Metabolic constraints on the body size scaling of extreme population densities.

Pest outbreaks, harmful algal blooms and population collapses are extreme events with critical consequences for ecosystems. Therefore, understanding the ecological mechanisms underlying these extreme events is crucial. We evaluated theoretical predictions on the size scaling and variance of extreme population abundance by combining (i) the generalized extreme value (GEV) theory and (ii) the resource-limited metabolic restriction hypothesis for population abundance. Using the phytoplankton data from the L4 station in the English Channel, we showed a negative size scaling of the expected value of maximal density, whose confidence interval included the predicted metabolic scaling (α = -1) supporting theoretical predictions. The role of resources and temperature in the distribution of the size-abundance pattern and residuals was well characterized by the GEV distribution. This comprehensive modelling framework will allow to elucidate community structure and fluctuations and provide unbiased return times estimates, thereby improving the prediction accuracy of the timing of the population outbreaks.

Low-cost treatment method for organic matter and nutrients in landfill leachate.

In this study, the ability of low-cost composite adsorbents to treat organic compounds in terms of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) was investigated. The composite adsorbents were composed of washed sea sand (WSS), dewatered alum sludge (DAS), zero-valent iron (ZVI), and granular activated carbon (GAC). The removal efficiency of COD in landfill leachate by a composite adsorbent (composed of WSS (40%), DAS (40%), ZVI (10%), and GAC (10%) in weight) was 79.93 ± 1.95%. The corresponding adsorption capacity was 8.5 mg/g. During batch sorption experiments, the maximum COD removal efficiencies given by DAS, WSS, ZVI, and GAC were 16, 51.3, 42, and 100.0%, respectively. The maximum removal efficiencies of the above composite adsorbent for TN and TP were 84.9 and 97.4%, respectively, and the adsorption capacities were 1.85 and 0.55 mg/g, respectively. The Elovich isotherm model gave the best fit for COD, TN, and TP adsorption. This composite adsorbent can treat more than one contaminant simultaneously. The application of DAS and ZVI to make an efficient adsorbent for wastewater treatment would be a good re-use application for them, which would otherwise be landfilled directly after their generation.

Influence on the saturable absorption of the induced losses by photodeposition of zinc nanoparticles in an optical fiber.

In this work, the influence of induced losses on the saturable absorption by zinc nanoparticles photodeposited onto the core of an optical fiber end is reported. Samples with different losses were obtained by the photodeposition technique using a continuous wave laser at 1550 nm. The nonlinear absorption of the saturable absorber was characterized by the P-scan technique using a high-gain pulsed erbium-doped fiber amplifier. The results have demonstrated that for optical fibers with variable induced losses by deposited nanoparticles, the modulation depth increases proportionally based on the nonlinear absorption coefficient. With induced losses fixed at 3 dB, it was demonstrated that the modulation depth increased as a function of the optical power used in the photodeposition process. The saturation intensity of the saturable absorber presents small shifts for higher intensities.

Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK.

The with no lysine (K) (WNK) family of enzymes is best known for control of blood pressure through regulation of the function and membrane localization of ion cotransporters. In mice, global as well as endothelial-specific WNK1 gene disruption results in embryonic lethality due to angiogenic and cardiovascular defects. WNK1(-/-) embryos can be rescued by endothelial-specific expression of a constitutively active form of the WNK1 substrate protein kinase OSR1 (oxidative stress responsive 1). Using human umbilical vein endothelial cells (HUVECs), we explored mechanisms underlying the requirement of WNK1-OSR1 signaling for vascular development. WNK1 is required for cord formation in HUVECs, but the actions of the two major WNK1 effectors, OSR1 and its close relative SPAK (STE20/SPS1-related proline-, alanine-rich kinase), are distinct. SPAK is important for endothelial cell proliferation, whereas OSR1 is required for HUVEC chemotaxis and invasion. We also identified the zinc-finger transcription factor Slug in WNK1-mediated control of endothelial functions. Our study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells and an unanticipated link between WNK1 and Slug that is important for angiogenesis.

Constructing a framework for quality activity in primary care.

INTRODUCTION: In 2009, the Royal New Zealand College of General Practitioners commissioned the development of a framework to facilitate quality-improvement activity in primary care settings. This paper outlines the development of the framework, which integrates concepts of quality with the reality of practice-based clinical care, and discusses its value for primary care quality improvement. METHOD: Framework development involved: (1) literature review of theoretical approaches to healthcare quality; (2) field work utilising a mixed methods approach to obtain empirical data; and (3) model design. RESULTS: Primary care practitioners are juggling competing priorities. Models and tools that promote quality-related activity at practice level need to take into account, and incorporate by design, day-to-day clinical and practice functions. CONCLUSIONS: The quality framework identifies the components of primary care practice and locates this model within the concepts and activities necessary for quality improvement. It may be used by primary care organisations and practices to facilitate focussed quality-improvement activity and self-directed process review. The framework was developed for, and within a New Zealand primary care setting, and is applicable internationally and within other healthcare settings.

Development and Validation of a Holistically Based Follow-Up Pain Assessment Diary Leading to Holistic Nursing for Patients with Cancer Pain in Sri Lanka.

Purpose of the study: The study aimed to develop and validate a holistically based follow-up pain assessment diary for patients with cancer pain in Sri Lanka. Design of the study: Mixed-method design adapted. Methods used: Developing a pain diary and testing its psychometric qualities were done in two phases. Comprehensive literature research and qualitative semistructured interviews with patients, clinical, and subject specialists created the pain diary items. Content, face, construct, criterion validity, and reliability were evaluated. Findings: The essential domains to be assessed were identified under six main categories; pain and related characteristics, physical, psychological, social, spiritual, and financial aspects. The average variance extracted from the subscales "Influence on daily life," "Gastric disturbances," and "Pain intensity" were 0.526, 0.562, and 0.696, respectively. The heterotrait-monotrait criterion values between subscales were from 0.691 to 0.44, which was lower than the threshold. Good to excellent correlation coefficients were demonstrated with the scores of reference tools. Cronbach's alpha was computed for each subscale and ranged from 0.75 to 0.92 and composite reliability from 0.921 to 0.826. Conclusions: Pain diary is a reliable and valid instrument for follow-up assessment of holistic pain experience enabling holistic nursing among patients with cancer pain in Sri Lanka.

Aggressive strategies of the COVID-19 pandemic on the apparel industry of Sri Lanka using structural equation modeling.

During the COVID-19 crisis, the apparel industry faced many challenges. Aggressive cost-cutting strategies became a top priority, and in turn, these influenced stressors and adversely affected business sustainability. This study examines the impact of aggressive strategies during the COVID-19 pandemic on business sustainability in the apparel industry of Sri Lanka. Further, it investigates whether the relationship between aggressive cost-cutting strategies and business sustainability was mediated by employee stress, considering aggressive cost reduction strategies and workplace environmental changes. This was a cross-sectional study with data collected from 384 employees in the apparel industry in Sri Lanka. Structural Equation Modelling (SEM) was applied to analyze the direct and indirect effects of aggressive cost reduction strategies and workplace environmental changes on sustainability with mediating effects of stress. Aggressive cost reduction strategies (Beta = 1.317, p = 0.000) and environmental changes (Beta = 0.251, p = 0.000) led to an increase in employee stress but did not affect business sustainability. Thus, employee stress (Beta = -0.028, p = 0.594) was not a mediator in the relationship between aggressive cost-cutting strategies and business sustainability; business sustainability was not a dependent variable. The findings proved that managing workplace stress, particularly improving stressful working environments and aggressive cost reduction strategies, can enhance employee satisfaction. Thus, managing employee stress could be beneficial for policymakers to focus on the area(s) required to retain competent employees. Moreover, aggressive strategies are unsuitable to apply during crisis to enhance business sustainability. The findings provide additional knowledge to the existing literature, enabling employees and employers to predict causes of stress and serve as a significant knowledge base for further studies.

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat.

AIM/HYPOTHESIS: We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy. METHODS: Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg(-1) day(-1), pump), or diabetic + lisinopril (10 mg kg(-1) day(-1), drinking water) rats were evaluated over 16 weeks. For oxygen-induced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg(-1) day(-1), pump) or lisinopril (10 mg kg(-1) day(-1), drinking water) was administered during retinopathy development between postnatal days 12 and 18. RESULTS: Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg(-1) day(-1) aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg(-1) day(-1) aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg(-1) day(-1) aliskiren and normalised by 30 mg kg(-1) day(-1) aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels. CONCLUSIONS/INTERPRETATION: Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.

Regression of melanoma metastases following treatment with the n-bisphosphonate zoledronate and localised radiotherapy.

We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.

Hospital blood inventory practice: the factors affecting stock level and wastage.

To analyse the Issuable Stock Index (days worth of stock) and wastage in relation to data continuously collected by the Blood Stocks Management Scheme (BSMS) with aspects of blood inventory management practice determined by the 2006 hospital inventory practice survey (IPS). The BSMS collects blood inventory data from hospitals and blood services in England, Wales and Northern Ireland. Data sets were constructed from information obtained from the 2006 IPS, which included questions on the crossmatch reservation period, methods for calculating the blood order and stock share relationships between hospitals. Two of the Scheme's measures that can indicate a hospital's blood inventory management performance were used to present blood stock and wastage data in a comparable format. Data were analysed using the Student's t-test. The results showed significantly lower inventory and wastage in hospitals which used a 24-h reservation period compared with 48 h (P = 0.02 and P = 0.04, respectively), and for hospitals that used their computer for calculating the blood order compared with those that used a 'visual review' (P = 0.02 and P < or = 0.001, respectively). A strong correlation co-efficient (0.61) was found for a relationship between a hospital's stock level and wastage. The study showed that differences in stock management practice between hospitals are associated with significant differences in stock levels and wastage of blood. The paper identifies examples of best practice.

Paid employment and common mental disorders in 50-64-year olds: analysis of three cross-sectional nationally representative survey samples in 1993, 2000 and 2007.

AIMS: Associations between employment status and mental health are well recognised, but evidence is sparse on the relationship between paid employment and mental health in the years running up to statutory retirement ages using robust mental health measures. In addition, there has been no investigation into the stability over time in this relationship: an important consideration if survey findings are used to inform future policy. The aim of this study is to investigate the association between employment status and common mental disorder (CMD) in 50-64-year old residents in England and its stability over time, taking advantage of three national mental health surveys carried out over a 14-year period. METHODS: Data were analysed from the British National Surveys of Psychiatric Morbidity of 1993, 2000 and 2007. Paid employment status was the primary exposure of interest and CMD the primary outcome - both ascertained identically in all three surveys (CMD from the revised Clinical Interview Schedule). Multivariable logistic regression models were used. RESULTS: The prevalence of CMD was higher in people not in paid employment across all survey years; however, this association was only present for non-employment related to poor health as an outcome and was not apparent in those citing other reasons for non-employment. Odds ratios for the association between non-employment due to ill health and CMD were 3.05 in 1993, 3.56 in 2000, and 2.80 in 2007, after adjustment for age, gender, marital status, education, social class, housing tenure, financial difficulties, smoking status, recent physical health consultation and activities of daily living impairment. CONCLUSIONS: The prevalence of CMD was higher in people not in paid employment for health reasons, but was not associated with non-employment for other reasons. Associations had been relatively stable in strength from 1993 to 2007 in those three cross-sectional nationally representative samples.

Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice.

We have developed a variant of functional magnetic resonance imaging (fMRI) designed to be sensitive to static neuronal function. This method is based on resting instead of dynamic changes in oxygen-dependent signal and therefore allows for a spatial resolution that can detect signal from different hippocampal subregions in human subjects as well as in mice. We found that hippocampal signal was significantly diminished in elderly subjects with memory decline compared to age-matched controls, and different subjects showed dysfunction in different subregions. Among healthy elders, signal intensity from the subiculum was correlated selectively with memory performance. This method does not require an activation task; it can be used in anesthetized normal and in genetically modified and cognitively impaired mice. In mice the signal was found to be sufficiently sensitive to detect functional changes in the absence of underlying anatomical changes.

Circuit mechanisms underlying memory encoding and retrieval in the long axis of the hippocampal formation.

Circuits within the hippocampal formation are active during memory processing. Here we used functional magnetic resonance imaging (fMRI) to examine multiple sites across the long axis of the hippocampal formation while subjects performed different phases of an associative memory task, learning to associate faces with names. Viewing faces and hearing names in isolation resulted in separate hippocampal activation patterns. Pairing faces with names resulted a spatially redistributed activation pattern, rather than a simple summation of the activation patterns resulting from viewing faces and hearing names in isolation. Recalling names when cued with faces reactivated a pattern similar to that found during paired training. Finally, the activation patterns representing faces and names were found to be experience dependent, emerging with repeated exposure. Interpreted in the context of hippocampal anatomy and physiology, these findings reveal hippocampal circuit mechanisms that underlie memory encoding and retrieval.

Reproductive activity of Pelibuey and Suffolk ewes at 19 degrees north latitude.

Under photoperiod regulated conditions, some Pelibuey ewes appear to express estrous cycles continuously throughout the year. Ovulatory activity of Suffolk ewes has not being determined at 19 degrees N. The aim of the present study was to describe the annual reproductive cycle of Pelibuey and Suffolk ewes under natural conditions at 19 degrees N. Ten adult ewes of each breed were maintained under natural environmental conditions, on a constant plane of nutrition and isolated from rams. The ovulatory activity of both breeds was monitored over 2 years (2003 and 2004) by quantifying progesterone concentrations in blood samples taken twice a week. For both breeds, the proportion of ovulating ewes per month and year was analyzed by chi(2). The duration of anestrus was compared between breeds and years by analysis of variance. Correlation of ambient temperature and weight changes with the ovulatory activity was evaluated by regression procedure. Ovulatory activity was different (P<0.05) between breeds from February to July. Pelibuey sheep (60%, 6 of 10) ovulated continuously during the entire study; one animal was eliminated in the second year, due to ovarian follicular cysts and three ewes had anestrous periods from 65+/-46 to 70+/-36 days. Suffolk ewes displayed reproductive seasonality similar to that observed in sheep of the same breed in latitudes greater than 35 degrees . Within breed, reproductive behavior of sheep was similar between years, with the only difference (P<0.05) observed in February for Pelibuey and in July for Suffolk relative to other months. Ambient temperature was not correlated with ovulatory activity. The body weight of Pelibuey ewes was constant during the entire study and was not correlated with ovulatory activity. There was, however, an increase on the body weight of Suffolk ewes, but this variation was not related to ovulatory activity. These findings lead to the conclusion that at 19 degrees N, a high proportion of Pelibuey ewes is capable of ovulating throughout the year, whereas Suffolk ewes undergo seasonal anestrous periods similar to those observed in individuals of the same breed at latitudes greater than 35 degrees . Identification of continuous ovulatory Pelibuey ewes may be the first step for developing a selection program against seasonality to increase lambing frequency.

Anti-tuberculosis drug inducd hepatitis - a Sri Lankan experience.

OBJECTIVE: To assess the incidence of anti-tuberculosis (TB) drug induced hepatitis (AIH) in Sri Lankan patients, determine risk factors of AIH, and to address management options in AIH. DESIGN: A prospective study. SETTING: Chest Hospital, Welisara, Sri Lanka, from April 2001 to April 2002. PATIENTS: Seven hundred and eighty three patients with a confirmed diagnosis of TB and resident in the Colombo and Gampaha districts who presented to Chest Hospital, Welisara, Sri Lanka. METHODS: WHO recommended treatment was commenced in all cases. AIH was diagnosed when patients complained of decreased appetite with nausea or vomiting and elevated serum bilirubin (SB; >1.1 mg/dL) or elevated serum alanine transferase (ALT; > 3 times upper limit of normal). RESULTS: Of 783 enrolled patients, 74 (9.5%) developed AIH, the majority (58%) developing AIH within the first 2 weeks of the intensive phase of treatment. AIH was more common among patients over 60 years (p = 0.018), who developed pulmonary TB (p = 0.028), and in patients weighing 33-55 kg (p = 0.004). Age, weight and rifampicin overdosage were significant predictors of AIH. Of the 74 AIH patients, standard treatment was restarted in 60, treatment modified in six, two defaulted and six died. CONCLUSIONS: The incidence of AIH in Sri Lanka is 9.5% in treated patients. AIH was associated with age, low body weight and rifampicin overdosage.

Inhibitor treatment of peripheral mononuclear cells from Parkinson's disease patients further validates LRRK2 dephosphorylation as a pharmacodynamic biomarker.

Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with increased risk of Parkinson's disease (PD). Thus, LRRK2 kinase inhibitors are in development as potential Parkinson's disease therapeutics. A reduction in the constitutive levels of phosphorylation on leucine-rich repeat kinase 2 (LRRK2) is currently used to measure target engagement of LRRK2 kinase inhibitors in cell and animal models. We aimed to determine if reduced phosphorylation of LRRK2 following inhibitor treatment is also a valid measure of target engagement in peripheral mononuclear cells from Parkinson's disease patients. Peripheral mononuclear cells from idiopathic Parkinson's disease patients and controls were treated ex vivo with two structurally distinct inhibitors of LRRK2, at four different doses, and immunoblotting was used to assess the reduction in LRRK2 phosphorylation at Ser910, Ser935, Ser955 and Ser973. Both inhibitors showed no acute toxicity in primary cells and both inhibitors reduced the constitutive phosphorylation of LRRK2 at all measured residues equally in both control and Parkinson's disease groups. Measuring the reduction in LRRK2 phosphorylation resulting from LRRK2 kinase inhibition, is thus a valid measure of acute peripheral target engagement in Parkinson's disease patients. This is important if LRRK2 kinase inhibitors are to be used in a clinical setting.

Acute kidney injury following ingestion of plate developer (sodium metasilicate): a case report.

BACKGROUND: Plate developer is a chemical used in the printing industry and is a corrosive alkaline agent containing sodium metasilicate as the main substance. Plate developer poisoning is rare. Literature search revealed only a single case report of fatal sodium metasilicate poisoning (Z Rechtsmed 94(3):245-250, 1985). There are no reports of acute kidney injury related to ingestion of sodium metasilicate containing substances. CASE REPORT: A 52-year-old Sri Lankan male with a history of hypertension and affective disorder presented following ingestion of about 150 ml of plate developer solution. He developed severe upper airway obstruction due to laryngeal edema and underwent tracheostomy. While in the ward he developed features of acute kidney injury with high serum creatinine levels and persistent hyperkalemia which necessitated temporary haemodialysis. Because of the corrosive effect, he developed severe inflammation of the upper gastro intestinal tract with narrowing of esophagus and pyloric region, requiring feeding jejunostomy. He died while waiting for the surgery for pyloric stenosis. CONCLUSIONS: Acute kidney injury is a potential treatable complication of plate developer poisoning other than its complications related to corrosive effects. Regular monitoring of renal functions in such a patient would be useful for early recognition of acute kidney injury.

Evaluation of dose delivery accuracy of Gamma Knife by polymer gel dosimetry.

The BANG polymer gel dosimeter was used to evaluate 3D absorbed dose distributions in tissue delivered with Gamma Knife stereotactic radiosurgery systems. We compared dose distributions calculated with Leksell GammaPlan (LGP) treatment-planning software with dose distributions measured with the polymer gel dosimeter for single-shot irradiations. Head-sized spherical glass vessels filled with the polymer gel were irradiated with Gamma Knife. The phantoms were scanned with a 1.0T MRI scanner. The Hahn spin-echo sequence with two echoes was used for the MRI scans. Calibration relations between the spin-spin relaxation rate and the absorbed dose were obtained by using small cylindrical vials, which were filled with the polymer gel from the same batch as for the spherical phantom. We made voxel-by-voxel comparisons of measured and calculated dose distributions for 31 x 31 x 31 dose matrix elements. With the 3D dose data we calculated the tumor control probability (TCP) and normal tissue complication probability (NTCP) for a simple model. For the maximum dose of 100 Gy, the mean and one standard deviation of differences between the measured and the calculated doses were the following: -0.38+/-4.63 Gy, 1.49+/-2.77 Gy, and -1.03+/-4.18 Gy for 8-mm, 14-mm, and 18-mm collimators, respectively. Tumor control probability values for measurements were smaller than the calculations by 0% to 7%, whereas NTCP values were larger by 7% to 24% for four of six experiments.

Neuroendocrine regulation of adrenal 5'-monodeiodination during acute cold exposure in the rat. I. Effects of hypophysectomy.

Circulating levels of T4, T3, corticosterone, noradrenaline, and adrenaline, as well as 5'-monodeiodinase activity (5'-MA) were measured in control and hypophysectomized rats acutely exposed to cold environment (15-120 min, 4 C). In addition to the well known activation of the sympathoadrenomedullary system and the hypothalamic-pituitary-adrenal and-thyroid axes, cold exposure was followed by a rapid and sustained increase of 5'-MA in the hypothalamus, and a byphasic course of activation in the adrenal gland in control rats. The adrenal rapid activation (30 min) corresponded to the medulla and the slower activation (120 min) to the cortex. Both, the basal adrenal 5'-MA and the response to cold in adrenal and hypothalamus were 2-fold higher in hypophysectomized rats compared to control. The time course of enzyme activation in these structures suggests that: 1) organ-specific increases in 5'-MA may be associated to a simultaneous rise in their metabolic and/or functional activity, 2) the triggering mechanisms involves an immediate sympathetic signal activating the hypothalamic-adrenal medulla response and a pituitary signal eliciting a slower adrenocortical response, and 3) the compensatory sympathetic hyperactivity after panhypopituitarism contribute to enhance both the adrenal enzyme basal activity and the hypothalamic and adrenal hyperresponse to cold stress.

Interhemispheric transfer of language in patients with left frontal cerebral arteriovenous malformation.

Cerebral arteriovenous malformations (AVMs) are frequently evaluated before therapeutic embolization by superselective injection of anesthetics into individual arterial branches so as to determine whether permanent occlusion would affect eloquent function. In Experiment 1, we used this adaptation of the Wada procedure to study three right-handed adult patients with left frontal cerebral AVMs by injecting vessels in Wernicke's and Broca's areas, respectively, and assessing language functions. The results showed that superselective testing in the inferior division of the left MCA in all three patients produced a dense Wernicke's aphasia. Injections into the left frontal regions, however, resulted in right paresis in all patients, but no language deficits including no loss of fluency. In Experiment 2, Patient 2 underwent fMRI activation for spontaneous word-list generation using multi-slice echo planar BOLD techniques at 1.5 Tesla. A voxel-by-voxel comparison of rest vs activation for each task was performed with a Z-score threshold of 2.5 SD for activated voxels. There was activation in the right hemisphere in the insula, frontal operculum pars opercularis, and inferior frontal gyrus, an area homologous to Broca's area in the left hemisphere. There was also activation in the left hemisphere in the Rolandic region, but language function was unaffected during Wada testing in this area. These data suggested that features of expressive language were no longer controlled by the left frontal lobe where the AVM was located, and provided new evidence for interhemispheric re-organization under conditions of chronic neurovascular disease.