizophrenic individuals tend to perform poorly on all cognitive tasks. In DEPOT both number and form judgments are made about the same dot patterns. A response delay manipulation assesses the persistence and operation of STVM. The study included 41 psychotic inpatients (8 with acute and 16 with chronic schizophrenia and 7 with bipolar and 10 with nonbipolar affective disorder) and 38 controls (22 college students and 16 hospital personnel). Although the pattern of results was consistent with neither the Stage 1 deficit nor the general deficit hypotheses, a Stage 2, STVM deficit hypothesis could account parsimoniously for the data.

Thirty-year secular trends in the cognitive abilities of Danish male school-leavers at a high educational level.

A nationally representative sample of Danish males finishing school in 1989, or shortly before, with a studentereksamen (the highest qualification in the Danish school system) was found to score generally lower on a battery of four cognitive tests than a comparable sample of Danish males who had taken the same tests shortly after finishing school in the late 1950s or early 1960s. This decline appears attributable to the increasing proportions of students who obtain the studentereksamen and is quite compatible with an overall increase in test scores, also found in our data, for the general population over the same time period. For those who obtain the studentereksamen, the decline has been most marked in a test of verbal analogies. It has been smaller for tests of logical and spatial reasoning, and scores on a test of numerical ability have actually improved over the 30 years. This differential pattern may be the result of both student changes and curricular changes within Danish schools.

Mood alteration with yoga and swimming: aerobic exercise may not be necessary.

The mood benefits of Hatha yoga and swimming, two activities that differ greatly in aerobic training benefits, were examined. College students (N = 87) in two swimming classes, a yoga class, and a lecture-control class completed mood and personality inventories before and after class on three occasions. A multivariate analysis of variance indicated that both yoga participants (n = 22) and swimmers (n = 37) reported greater decreases in scores on Anget, Confusion, Tension, and Depression than did the control students (n = 28). The consistent mood benefits of yoga supported our earlier observation that the exercise need not be aerobic to be associated with mood enhancement. However, underlying and causal mechanisms remain uncertain. Among the men, the acute decreases in Tension, Fatigue, and Anger after yoga were significantly greater than those after swimming. Yoga may be even more beneficial than swimming for men who personally select to participate. The women reported fairly similar mood benefits after swimming and yoga. It seems that aerobic exercise may not be necessary to facilitate the mood benefits. Also, students with greater mood changes attended class more regularly than those who reported fewer psychological benefits. Maximizing the immediate psychological benefits of exercise might be one way to encourage adults to be physically active.

Intelligence and educational level in adult males at the extremes of stature.

Stature and intellectual ability are commonly found to correlate positively (r approximately 0.2). In this study we have assessed whether this relationship holds true at the extremes of stature in adults. From a representative study population of 76,111 young Danish men, we defined an extremely short group as those below the 2d percentile (less than or equal to 163 cm) and an extremely tall group as those above the 98th percentile (greater than or equal to 191 cm). The short group had intelligence test scores and educational levels lying at approximately two-thirds of a standard deviation below the overall means. The tall group had means lying approximately one-half standard deviation above the overall means. These deviations are to a large degree in agreement with the observed overall correlations of height with intelligence test scores (r = 0.244) and with educational level (r = 0.264). Both groups, however, appear to score somewhat below the levels expected from a purely linear relationship. For the short group there appear to be local factors that are particularly detrimental to intellectual ability. For the tall group corresponding local factors are relatively independent of intellectual ability.