“Background: Negative affect is an important predictor of


“Background: Negative affect is an important predictor of smoking behavior, and many smokers believe

that smoking reduces negative affect. However, it is unclear whether such beliefs, known as negative reinforcement smoking outcome expectancies (NRSOE), are associated with changes in negative affect in response to nicotine deprivation and administration.\n\nMethods: Smokers (N = 114) participated in 4 sessions that balanced overnight smoking deprivation (12-h deprived vs. ad lib) and nasal spray administration (nicotine vs. placebo). Corrugator supercilii (CUR) EMG, skin conductance (SCR), and in-session ratings were collected while the participants viewed affective, cigarette-related, and neutral slides. Retrospective questionnaire data were collected prior to slide viewing. NRSOE were

GSK3326595 cost determined using the Smoking Consequences Questionnaire – Adult Nicotine Affect Reduction scale (SCQ-NAR).\n\nResults: High scores on the SCQ-NAR were associated PXD101 datasheet with smaller COR EMG to unpleasant slides following nicotine nasal spray administration compared to placebo spray, regardless of overnight deprivation. Smokers who had high scores on the SCQ-NAR had smaller SCR, following nicotine nasal spray administration compared to placebo spray, but only after overnight deprivation. The in-session ratings and retrospective questionnaire measures indicated that

smokers who had high scores on the SCQ-NAR experienced greater negative affect and craving, and less positive affect, than smokers with low scores on the SCQ-NAR, regardless of nicotine exposure.\n\nConclusions: Our questionnaire results suggest that while smokers who have high NRSOE self-report greater overall levels of negative affect and craving, while the psychophysiological data suggest that such smokers may experience negative affect reduction when blindly administered a dose of nicotine. (C) BLZ945 mouse 2011 Elsevier Ireland Ltd. All rights reserved.”
“Plasma exchange is a therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. To apply this treatment to patients appropriately, it is essential to understand the methods to remove plasma, its effects on normal plasma constituents, the role of replacement fluids in the treatment, and the risks associated with the procedure. To facilitate the appropriate evidence-based use of plasma exchange and to encourage research, the American Society for Apheresis has published guidelines providing practical guidance and information to those responsible for ordering or providing this treatment.”
“Objective: To assess the effectiveness of substance abuse interventions for their ability to reduce adolescent alcohol use.

The goal of this study is to identify which patient and tumor cha

The goal of this study is to identify which patient and tumor characteristics are associated with specific preoperative symptoms; surgical complications, patient outcomes, and tumor recurrence in order to guide craniopharyngioma treatment. We retrospectively identified 84 patients with newly diagnosed craniopharyngiomas treated at our institution from

1986-2010. We used binary logistic regression and survival analysis to determine the effect of several variables (including sex, age, tumor size, location, surgical approach, and extent of resection) on preoperative symptoms and postoperative outcomes, including complication rates and tumor check details recurrence. Age and tumor location were associated with increased rates of preoperative symptoms, with children being more likely than adults to present with endocrine dysfunction, and intraventricular tumors being more likely than extraventricular tumors to present with headaches and hydrocephalus. A transcranial surgical approach was associated with 1.5 times higher rate of surgical complications

than transsphenoidal selleck products surgery, while only intraventricular tumor location was associated with a poorer patient outcome. The main factor significantly associated Galunisertib in vitro with tumor recurrence was extent of resection. We conclude that intraventricular tumor location is most highly correlated with preoperative symptoms. If feasible, transsphenoidal approaches are preferred, as they result in fewer surgical complications, and gross total resections are optimal because they lead to lower

rates of recurrence. When gross total resection is not possible, we favor multimodal treatment approaches. (C) 2014 Elsevier Ltd. All rights reserved.”
“Accumulating evidence strongly supports the premise that testosterone may be a key player in fetal programming on hypertension. Studies have shown that gestational protein restriction doubles the plasma testosterone levels in pregnant rats. In this study, we hypothesized that elevated testosterone levels in response to gestational protein restriction were caused by enhanced expression of steroidogenic enzymes or impaired expression of Hsd17b2, a known testosterone inactivator that converts testosterone to androstenedione in placenta. Pregnant Sprague-Dawley rats were fed normal (20% protein, control; n = 10) or a low-protein diet (6% protein, PR; n = 10) from Day 1 of pregnancy until killed at Days 14, 18, or 21.

The goal was to determine whether a regularly flooded area connec

The goal was to determine whether a regularly flooded area connected to a

freshwater tidal river could act as an important foraging area for European eel, and if so, to what extent the diet of eels in this flooding area differed from that of eels foraging in the river itself. The stomach contents of eels from the River Schelde were compared with eels from the Lippenbroek, an adjacent CRT area. Prey diversity (H’) of individual eels was about four times higher in the Lippenbroek than in the River Schelde. Moreover, 12 prey categories in eel stomachs from the Lippenbroek were found whereas only three categories were retrieved from eels in the River Schelde. In the Z-VAD-FMK clinical trial Lippenbroek, eels fed on terrestrial organisms (lumbricids, caterpillars and other insects), but also on fish and fish eggs and to a lesser extent on other Selleckchem Cyclosporin A aquatic prey (Lumbricullidae,

chironomids and Hirudinea). In contrast, eels from the main river fed mainly on tubificids, fish, and some gammarids. Consequently, eels in the Schelde estuary are opportunistic feeders, but with a preference for large benthic prey. The number and weight of aquatic organisms ingested by eels in the Lippenbroek is not significantly different from the River Schelde. However, eels foraging in the Lippenbroek area had consumed significantly more terrestrial prey. Furthermore the total caloric value estimated for the ingested prey of eels from the Lippenbroek (derived from the literature) IPI-145 chemical structure was about twice as high as that for eels from the River Schelde. While the condition index remained inconclusive, an Ancova revealed that eels captured in the Lippenbroek were significantly heavier for a given length than eels captured in the Schelde. The study showed that with a controlled reduced tide to restore lateral connectivity of large tidal rivers with their adjacent floodplains, high quality habitats for the European eel are

created. These measures could significantly contribute to the production of eels in better condition, which have better chances to reproduce successfully. Hence, wetland restoration could enhance the recovery of the European eel stocks.”
“Five new organotin(IV) complexes of 2-hydroxyacetophenone-2-methylphenylthiosemicarbazone [H(2)dampt, (1)] with formula [RSnCln-1(dampt)] (where R = Me, n = 2 (2); R = Bu, n = 2 (3); R = Ph, n = 2 (4); R = Me-2, n = 1 (5); R = Ph-2, n = 1 (6)) have been synthesized by direct reaction of H(2)dampt (1) with organotin(IV) chloride(s) in absolute methanol. The ligand (1) and its organotin(IV) complexes (2-6) were characterized by CHN analyses, molar conductivity, UV-Vis, FT-IR, H-1, C-13, and Sn-119 NMR spectral studies. H(2)dampt (1) is newly synthesized and has been structurally characterized by X-ray crystallography.

Ultrasound agreed with panorex x-rays in 6 (86%) of 7 cases One

Ultrasound agreed with panorex x-rays in 6 (86%) of 7 cases. One case where US disagreed with x-rays was evaluated by dentistry consultants; and incision and drainage were performed, confirming the presence of an abscess. An x-ray diagnosis of periapical abscess was made in 12 (63%) of 19 Prexasertib mouse patients. Ultrasound agreed with panorex x-ray in 10 (83%) of 12 cases. In 1 of the 2 cases where US disagreed with panorex x-rays, x-ray abnormalities were reported on the nonsymptomatic side. The other

patient was given antibiotics and recommended outpatient follow-up. Follow-up information was not available to further confirm the presence of an abscess. Assuming that the patient who was lost to follow-up had dental abscess, the sensitivity and specificity of US in diagnosing a dental abscess were 92% and 100%, respectively.\n\nConclusions: Bedside US is nonionizing, is readily available, and can provide an alternative to panorex x-rays in the evaluation of a dental abscess in ED. (C) 2011 Elsevier Inc. All rights reserved.”
“Noninvasive imaging of the coronary arteries using multicletector CT (MDCT) represents one of the most promising diagnostic imaging advances in contemporary cardiology. selleck inhibitor This challenging application has driven

a rapid and impressive advancement in CT technology over the past 10 years; leading to increased spatial and temporal resolution, decreased scan times and substantial reductions in radiation dose. Recent technological improvements have not only improved the status of CT coronary angiography but have also enabled new functional myocardial applications that are gaining a foothold in clinical practice as adjuncts or replacements for conventional coronary angiographic studies. Wide-detector CT designs along with prospective ECG-triggered protocols have opened the possibility of performing multiple complementary myocardial

measurements during a coronary CT exam with acceptable radiation see more and contrast exposure. In this Review, we discuss recent technical developments in cardiac MDCT and outline newly enabled noncoronary cardiac applications including viability assessment, myocardial perfusion and molecular imaging.”
“Microarray techniques have revolutionised genomic research by making it possible to monitor the expression of thousands of genes in parallel. The Fuzzy C-Means (FCM) method is an efficient clustering approach devised for microarray data analysis. However, microarray data contains noise, which would affect clustering results. In this paper, we propose to combine the FCM method with the Empirical Mode Decomposition (EMD) for clustering microarray data to reduce the effect of the noise. The results suggest the clustering structures of denoised microarray data are more reasonable and genes have tighter association with their clusters than those using FCM only.

Data recorded for each patient

included; age, gender, rel

Data recorded for each patient

included; age, gender, religion, socioeconomic status, literacy level, type of family unit, marital status, type of dwelling unit, mode of injury and its exact mechanism, place of incident, level of cooking stove, extent of burns (%TBSA), presence of features of inhalation injury, number of patients affected in a single mishap, size of LPG cylinder used, length of hospital stay and mortality. Of 731 flame burn patients in this study, 395 (54%) were due to kerosene burns and 200 (27.4%) from LPG mishaps. Significantly, the majority of injuries, in both the groups, occurred in lower middle class families living as nuclear units, in a single room dwelling, without a separate kitchen. Majority of VS-6063 LPG burns (70.5%, 141 patients) resulted from a gas leak and 25.5% were from cooking negligence (51 patients). 50.5% of kerosene accidents were from ‘stove mishaps’ and 49% due to cooking negligence. In all kerosene accidents the stove was kept at floor level but in LPG group 20.6% had the stove placed on a platform. There was a slight difference in mean TBSA burns; MK-0518 mw 51% in kerosene group compared to 41.5% TBSA in LPG group. There were nine episodes in LPG group in which there were more than three burn victims admitted for treatment. Very importantly, 77%

patients in LPG group were from a large cylinder (14.2 kg), which uses a rubber connecting tube. Mortality in kerosene group (50.6%) was far higher than in LPG group (33.5%). This study, from 200 LPG burn admissions, for the first time

details the profile from LPG mishaps. It is very interesting to note that of all burns in the world the inequitable distribution bias towards LMICs (low and middle income countries) extends further towards low middle class families within the LMIC. A major risk factor is constrained living condition of a single room dwelling unit. Almost all burns from LPG mishaps were potentially preventable if more care had been practiced to ensure safety. Since majority of LPG mishaps were from gas leaks, either from the rubber tube (Fig. 1) or the stove valve, www.selleckchem.com/products/bindarit.html the observation of floor level cooking in 79.4% of LPG cases may be an economic compulsion of a single room dwelling unit without much impact on the injury pattern. The small LPG cylinder (5 kg) in which the burner is placed directly over the cylinder, as one unit without a connecting tube, is safer because it reduces the chances of a gas leak from an ill-fitting or a cracked rubber connecting tube (Fig. 2). (C) 2011 Elsevier Ltd and ISBI. All rights reserved.”
“We introduce an extensible and modifiable knowledge representation model to represent cancer disease characteristics in a comparable and consistent fashion. We describe a system, MedTAS/P which automatically instantiates the knowledge representation model from free-text pathology reports.


“Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myo


“Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy (BM), and Congenital Myosclerosis are diseases caused by mutations in the genes encoding the extracellular matrix protein collagen AZD1480 solubility dmso VI. A dystrophic mouse model, where collagen VI synthesis was prevented by targeted inactivation of the Col6a1 gene, allowed the investigation of pathogenesis, which revealed the existence of a Ca2+-mediated dysfunction of mitochondria and sarcoplasmic reticulum, and of defective autophagy. Key events are dysregulation of the mitochondrial permeability transition pore, an inner membrane high-conductance channel that for prolonged open times

causes mitochondrial dysfunction, and inadequate removal of defective mitochondria, which amplifies the

damage. Consistently, the Col6a1(-/-) myopathic mice could be cured through inhibition GF120918 of cyclophilin D, a matrix protein that sensitizes the pore to opening, and through stimulation of autophagy. Similar defects contribute to disease pathogenesis in patients irrespective of the genetic lesion causing the collagen VI defect. These studies indicate that permeability transition pore opening and defective autophagy represent key elements for skeletal muscle fiber death, and provide a rationale for the use of cyclosporin A and its nonimmunosuppressive derivatives in patients affected by collagen VI myopathies, a strategy that holds great promise for treatment.”
“Prolonged use of immunosuppressive medication to avoid surgery is becoming more common in patients with inflammatory bowel disease, with severe or fulminant colitis. The effect of immunosuppression on postoperative outcomes was reviewed.\n\nPatients undergoing subtotal colectomy (STC) for fulminant or toxic colitis from 1992 to 2006 were studied to define the effect of immunosuppression (IS) on postoperative complications (POCs). Patient

characteristics, diagnosis, operative indication, details of surgery, use of IS, and POC’s were reviewed and univariate and multivariate analysis was performed.\n\nEighty-nine patients were studied (55 males). Seventy-two (91%) patients had fulminant colitis and 17 (20%) had toxic colitis. The preoperative diagnosis was ulcerative colitis in 74, indeterminate in 10, and Crohn’s disease in five patients. Eighty-two Poziotinib manufacturer (92%) patients were on some form of immunosuppression, and 14 had a perforation at surgery. Thirty-nine (43.8%) patients experienced a POC. There was no operative mortality. Univariate analysis identified perforation (P = 0.048) and length of surgery (P = 0.002) as predictive of POCs, while multivariate analysis failed to identify a predictor of complications.\n\nThere was no association between immunosuppression and postoperative complications. Complications in this setting are a result of the severity of the inflammatory bowel disease.”
“The general population is concerned about the probable devastating effects of pandemic H1N1 2009.

Further results confirmed that standardization of H2O2 measuremen

Further results confirmed that standardization of H2O2 measurements in EBC requires (1) the re-calculation of the concentration exhaled per 100 l exhaled breath (because the analyzed NCT-501 solubility dmso concentration in the liquid condensate underlies multiple methodological sources of variability given by the collection process), and (2) subtracting the concentration of inspired indoor H2O2. In the study on pH use of the ISFET electrode (Sentron, the Netherlands) and a blood gas analyzer

ABL 550 (Radiometer, Denmark) led to comparable results for EBC-pH (r=0.89, R-2=79.3%, p <= 0.001). Physiological pH data in non-degassed EBC samples varied between 5.3 and 6.5, and were not significantly different between subjects, but were significantly higher in the evening compared with the morning. EBC-pH was not dependent on variables of spontaneous breathing pattern or ambient conditions, and no significant correlation was found between serum and EBC for pH.”
“Background: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug

resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment Selleck CP 868596 is therefore essential to achieve a stable and long-lasting remission.\n\nMethods: Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative

PCR for mRNA expression, western blot for protein expression and quantitative and qualitative promoter methylation methods.\n\nResults: Combinations of melatonin and chemotherapeutic drugs (including temozolomide, current treatment for malignant gliomas) have a synergistic toxic effect on BTSCs and A172 malignant glioma cells. This effect is correlated with a downregulation of the expression and function of the ABC transporter ABCG2/BCRP. Melatonin increased the methylation levels of the ABCG2/BCRP promoter and the effects on ABCG2/BCRP expression and function were prevented by preincubation with a DNA methyltransferase inhibitor.\n\nConclusion: Our results point out a possible relationship between the downregulation of ABCG2/BCRP function and the synergistic toxic effect of melatonin and Selleck GSI-IX chemotherapeutic drugs. Melatonin could be a promising candidate to overcome multidrug resistance in the treatment of glioblastomas, and thus improve the efficiency of current therapies.”
“The interannual variation of the Bowen ratio, through its effect on the warming extent of available energy to the ecosystem land surface air, heavily influences the ecosystem microclimate and affects the hydrological cycle at both regional and global scales. Although the precipitation amount in southeast China is not expected to change greatly as a result of climate change, the precipitation frequency may be altered in the future.

Margins wider than the internal target volume as defined by 4DCT

Margins wider than the internal target volume as defined by 4DCT were required to encompass nearly all the motion detected by cine-MRI for some of the patients in this study. (C) 2015 Elsevier Inc. All rights reserved.”
“The role of P-glycoprotein (P-gp, ABCB1) on the absorption process

was investigated by drug-drug interaction studies of TAK-427 with P-gp inhibitors (erythromycin, ketoconazole or quinidine) in rats and by transport studies using rat multidrug resistance (MDR1) stably expressing Acalabrutinib research buy cells and rat small intestine mounted in a Ussing-type chamber. TAK-427 showed high efflux activity with low permeability in rat MDR1a and MDR1b stably expressing cells and was revealed to be a typical substrate for P-gps. Although TAK-427 was mainly absorbed from the small intestine in rats, a large part of the dosed compound remained in the gastrointestinal tract. PXD101 order Orally co-administered P-gp inhibitors (50 mg/kg) increased the AUC of TAK-427 after a 5 mg/kg oral dose 5.4- to

18.3-fold, whereas orally administered P-gp inhibitors had a minor effect on the increase in the AUC of TAK-427 (1.3- to 2.2-fold) after a 0.5 mg/kg intravenous dose. Thus, the bioavailability of TAK-427 after oral administration in rats (7.3%) markedly increased when co-administered with P-gp inhibitors (28.6-57.6%). Moreover, the transport of TAK-427 was predominantly secretory throughout the rat small intestine and was inhibited MLN4924 chemical structure by P-gp inhibitors. In conclusion, P-gp can markedly reduce the absorption of a typical P-gp substrate by its efflux activity throughout the absorption site. Copyright (C) 2008 John Wiley & Sons, Ltd.”
“The tumor necrosis factor (TNF) superfamily includes death receptor (DR) ligands, such as TNF-alpha, FasL, and TRAIL Death receptors (DRs) induce intracellular signaling upon engagement of their cognate DR ligands, either leading to apoptosis, survival, or proinflammatory responses.

The DR signaling is mediated by the recruitment of several death domain (DD)-containing molecules such as Fas-associated death domain (FADD) and receptor-interacting protein (RIP) 1. In this review, we describe DR signaling in mammals, and describe recent findings of DR signaling during metamorphosis in the African clawed frog Xenopus laevis. Specifically, we focus on the cell fate (apoptosis or survival) mediated through a DR ligand, TNF-alpha or TRAIL in endothelial cells or red blood cells (RBCs). In addition, we discuss relationships between thyroid hormone-induced metamorphosis and DR signaling. (c) 2012 Elsevier Inc. All rights reserved.”
“Study Type Therapy (case control) Level of Evidence 3b What’s known on the subject? and What does the study add? Abnormal pelvic floor muscle function has been associated with chronic pelvic pain syndromes. This study adds evidence about pelvic muscle performance in women with dry overactive bladders.

The authors hypothesised that polymorphisms in genes whose expres

The authors hypothesised that polymorphisms in genes whose expression were altered by gastroenteritis might be

linked to IBS with diarrhoea (IBS-D) which closely resembles PI-IBS.\n\nDesign Part 1: 25 healthy volunteers (HVs), 21 patients 6 months after Campylobacter jejuni infection, 37 IBS-D and 19 IBS with constipation (IBS-C) underwent rectal biopsy for gene expression analysis and peripheral blood mononuclear cell cytokine production assessment. Part 2: Polymorphisms in genes whose expression was altered in Part 1 were assessed in 179 HV, 179 IBS-D, 122 IBS-C and 41 PI-IBS.\n\nResults Part 1: Mucosal expression of seven genes was altered in IBS: CCL11, CCL13, Calpain 8 and TNFSF15 increased while NR1D1, GPR161 and GABRE decreased with similar patterns after check details infection with C jejuni. Part 2: The authors assessed 21 known single nucleotide polymorphisms (SNPs) in these seven genes and one SNP in each of the TNF alpha and IL-10 genes. Three out of five TNFSF15 SNPs (rs6478108,

rs6478109 and rs7848647) showed reduced minor allele frequency (MAF) (0.28, 0.27 and 0.27) in subjects with IBS-D compared with HV (0.38, 0.36 and 0.37; p=0.007, 0.015 and 0.007, respectively) confirming others recent findings. The authors also replicated the previously reported association of the TNFa SNP rs1800629 with PI-IBS which showed an increase in the MAF at 0.30 versus 0.19 for HV (p=0.04).\n\nConclusion NVP-BKM120 IBS-D and PI-IBS patients are associated with TNFSF15 and TNFa genetic polymorphisms which also predispose to Crohn’s disease suggesting possible common underlying pathogenesis.”
“We performed a two-stage genome-wide association study

of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up selleck inhibitor of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 x 10(-11), OR = 1.21; rs4227, P = 4.31 x 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 x 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and alpha-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 x 10(-20), OR = 1.34; rs1794275, P = 3.43 x 10(-13), OR = 1.30; rs2523946, P = 1.74 x 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 x 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

To test how these components are influenced by social setting and

To test how these components are influenced by social setting and predictive value of feedback information, we compared event-related potentials, as well as their topographies and neural generators, for performance feedback generated by oneself and others in a cooperative versus competitive context. Our results show that (1) the predictive relevance of outcomes is crucial to elicit an FRN in both players and observers, (2) cooperation increases FRN and

P300 amplitudes, especially in individuals with high traits of perspective taking, and (3) contrary to previous findings on gambling outcomes, oFRN components are generated for both cooperating and competing observers, but with smaller amplitudes in the latter. Neural source estimation revealed medial prefrontal activity for both FRN and oFRN, but with additional BAY 57-1293 supplier generators for the oFRN in the dorsolateral and ventral prefrontal cortex, as well as the temporoparietal junction. We conclude that the latter set of brain regions could mediate social influences on action monitoring by representing agency and social relevance of outcomes

and are, therefore, recruited in addition to shared prediction error signals generated in medial frontal areas during action outcome observation.”
“Objective: To describe human capacity and staff movement in national health research institutions in 42 sub-Saharan African countries. Design: A structured questionnaire was used to solicit information on governance and stewardship from health research institutions. Setting: Eight hundred and forty-seven health research institutions in 42 sub-Saharan African countries. Participants: Key informants from 847 health CA3 concentration research institutions. Main outcome measures: The availability, mix and quality of human resources in health research institutions. Results: On average, there were 122 females employed per respondent health research institution, compared with 159 males. For researchers, buy GS-9973 the equivalent figures were nine females to 17 males. The

average annual gross salary of researchers varied between US$ 12,260 for staff with 5-10 years of experience and US$ 14,772 for the institution head. Of those researchers who had joined the institution in the previous 12 months, 55% were employed on a full-time basis. Of the researchers who left the institutions in the same period, 71% had a full-time contract. Among all those who left, those who left to a non-research sector and to another country accounted for two-thirds. Conclusions: The study revealed significant gaps in the area of human capacity development for research in Africa. The results showed a serious shortage of qualified staff engaged in health research, with a dearth of staff that held at least a master’s degree or doctoral degree. Major efforts will be required to strengthen human resource capacity, including addressing the lack of motivation or time for research on the part of existing capable staff.