In regard to their clinical effects, sSMCs

In regard to their clinical effects, sSMCs PARP inhibitor are a heterogeneous group: in particular, sSMCs containing pericentromeric euchromatin are likely to be associated with abnormal outcomes, although exceptions have been reported. To improve characterization of the genetic content of sSMCs, several approaches might be applied based on different molecular and molecular-cytogenetic assays, e. g., fluorescent in situ hybridization (FISH), array-based comparative genomic hybridization (array

CGH), and multiplex ligation-dependent probe amplification (MLPA).

To provide a complementary tool for the characterization of sSMCs, we constructed and validated a new, FISH-based, pericentromeric Bacterial Artificial Chromosome (BAC) clone set that with a high resolution spans the most proximal euchromatic sequences of all human chromosome

arms, excluding the acrocentric short arms.

Results: By FISH analysis, we assayed 561 pericentromeric BAC probes and excluded 75 that showed a wrong chromosomal localization. The remaining 486 probes were used to establish 43 BAC-based pericentromeric panels. Each panel consists of a core, which with a high resolution covers the most proximal euchromatic similar to 0.7 LY2835219 cell line Mb (on average) of each chromosome arm and generally bridges the heterochromatin/euchromatin junction, as well as clones located proximally and distally to the core. The pericentromeric clone set was subsequently validated by the characterization of 19 sSMCs. Using

the core probes, we could rapidly distinguish between heterochromatic (1/19) and euchromatic (11/19) sSMCs, and estimate the euchromatic DNA content, which ranged from approximately 0.13 to more than 10 Mb. The characterization was not completed for seven sSMCs due to a lack of information about the covered region in the reference sequence (1/19) or sample insufficiency (6/19).

Conclusions: Our results demonstrate that this pericentromeric clone set is useful as an alternative tool for sSMC characterization, primarily in PD-1/PD-L1 Inhibitor 3 nmr cases of very small SMCs that contain either heterochromatin exclusively or a tiny amount of euchromatic sequence, and also in cases of low-level or cryptic mosaicism. The resulting data will foster knowledge of human proximal euchromatic regions involved in chromosomal imbalances, thereby improving genotype-phenotype correlations.”
“Spherical magnetic iron particles were milled into different flake shapes, and their permittivity, permeability dispersion behaviors have been investigated within the frequency range of 1-8 GHz range. The results show that both permittivity and permeability values depend on the particle shapes. These flake particles also demonstrate better microwave absorption performances. (C) 2010 American Institute of Physics. [doi:10.1063/1.3367970]“
“Introduction: Implantable cardioverter defibrillators (ICD) significantly reduce mortality in patients with left ventricular (LV) dysfunction.

05), the composite of death, any CV event and revascularization (

05), the composite of death, any CV event and revascularization (-16%; P < 0.05) and coronary angiography (-22%; P < 0.01). These benefits were achieved with relatively small differences in systolic (3.2 mm Hg) and diastolic blood pressure (BP) (2.3 mm Hg). In 2303 patients (30.0%) who had ISH at baseline (1145 nifedipine GITS and 1158 placebo), nifedipine significantly reduced the primary efficacy end point

(-18%; P < 0.03), any CV event (-22%; P < 0.01) and new heart failure (-40%; P < 0.01). The benefits were associated with between-group differences in achieved BP of 4.7 and 3.3 mm Hg for systolic and Z-VAD-FMK nmr diastolic BP, respectively. In summary, the lowest CV event rates were seen in those receiving (i) the combination of RAS click here blockade and nifedipine GITS and (ii) in those specifically treated

for ISH. Journal of Human Hypertension (2011) 25, 63-70; doi:10.1038/jhh.2010.19; published online 25 February 2010″
“The interactions between two heme proteins myoglobin (HMb) and horseradish peroxidase (HRP) with zinc oxide (ZnO) nanoparticles are investigated by using UV-vis absorption, steady state fluorescence, synchronous fluorescence, time-resolved fluorescence, FT-IR, atomic force microscopy (AFM) and circular dichroism (CD) techniques under physiological condition of pH similar to 7.4. The presence of mainly static mode in fluorescence quenching mechanism of HMb and HRP by ZnO nanoparticle indicates the possibility of formation of ground state selleck products complex. The processes of bindings of ZnO nanoparticles with the two proteins are spontaneous molecular interaction procedures. In both cases

hydrogen bonding plays a major role. The circular dichroism (CD) spectra reveal that a helicity of the proteins is reduced by increasing ZnO nanoparticle concentration although the alpha-helical structures of HMb and HRP retain their identity. On binding to the ZnO nanoparticles the secondary structure of HRP molecules (or HMb molecules) remains unchanged while there is a substantial change in the environment of the tyrosin active site in case of HRP molecules and tryptophan active site in case of HMb molecules. Tapping mode atomic force microscopy (AFM) was applied for the investigation the structure of HRP adsorbed in the environment of nanoparticles on the silicon and on the bare silicon. HRP molecules adsorb and aggregate on the mica with ZnO nanoparticle. The aggregation indicates an attractive interaction among the adsorbed molecules. The molecules are randomly distributed on the bare silicon wafer. The adsorption of HRP in the environment of ZnO nanoparticle changes drastically the domains due to a strong interaction between HRP and ZnO nanoparticles. Similar situation is observed in case of HMb molecules.

Cases We present two cases of parous women with complaint of amen

Cases We present two cases of parous women with complaint of amenorrhea and mild bleeding. Sonography and magnetic resonance imaging (MRI) revealed the diagnosis of CSP without viable gestational sac. The patients opted for expectant treatment. We closely monitored the patients with a detailed plan.

Results In case 1, the patient had mild VX-680 bleeding during monitoring and her serum beta HCG dropped quickly to normal range after 7 weeks. She was fully recovered with total absorption of the mixed mass in the scar of the anterior wall of the uterus. In case 2, the patient had laparoscopy after expectant management for 16 weeks

because her serum beta HCG reached a plateau between 30 and 40 mIU/mL for 4 weeks and there was no obvious resorption of the mixed mass within the lower anterior wall of the uterus. The histopathology revealed decidualized villa within organizing tissue and the patient recovered uneventfully.

Conclusions CSP with no viable gestation Apoptosis inhibitor sac and rapidly decreased serum beta HCG level can be expectantly treated. The natural history of such CSPs may be naturally demised.”
“This study reports an appreciable yield of podophyllotoxin (PDT) in P. hexandrum plants grown ex situ under polyhouse conditions of a temperate locale. The PDT content

of below-ground parts was affected by both plant age and growth period. However, only the effect of plant age on PDT content was significant. Thus, the highest amounts of PDT were recorded in the below-ground parts of 2-year-old plants harvested during the late-growth period (LGP). High total soluble sugars in the below-ground parts during the early growth period (EGP) and the highest nitrate and nitrate reductase in the leaves of 2-year-old plants during the peak-growth period (PGP) indicated higher mobilization and assimilation of starch and nitrate. Probably the surplus carbon and nitrogen gained during the PGP were diverted

from aerial parts to below-ground parts during the LGP and in turn contributed to the synthesis of higher amounts of PDT. This study shows that commercial selleckchem cultivation of P. hexandrum is possible under ex situ temperate conditions.”
“We investigate the strain profiles and electronic structures of a novel quantum ring capped by a material different from the substrate. By comparing the novel quantum ring with an ordinary quantum dot and quantum ring, which are capped by the same material as the substrate, we find that the novel quantum ring exhibits noticeably different properties, such as an anomalous strain relaxation, band alignments, and blueshift of the emission energy. We investigate the novel properties of our quantum ring by separating the ring evolution process into (i) the step of geometric change from a dot to ring and (ii) the step of GaAs capping. The GaAs embedded in the In0.53Ga0.


Of 1,832 catheter ablation procedures performed


Of 1,832 catheter ablation procedures performed during a 5-year period, 10 (0.55%) were complicated by cardiac tamponade. Fluoroscopic examination confirmed the diagnosis in all 10 patients and demonstrated GANT61 inhibitor effusions before hypotension in four patients. All patients were stabilized by fluoroscopy-guided pericardiocentesis with placement of an indwelling catheter and autologous transfusion. The time interval between recognition of cardiac tamponade and completion of pericardiocentesis was 6.0 +/- 1.8 minutes (range 3-9 minutes). The mean aspirated blood volume was 437 mL (range 110-1,400 mL), and the mean autotransfused blood volume was 425 mL (range 100-1,384 mL). Surgical repair of the cardiac perforation was needed in one patient. No procedure-related death occurred.

Conclusion: A reduction in the excursion of cardiac silhouette on fluoroscopy is an early diagnostic sign of cardiac tamponade during radiofrequency ablation. Fluoroscopy-guided pericardiocentesis is a safe and effective management strategy for cardiac tamponade developed in the cardiac catheterization laboratory. (PACE 2011; 9-14).”
“Study Design. Case report.

Objective. To describe a patient with nodular fasciitis in the sciatic nerve, detected Natural Product Library mw by positron emission tomography (PET).

Summary of Background Data. Severe sciatic

pain is commonly caused by lumbar disc herniation, lumbar spinal stenosis, or neoplastic lesion.

These lesions are usually diagnosed by plain radiograph, myelography, computed tomography, and magnetic resonance imaging.

Nodular fasciitis is a benign connective tissue tumor usually presenting as a firm, rapidly-growing lesion, occasionally arising in the forearm. Only 5 cases of intraneural nodular fasciitis have been reported in the published data, and although some have demonstrated mild neuropathy, none have shown nodular fasciitis with intractable sciatica.

Methods. A 37-year old woman experienced severe sciatica after hitting her left buttock hard on the edge of a bathtub. Physical examination demonstrated intense radiating pain from the left buttock to the lateral calf. There was weakness in the sciatic nerve innervated musculature. JPH203 She was diagnosed with piriformis syndrome in a local hospital. However, the symptoms remained unchanged after surgery, releasing the piriformis. Conventional imaging of the sciatica including plain radiograph, computed tomography, and magnetic resonance imaging of the spine showed a return of abnormal findings.

Results. PET detected an abnormal lesion in the sciatic nerve in the posterior compartment of the patient’s left thigh, indicating an intraneural tumor in the sciatic nerve. Subtotal resection was achieved and histologic evaluation of the specimen showed the typical features of nodular fasciitis.

[doi:10 1063/1 3658809]“
“An epigenetic control of vernaliza

“An epigenetic control of vernalization has been demonstrated in annual plants such as Arabidopsis and cereals, but the situation remains unclear in biennial plants such as sugar beet that has an absolute requirement for vernalization.

The role of DNA methylation in flowering induction Autophagy inhibitor research buy and the identification of corresponding target loci also need to be clarified. In this context, sugar beet (Beta vulgaris altissima) genotypes differing in bolting tolerance were submitted to various bolting conditions such as different temperatures and/or methylating drugs. DNA hypomethylating treatment was not sufficient to induce bolting while DNA hypermethylation treatment inhibits and delays bolting. Vernalizing and devernalizing temperatures were shown to affect bolting as well as DNA methylation levels in the shoot apical meristem. In addition, a negative correlation was established between bolting and DNA methylation. Genotypes considered as resistant or sensitive to bolting could also be distinguished by their DNA methylation levels. Finally, sugar beet homologues of the Arabidopsis vernalization genes FLC and VIN3 exhibited distinct DNA methylation marks during vernalization independently to the variations of global DNA methylation. These vernalization SBI-0206965 solubility dmso genes also displayed differences in mRNA accumulation and methylation

profiles between genotypes resistant or sensitive to bolting. Taken together, the data suggest that the time course and amplitude of DNA methylation variations are critical points for the induction of sugar beet bolting and represent an epigenetic component of the genotypic bolting tolerance, opening up new perspectives for sugar beet breeding.”
“Aggarwal S, Bane BC, Boucek CD, Planinsic RM, Lutz JW, Metro DG. Simulation: a teaching tool for liver transplantation Wnt activity anesthesiology. Abstract: Anesthesia for liver transplantation (ALT) requires extensive preparation and rapid recognition of changing clinical conditions. Owing to the proliferation of transplant centers, greater number of anesthesia providers need training in specific skills required to treat

these patients. These cases are no longer limited to few transplant centers; therefore, reduction of cases in individual centers has created a need for simulation training to prepare and supplement clinical experience. We have developed an ALT simulation course for senior anesthesia residents which combines didactic sessions with live-patient-based and mannequin-based simulation. Outcomes have been measured using pre- and post-simulation course quizzes as well as a survey given at the end of the month-long ALT rotation. Twenty-four senior anesthesiology residents (n = 24) have completed the ALT simulation course. Residents had an average score of 75% +/- 10% on the pre-simulation quiz, which increased to 92% +/- 6.5% on the post-simulation quiz (p < 0.001).

7 +/- 7 9 years) underwent trans-apical LV lead implantation Epi

7 +/- 7.9 years) underwent trans-apical LV lead implantation. Epicardial LV leads were implanted in 12 end-stage HF patients (group II; mean age 62.8 +/- 7.3 years). Medical therapy was optimized in all patients. The

following parameters were compared during an 18-month follow-up period: LV ejection fraction (LVEF), LV end-diastolic diameter (LVEDD), LV end-systolic diameter, and New York Heart Association (NYHA) functional class.

Results: Nine out of 11 patients responded favorably to the treatment in group I (LVEF 39.7 +/- 12.5 vs 26.0 +/- 7.8%, P < 0.01; LVEDD 70.4 +/- 13.6 mm vs 73.7 +/- 10.5 mm, P = 0.002; NYHA class 2.2 +/- 0.4 vs 3.5 +/- 0.4, P < 0.01) and eight out of 12 in group II (LVEF 31.5 +/- 11.5 vs 26.4 +/- 8.9%, P = < 0.001; NYHA class 2.7 +/- GW4869 cell line 0.4 vs 3.6 +/- 0.4, P < 0.05). During the follow-up period, one patient died in group I and three in group II. There was one intraoperative LV lead dislocation in group I and one early postoperative dislocation in each group. None of the patients developed thromboembolic complications.

Conclusions: Our data suggest that trans-apical endocardial LV lead implantation is an alternative to epicardial LV pacing. (PACE 2012;35:124-130)”
“Background: The objective

of this study is to analyze the spatial selleck kinase inhibitor and temporal patterns of malaria incidence as to determine the means by which climatic factors such as temperature, rainfall and humidity affect its distribution in Maputo province, Mozambique.

Methods: This study presents a model of malaria that evolves in space and time in Maputo province-Mozambique, over a ten years period (1999-2008). The model RG-7112 order incorporates malaria cases and their relation to environmental variables. Due to incompleteness of climatic data, a multiple imputation technique is employed. Additionally, the whole province is interpolated through a Gaussian process. This method overcomes the misalignment problem of environmental variables (available at meteorological stations points) and malaria cases (available

as aggregates for every district – area). Markov Chain Monte Carlo (MCMC) methods are used to obtain posterior inference and Deviance Information Criteria (DIC) to perform model comparison.

Results: A Bayesian model with interaction terms was found to be the best fitted model. Malaria incidence was associated to humidity and maximum temperature. Malaria risk increased with maximum temperature over 28 degrees C (relative risk (RR) of 0.0060 and 95% Bayesian credible interval (CI) of 0.00033-0.0095) and humidity (relative risk (RR) of 0.00741 and 95% Bayesian CI 0.005141-0.0093). The results would suggest that additional non-climatic factors including socio-economic status, elevation, etc. also influence malaria transmission in Mozambique.

We anticipate our study to be a starting point for animal experim

We anticipate our study to be a starting point for animal experiments that test navigation in perceptually CX-6258 ambiguous environments.”

and objectives: Physical fitness level is a marker of cardiovascular health in young people. The aim of this study was to analyze the effects of a school-based intervention program, focused on increasing the volume and intensity of physical education (PE) sessions, on adolescents’ physical fitness.

Methods: Sixty-seven adolescents (12-14 years old) from three secondary school classes participated in a 16-week intervention. The classes were randomly allocated to the control group, experimental group 1 (EG1) or experimental group 2 (EG2). The control group received standard PE (2 sessions/week), the EG1 received 4 standard PE sessions/week and the EG2 received four high-intensity PE sessions/week. Aerobic fitness, muscle strength, speed-agility and flexibility were assessed using previously validated field-based tests before and after the intervention.

Results: Doubling the number of PE sessions/week resulted in improvements learn more in aerobic fitness and flexibility (P = .008 and P = .04, respectively). Further increases in the intensity of the sessions were related to improvements in speed-agility (P < .001). The maximal oxygen consumption

increased by 3 and 5 mL/kg/min in the EG1 and EG2, respectively. No differences were observed for muscle strength.

Conclusions: The results suggest that doubling the frequency of PE sessions is a sufficient stimulus to improve physical fitness, particularly aerobic fitness, which has been shown to be a powerful indicator of cardiovascular health in children and adolescents. Future studies involving larger sample sizes should GSK1210151A confirm or refute these findings. (C) 2011 Sociedad Espanola de Cardiologia.

Published by Elsevier Espana, S.L. All rights reserved.”
“Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the brain tumors during neurosurgical operations. The individual features of the cells sensitivity of primary cultures in respect to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6) level in the culture medium after the application of chemotherapy were established. The initial level of Il-6 exceeded 600.0 pg/ml in the cultural medium with histologically verified pilomyxoid astrocytoma cells, and ranged from 100.0 to 200.0 pg/ml in the medium at cultivation of ganglioneuroblastoma and pilocytic astrocytoma. A decrease in the Il-6 level in the medium culture of primary tumors cells was observed after the application of chemotherapeutic agents on the cells of pilomyxoid astrocytoma, astrocytomas, and pilocytic desmoplastic/nodular medulloblastoma.

Age, congestive heart failure, and emergency surgery were

Age, congestive heart failure, and emergency surgery were

independent risk factors for the development of delirium after major surgery.”
“Total phenolic compounds (TPC) and antioxidant activities using different assays (DPPH, ABTS and ORAC) in fruits, grains, leaves, seeds, roots and tubers from 27 different Peruvian Andean plants used in folk medicine or/and as food by the native population were evaluated in order to use these as natural antioxidant compounds. Total flavanoids (TFA), total flavonoids (TFO) and total anthocyanins (TA) were also determined. In general, the samples with the highest TPC values had the highest antioxidant activities. Leaves (e.g., Alnus acuminate, Clinopodium bolivianum, Lepechinia meyenii (Walp) and Mutisia acuminate), fruits (e.g., Sambucus peruviana), tubers (e.g., Tropaeolum

tuberosum) and seed (e.g., Lupinus mutabilis) sparked attention due to their high TPC and antioxidant activities. Results from this study highlight the biodiversity of the Andean Region of Peru where plants with high TPC and antioxidant properties grow. Thus, these plants can be considered as promising sources of antioxidant phytochemicals. (c) 2013 Elsevier B.V. All rights reserved.”
“Anaphylaxis is a severe, life-threatening, systemic allergic reaction that is almost always unanticipated and may lead to death by airway obstruction or vascular collapse. Anaphylaxis occurs as the result of an allergen response, usually immunoglobulin E mediated, which leads to mast cell BGJ398 chemical structure and basophil activation and a combination of dermatologic, respiratory, cardiovascular, gastrointestinal, and neurologic symptoms. Dermatologic and respiratory symptoms are most common, occurring in 90 and 70 percent of episodes, respectively. The three most common triggers are food, insect stings, and medications. The diagnosis of anaphylaxis is typically made when symptoms occur within one hour of exposure to a specific antigen. Confirmatory testing using serum histamine and tryptase levels is difficult, because

see more blood samples must be drawn with strict time considerations. Allergen skin testing and in vitro assay for serum immunoglobulin E of specific allergens do not reliably predict who will develop anaphylaxis. Administration of intramuscular epinephrine at the onset of anaphylaxis, before respiratory failure or cardiovascular compromise, is essential. Histamine H, receptor antagonists and corticosteroids may be useful adjuncts. All patients at risk of recurrent anaphylaxis should be educated about the appropriate use of prescription epinephrine autoinjectors. (Am Earn Physician. 2011;84 (10):111-11118. Copyright (C) 2011 American Academy of Family Physicians.)”
“Introduction: There are potential benefits of percutaneous over open femoral access for endovascular aneurysm repair (EVAR).

9%, 13 3% and 39 3% Severity of ARF correlated with

9%, 13.3% and 39.3%. Severity of ARF correlated with learn more development of CKD: stage 3 was associated with all classes of ARF, stages 4 and 5d only with severe ARF. Hemodialysis requirement (23%) and mortality were only correlated with the most severe

form of ARF (F class). In conclusion, RIFLE classification is a useful tool to stratify the severity of early ARF providing a prognostic indicator for the risk of CKD occurrence and death.”
“This paper details pulsed gradient NMR measurements of the (3)He diffusion coefficient in sealed cells during spin exchange optical pumping. The potential of ultra low field magnetic resonance imgaing (MRI) and NMR for noninvasive measurement of cell pressure is demonstrated. Diffusion sensitization gradients

allow measurement of the (3)He diffusion coefficient from which the pressure and/or temperature of the gas can be determined during optical pumping. The pressure measurements were compared with neutron time of flight transmission measurements. GW4869 cost Good agreement was observed between the temperature/pressure measurements and predictions based on Chapman-Enskog theory. The technique had sufficient sensitivity to observe the diffusion coefficient increasing with temperature in a sealed cell. With this method, evidence for laser heating of the (3)He during optical pumping was found. The results show that NMR diffusion measurements allow noninvasive measurement of the cell temperature and/or pressure in an optical pumping setup. The method can be expanded using MRI to probe the spatial distribution of the diffusion coefficient. These techniques can be applied to the further investigation of polarization limiting effects such as laser

heating. (c) 2010 American Institute of Physics. [doi:10.1063/1.3371249]“
“ObjectivePhysical SRT2104 in vitro activity (PA) has been shown to provide health benefits for breast cancer patients. The effects of augmenting oncology healthcare provider (HCP) advice for PA with 3months of telephone counseling versus contact control were evaluated in a randomized trial. Our goal in this secondary analysis was to examine the amount of PA (min/week) needed for psychosocial benefits among both groups.

MethodsAfter receiving brief HCP advice to become physically active, 192 women (age in years: mean=60.0, SD=9.9) who had completed treatment for Stage 0-IV breast cancer were randomized to telephone counseling to support PA (n=106) or contact control (n=86). Their PA, fatigue, physical functioning, and quality of life were assessed at baseline (before receiving HCP advice), 3, 6, and 12months. A non-randomized design was used to examine the dose-response relationship between PA and psychosocial outcomes.

ResultsExercising for at least 150min/week at moderate intensity was associated with improved physical functioning (b=5.9, SE=2.9, p=0.04) and quality of life (b=3.6, SE=1.9, p=0.05) at 3months. These relationships were not found at 6 and 12months (p’s>0.05).

For all of these countries, the estimated cost-utility ratio is w

For all of these countries, the estimated cost-utility ratio is well below typical benchmark values and these ratios are robust, as demonstrated by one-way sensitivity and variability analyses and multi-way probabilistic sensitivity analyses.

Studies using other metrics including the average 1-year drug cost per patient

with a plasma selleck chemical HIV-RNA level less than 50 copies/mL at 48 weeks, the incremental drug cost per additional patient with a plasma HIV-RNA level less than 50 copies/mL at 48 weeks, the total (antiretroviral and non-antiretroviral) costs during the first year of treatment, and the total healthcare budget impact during the first 5 years of treatment provided further evidence of the positive economic outcomes with the use of DRV/r in treatment-experienced PLHIV.

Different measures of economic outcomes are useful for different types of decision-makers and different types of decisions. In general, the results of these different types of analyses will be consistent

with each other. For darunavir, the economic analyses Pevonedistat ic50 reviewed in this paper demonstrate that the use of DRV/r 600/100 mg bid in the management of HIV-infected, treatment-experienced adults who have failed at least one of the other currently available PIs is cost

effective and may be cost saving.”
“Strategies to change the existing mix of Innovative and ‘me-too’ drugs, are Intended to increase societal value of a given Investment in GSK1210151A supplier R&D by providing,in incentive for firms to Invest in drugs that are more likely to be clinically Innovative How can financial Incentives be used to change this mix? Win I strategy have its Intended consequence or win it have the unintended outcome of reducing the Nile at which the population burden of disease is reduced? The perspective of this review IS a country Such as Australia. Canada or the UK that has universal health insurance and a drug reimbursement process that is Informed by economic evidence.

A review of the literature was performed and the views of both the proponents and the opponents Of Such strategies and the mechanisms by which they Could be Implemented Were summarized The debate is based largely on hypothesized responses by firms to changes in incentives rather than empirical evidence The main ponit of contention is whether a changed mix of new molecular entities (NMEs) increases or decreases the total amount Of clinical innovation launched each year.

The argument presented in this article is that, despite the limited empirical evidence.