Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study.

Essentials We studied the C-reactive protein (CRP) gene on stroke risk in atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism genotype were followed-up for more than 10 years. Patients with the A-390/T-390 allele of the CRP gene were more likely to get ischemic stroke. The triallelic polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY: Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of thromboembolic stroke in patients with atrial fibrillation (AF). An increasing body of evidence is demonstrating that inflammatory responses play an important role in the pathophysiology of AF. Objectives To investigate the effect of genetic polymorphisms of the C-reactive protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF. Methods A total of 725 AF patients were longitudinally followed up for > 10 years; this is the largest and longest AF follow-up cohort with genetic data. CRP promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP levels were divided into four quartiles. Results Patients with higher CRP levels were more likely to develop thromboembolic stroke than those with lower CRP levels (P<0.001, log-rank test for comparison of four quartiles). After adjustment for conventional risk factors, patients with higher CRP levels were more likely to develop thromboembolic stroke than those in the lowest CRP quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the lowest CRP quartile was the reference group). Patients carrying the A-390 or T-390 allele had higher CRP levels (3.35 ± 2.71 mg L-1 versus 2.43 ± 2.00 mg L-1 ), and were more likely to develop thromboembolic stroke, even after adjustment for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP triallelic polymorphism and the CRP level are associated with the risk of incident thromboembolic stroke in patients with AF.

Immunologic assessment and KMT2D mutation detection in Kabuki syndrome.

Kabuki or Niikawa-Kuroki syndrome (KS) is a rare disorder with multiple malformations and recurrent infections, especially otitis media. This study aimed to investigate the genetic defects in Kabuki syndrome and determine if immune status is related to recurrent otitis media. Fourteen patients from 12 unrelated families were enrolled in the 9-year study period (2005-2013). All had Kabuki faces, cleft palate, developmental delay, mental retardation, and the short fifth finger. Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. Immunologic analysis revealed lower memory CD19+ cells (11/13), lower memory CD4+ cells (8/13), undetectable anti-HBs antibodies (7/13), and antibody deficiency (7/13), including lower IgA (4), IgG (2), and IgG2 (1). Naïve emigrant lymphocytes, lymphocyte proliferation function, complement activity, and superoxide production in polymorphonuclear cells were all normal. All the patients had KMT2D mutations and 10 novel mutations of R1252X, R1757X,Y1998C, P2550R fs2604X, Q4013X, G5379X, E5425K, R5432X, R5432W, and R5500W. Resembling the phenotype of common variable immunodeficiency, KS patients with antibody deficiency, decreased memory cells, and poor vaccine response increased susceptibility to recurrent otitis media. Large-scale prospective studies are warranted to determine if regular immunoglobulin supplementation decreases the frequency of otitis media and severity of hearing impairment.

Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.

OBJECTIVES: The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population. DESIGN, SETTING AND PARTICIPANTS: Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins. RESULTS: A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment. CONCLUSION: Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia.

The application of ultrasonic harmonic scalpel in the radical surgery of gastric cancer

PURPOSE: Ultrasonic harmonic scalpel has been widely applied to laparoscopic surgery of gastric cancer, but it has not been evaluated properly in open surgery. The objective of this study was to evaluate the value of the ultrasonic harmonic scalpel in the open radical surgery of gastric cancer. METHODS: 106 gastric cancer patients who had accepted distal D2 lymphadenectomy were included in this study. Patients were divided into ultrasonic harmonic scalpel (UHS) surgery group (50 cases) and conventional electric scalpel surgery group (56 cases). UHS surgery group patients were accepted surgery by ultrasonic harmonic scalpel. Instead, conventional electric scalpel surgery group patients were accepted surgery by monopolar electrocautery shovel and other traditional instruments. Then the average operation time, intra-operative blood loss, number of harvested lymph nodes, average post operative drainage within 3 days, and postoperative hospital stay were collected and compared between the two groups. RESULTS: The average operation time, blood loss, postoperative hospital stay in UHS group were significantly lower than traditional group (P < 0.05). The number of lymph node dissection was significantly higher than conventional surgery group (P < 0.05). There were no difference between two groups in average drainage within 3 days after surgery and the hospitalization costs (P > 0.05). In the presence of atherosclerotic patients, the average operation time, blood loss in UHS surgery group were significantly lower than the traditional group (P < 0.05). CONCLUSION: Ultrasonic harmonic scalpel may have better effect in the radical surgery of gastric cancer patients. It meets the requirements of the future development of precise surgical procedure (AU)

Clinical research in individual information of celiac artery CT imaging and gastric cancer surgery

OBJECTIVE: The objective of this study is to acquire CT images of the celiac artery by 64-multi-slice spiral CT angiography (64-MSCTA) in gastric cancer patients to facilitate gastric cancer surgery. METHODS: Preoperative 64-MSCTA was performed to observe the origin, course and anatomical variations of the celiac artery and vascular calcifications in 102 gastric cancer patients. RESULTS: (1) The celiac trunk mostly arose at the level between the 12th thoracic vertebra and the 1st lumbar vertebra; the mean inferior angle with the abdominal aorta was 63.5° (14°-159°), the mean length was 36.29 mm (5.80-73.58 mm), and its course showed many styles. (2) Of 102 gastric cancer patients, 34 patients (33.33 %) were observed with celiac artery variations of whom there were 27 patients with anatomical variations of the hepatic artery, 3 patients with anatomical variation of the left gastric artery and 1 patient with anatomical variation of the splenic artery; in 1 patient, the celiac trunk and the superior mesenteric artery originated from a common trunk. In other cases, it was observed with another variation. (3) The abdominal aortic calcified plaque was observed in 48 patients (47.1 %), and among them, 34 patients were more than 60 years old, and the existence of the abdominal aortic calcified plaque was related to age, significantly (P < 0.01). CONCLUSIONS: The 64-MSCTA largely improves our understanding of the origin, course and anatomical variations of the celiac artery and vascular calcifications in individual patient with gastric cancer. It is recommended that the 64-MSCTA of the celiac artery should be classified as a routine preoperative procedure in gastric cancer patients (AU)

Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Proliferation of myofibroblasts in the stroma of renal oncocytoma.

OBJECTIVES: Myofibroblasts are a vital component of stroma of many malignant neoplasms, but it is not yet established whether stromal myofibroblasts also exist in benign tumours such as oncocytoma of the kidney. MATERIALS AND METHODS: Histomorphological and immunohistochemical analysis of 16 renal oncocytomas diagnosed at Chang Gung Memorial Hospital, Taiwan, has been performed. RESULTS: Renal oncocytomas were composed of oncocytes, large cells with granular eosinophilic cytoplasm, arranged mostly in sheets, in tubulocystic or combined pattern. Few oncocytes appeared to be undergoing proliferation or apoptosis. MIB-1 and active caspase 3 indices were low, but higher in tumour than in surrounding non-tumour parenchyma (MIB-1: 0.93 +/- 0.09 versus 0.46 +/- 0.07, P < 0.001 and active caspase 3: 0.76 +/- 0.08 versus 0.41 +/- 0.09, P < 0.001). Wnt/beta-catenin signalling was not implicated in this neoplasm, as there was no loss of E-cadherin membranous localization or expression of intranuclear beta-catenin in the cells. Clumps of oncocytes were stained with periodic acid Schiff and had collagen I-, collagen III- and fibronectin-positive, but desmin- and human caldesmon-negative stromas. Importantly, alpha-smooth muscle actin (SMA)-immunostaining established the myofibroblastic nature of many of the stromal cells. Some of the myofibroblasts were also positive for MIB-1, indicating a proliferative role for them in the stroma. CONCLUSIONS: Renal oncocytomas were composed of two independent compartments: benign oncocytes and pronounced fibrotic stroma, which consisted of proliferating myofibroblasts (SMA- and MIB-1-positive) which were associated with excessive deposition of extracellular matrix (periodic acid Schiff-component, collagen I-, collagen III- and fibronectin-positive, and desmin- and human caldesmon-negative).

Rupture of mitral chordae tendineae: adding to the list of hypertension complications.

BACKGROUND: Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated. METHODS: 494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included. RESULTS: Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p<0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p<0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p<0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p<0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively. CONCLUSIONS: There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.

Renin-angiotensin system gene polymorphisms and diastolic heart failure.

BACKGROUND: Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. MATERIALS AND METHODS: A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT(1)R) gene were genotyped. RESULTS: In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT(1)R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT(1)R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. CONCLUSIONS: Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

Combination of baculovirus-expressed BMP-2 and rotating-shaft bioreactor culture synergistically enhances cartilage formation.

Baculovirus is an emerging gene delivery vector, thanks to a number of unique advantages. Herein, we genetically modified the rabbit articular chondrocytes with a recombinant baculovirus (Bac-CB) encoding bone morphogenetic protein-2 (BMP-2), which conferred high level BMP-2 expression and triggered the re-differentiation of dedifferentiated third passage (P3) chondrocytes in the monolayer culture. The transduced and mock-transduced P3 cells were seeded into porous scaffolds and cultured in either the dishes or the rotating-shaft bioreactor (RSB), a novel bioreactor imparting a dynamic, two-phase culture environment. Neither mock-transduced constructs in the RSB culture nor the Bac-CB-transduced constructs in the static culture grew into uniform cartilaginous tissues. Only the Bac-CB-transduced constructs cultured in the RSB for 3 weeks resulted in cartilaginous tissues with hyaline appearance, uniform cell distribution, cartilage-specific gene expression and considerably enhanced cartilage-specific extracellular matrix deposition, as determined by histological staining, reverse transcription-PCR analyses and biochemical assays. This is the first study demonstrating that combination of baculovirus-mediated growth factor expression and RSB culture synergistically enhanced in vitro creation of cartilaginous tissues from dedifferentiated chondrocytes. Since baculovirus transduction is generally considered safe, this approach represents a viable alternative to stimulate the formation of engineered cartilage in a more cost-effective way than the growth factor supplementation.

Environmental exposure to lead and progressive diabetic nephropathy in patients with type II diabetes.

Studies indicate that environmental exposure to lead is associated with reduced renal function. Whether lead affects progressive diabetic nephropathy is unclear. Eighty-seven patients with type II diabetes and diabetic nephropathy (serum creatinine of 1.5-3.9 mg/dl) with normal body lead burden and no lead exposure history were observed over a 12-month period. Thirty subjects with high normal body lead burdens (80-600 microg) were randomly assigned to a chelation and control group. For 3 months, the 15 chelation-group patients underwent lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly until body lead burden fell <60 microg, and the 15 control group subjects received a weekly placebo. During the following 12 months, renal function was regularly assessed at 3-month intervals. The primary outcome was an elevation of serum creatinine to 1.5 times baseline value during the observation period. A secondary outcome was temporal changes in renal function following chelation therapy. Twenty-six patients achieved the primary outcome. Basal blood lead levels and body lead burden were the most important risk factors in predicting progressive diabetic nephropathy. Following chelation, the rates of decline in glomerular filtration rates in the chelation group and the control group, respectively, were 5.0+/-5.7 ml and 11.8+/-7.0 ml/min/year/1.73 m(2) of body surface area (P=0.0084) during follow-up, although both groups had similar rates of progression of renal function during the 12-month observation period. We concluded that low-level environmental lead exposure accelerates progressive diabetic nephropathy and lead-chelation therapy can decrease its rate of progression.

Aristolochic acid-related nephropathy associated with the popular Chinese herb Xi Xin.

Chinese herbs nephropathy is known as a subacute interstitial nephritis attributed to aristolochic acid. This work describes the case of a 49-year-old male who displayed subacute renal failure induced by ingestion of herbal powder containing Xi Xin, which includes aristolochic acid. Since Xi Xin is a common ingredient in traditional formulae, care needs to be taken in the future to identify the aristolochic acid concentration of different components of Xi Xin. Xi Xin containing aristolochic acid should be forbidden for use in remedies in order to prevent the harmful effects of aristolochic acid.

Coordination polymers based on cobridging of rigid and flexible spacer ligands: syntheses, crystal structures, and magnetic properties of [Mn(bpy)(H2O)(C4H4O4)].0.5bpy, Mn(bpy)(C5H6O4), and Mn(bpy)(C6H8O4).

Reactions of 4,4'-bipyridine (bpy) with Mn(C(4)H(4)O(4)).4H(2)O and Mn(C(5)H(6)O(4)).4H(2)O in methanolic aqueous solutions yielded [Mn(bpy)(H(2)O)(C(4)H(4)O(4))].0.5bpy (1) and Mn(bpy)(C(5)H(6)O(4)) (2), respectively, and reactions of freshly prepared Mn(OH)(2)(-)(2)(x)(CO(3))(x).yH(2)O, adipic acid and 4,4'-bipyridine in a methanolic aqueous solution afforded Mn(bpy)(C(6)H(8)O(4)) (3). The six-coordinate Mn atoms in 1 are interlinked by flexible succinato ligands to form layers, which are sustained by rigid bpy ligands into an 3D open framework with the free bpy molecules in tunnels. The ribbonlike chains in 2 result from Mn atoms bridged by glutarato ligands and are connected by bpy ligands into open layers. In 3, the Mn atoms are bridged by both bpy and adipato ligands to form 3D nanoporous frameworks and 2-fold interpenetration of the resulting 3D frameworks completes the crystal structure. In comparison with 1 and 2, compound 3 displays significant antiferromagnetic behavior at low temperature. The antiferromagnetic exchange becomes stronger from 1 through 2 to 3, and the antiferromagnetic ordering of Mn(2+) centers is related to the syn-syn bridging mode of the terminal carboxylate groups of alpha,omega-dicarboxylate anions. Crystal data: C(19)H(18)MnN(3)O(5) (1), monoclinic P2(1)/c, a= 11.686(2) A, b = 17.847(2) A, c = 8.852(1) A, beta = 99.67(1) degrees, V = 1819.9(4) A(3), Z = 4, D(c) = 1.545 g.cm(-3); C(15)H(14)MnN(2)O(4) (2), triclinic P, a = 8.145(2) A, b = 9.574(2) A, c = 10.180(1) A, alpha = 108.01(3) degrees, beta = 93.55(3) degrees, gamma = 105.30(1) degrees, V = 719.2(2) A(3), Z = 2, D(c) = 1.576 g.cm(-3); C(15)H(14)MnN(2)O(4) (3), triclinic P, a = 8.544(1) A, b= 8.881(1) A, c = 10.949(2) A, alpha = 108.81(1) degrees, beta = 95.40(1) degrees, gamma = 101.94(1) degrees, V = 757.7(2) A(3), Z = 2, D(c) = 1.557 g.cm(-3).

Fractional band filling in an atomic chain structure.

A new chain structure of Au is found on stepped Si(111) which exhibits a 1/4-filled band and a pair of > or =1/2-filled bands with a combined filling of 4/3. Band dispersions and Fermi surfaces for Si(553)-Au are obtained by photoemission and compared to that of Si(557)-Au. The dimensionality of both systems is determined using a tight binding fit. The fractional band filling makes it possible to preserve metallicity in the presence of strong correlations.