This review gives a brief presentation of the theory of UAE, disc

This review gives a brief presentation of the theory of UAE, discusses recent advances that influence its efficiency, and summarizes the main results in selected applications published in the period 2010-12. There is discussion of the advantages and the disadvantages of UAE and the possibility of coupling UAE with other analytical techniques. (C) 2012 Elsevier Ltd. All rights reserved.”
“At least 50-60% of oocytes derived from IVF procedures are chromosomally abnormal due to meiotic I or II errors. Through the use of polar body and blastomere diagnosis, euploid embryos Suitable for transfer can be identified. Those embryos that are Akt inhibitor aneuploid are usually discarded,

or otherwise can be used to generate chromosomally abnormal human embryonic stem cell (hESC) lines. The authors’ centre has one of

the largest repositories of hESC lilies with genetic and chromosomal disorders GANT61 datasheet generated from preimplantation genetic diagnosis (PGD) abnormal embryos. The results, studying hESC lilies derived from PGD abnormal zygotes, imply that aneuploidies resulting from meiotic non-disjunction have a greater impact on viability of cells of the human embryos than those originating from post-zygotic mitotic non-disjunction.”
“We report the case of a 37-year-old male with Cowden disease that caused a gradual neurological deficit because of rupture of a brain stem cavernous hemangioma. Removal of the hemangioma and hematoma was performed with an infrafacial triangle approach. Nine months after the operation, magnetic resonance imaging showed abnormal vessels on the cerebellar surface. Digital subtraction angiography showed a dural arteriovenous fistula (dAVF)

from part of the meningeal artery to the ectatic inferior vermian vein with cortical reflux. After embolization, surgical obliteration BMS-345541 manufacturer of the dAVF was performed. Surgical findings showed neovascularization in the thickened dura, in which dural vessels shunted to cerebellar vessels through adhesion between the dura mater and cerebellar surface. Therefore, the thickened dura was removed with the cerebellar surface. This case suggests that postoperative angiogenesis may cause arteriovenous fistula in patients with Cowden disease.”
“Purpose: To study the effect of process conditions on the size of gold nanoparticles (AuNPs) prepared by chemometric technique.

Methods: AuNPs were prepared by adding 5 ml of 5 mM of gold (III) chloride hydrate HAuCl4 (2 mg/mL) to 85 ml of filtered deionized water, then refluxed in a 250 mL flask over a hot plate and heated to boiling point. Five milliliters of sodium citrate solution of varying concentrations were quickly added to the boiling solution and stirred for 30 min until the color turned to wine red.

The article also discusses special considerations regarding sampl

The article also discusses special considerations regarding sampling, sample size and data interpretation when including such information in a TB prevalence survey.”
“Although considerable progress has been made in developing models of cerebellar

function in sensorimotor control, the exact nature of the basic operations performed by the cerebellum remain elusive. Several major theories have emerged these last decades. According to the hypothesis of Marr and Albus, the climbing fiber input carries an error signal weakening the strength of a subset of parallel fibers/Purkinje neurons synapses in the cerebellar cortex. Cerebellar circuits would gain the control of movement through trial and error. The hypothesis of internal models emulating movements is currently highly cited. There is a general agreement that (1) the central nervous system has to cope with an intrinsic time delay of sensory feedback related to motor Fedratinib inhibitor activities and (2) estimations of future motor states are essential to perform fast and accurate JNK-IN-8 research buy movements. According to this second theory, cerebellar dysmetria,

one of the cardinal cerebellar deficits, would result from a distorted predictive control. A third popular theory relates to the inverse models that would be stored in the cerebellum. Acquisition of a motor act would require forward models, and the acquisition process itself would generate an inverse model to allow an unconscious coordinated movement. Recently, an international panel of experts from various disciplines discussed the prevailing opinions in a consensus statement and tried to extract their clinical relevance in terms of pathogenesis of the clinical symptoms. Although a consensus is still not reached, the prevailing opinions provide a sound GSK J4 purchase framework to conduct novel studies and try to discover the secrets of cerebellar circuits.”
“Inconsistent results with

regard to adiponectin levels in patients with colorectal cancer (CRC) and adenoma have been reported. To evaluate adiponectin levels in patients with CRC and adenoma, a meta-analysis on studies which compared adiponectin levels in patients with CRC or adenoma with healthy controls was carried out. A literature search was performed through Pubmed, EMBASE, and Science Citation Index Expanded database. Pooled-weighted mean differences and 95% confidence intervals (95%CI) were calculated by using random-effects models. Heterogeneity between studies was assessed using the Cochran’s Q and I-2 statistics. A total of 13 studies were identified, which included 2632 cases of CRC or adenoma and 2753 healthy controls. Adiponectin levels were significantly lower in patients with CRC or adenoma compared with healthy controls, with significant heterogeneity [weighted mean differences of -1.51 (95% CI: -2.42 to -0.59; P-heterogeneity < 0.

On the other hand, AMP is only one of several measures to prevent

On the other hand, AMP is only one of several measures to prevent perioperative infectious complications. It is necessary to know that the patient must have no bacteriuria and that preoperative hair removal should be avoided.”
“Background: It is generally accepted that prosthetic elbow replacement should be avoided in young patients because of an anticipated

high rate of early failure. The purpose of this paper was to define the success, prosthetic survival rate, and problems encountered in patients who were treated with a semiconstrained total elbow arthroplasty when they were forty years of age or less.

Methods: We retrospectively reviewed the records of 758 patients who had undergone primary arthroplasty with the Coonrad-Morrey total elbow prosthesis for any reason between 1982 and 2003. We Quisinostat order identified fifty-five total elbow arthroplasties that had been performed in forty-nine patients (thirty-eight women and eleven men) who were forty years of age or less (mean, thirty-three years) at the time of the

operation and that had been followed for a minimum of five years. Six patients had a bilateral procedure. The indication for the arthroplasty was inflammatory SN-38 arthritis in thirty patients and posttraumatic arthritis in nineteen. Patients with hemophilia or a neoplasm were excluded. The medical record data were used to calculate the preoperative and postoperative Mayo Elbow Performance Score.

Results: The mean duration of follow-up was ninety-one months. During this period, twelve (22%) of the elbows had undergone a subsequent surgical procedure: four because of loosening, three because of triceps weakness, three because of wear, and two because of deep infection. On the basis of the Mayo Elbow Performance Score at the last review, thirty-six results

(65%) were considered to be excellent; fifteen (27%), good; three (5%), fair; and one (2%), poor.

Conclusions: Semiconstrained total elbow arthroplasty in young patients was associated with a 22% revision rate at a mean of ninety-one months, selleck chemicals llc and the rate of revision was significantly higher for patients with posttraumatic arthritis. Despite this revision rate, fifty-one elbows (93%) had a good or excellent Mayo Elbow Performance Score.”
“Purpose of review

We discuss pathology-based characterization and classification of acquired immune and inflammatory myopathies (IIMs).

Recent findings

Several types of IIMs do not fit well into the typical IIM subclassifications: dermatomyositis, polymyositis and inclusion body myositis (IBM). Myopathologic features that can provide additional diagnostic clarification in IIM are types of muscle fiber pathology; immune changes (cellular and humoral); and tissues with distinctive involvement (connective tissue, vessels and muscle fibers).

Results: 280 patients with a median age of 69 years were included

Results: 280 patients with a median age of 69 years were included (99 UUT-UC treated via nephroureterectomy and 181 B-UC treated via radical cystectomy).

Median follow-up was 29 months. None received neoadjuvant https://www.selleckchem.com/products/SB-525334.html chemotherapy. Patients with UUT-UC presented less commonly with invasive disease compared to those with B-UC (44 vs. 77% were >pT2). Overall, 5-year OS for the B-UC group was significantly lower than for the UUT-UC group (60.8 vs. 74.5%, p = 0.02). However, when patients were stratified by stage (>pT2), patients with B-UC had similar OS compared to those with UUT-UC (54.6 vs. 60.8%, p = 0.74). Conclusion: Invasive UUT-UC appears to have similar tumor biology compared to B-UC. Whether we can safely extrapolate on the benefit of neoadjuvant

and adjuvant strategies to patients with UUT-UC requires further investigation. Copyright (C) 2010 S. Karger AG, Basel”
“Thromboangiitis obliterans (TAO), or Buerger disease, is a segmental Occlusive inflammatory disorder of the arteries and veins, and etiopathogenesis is still obscure. It is strongly connected to the use of tobacco products, especially smoking. Smoking cessation is obligatory for Success VX-770 research buy of the medical treatment. In the Current Study, we investigated the prevalence of endothelial nitric oxide synthase (eNOS) 894 G -> T and endothelin-1 (ET-1) 8000 T -> C polymorphisms in association with TAO to reveal any possible involvement in the TAO pathophysiology. The T allele of the eNOS 894 G -> T polymorphism was found to be associated with the prevention of TAO.”
“Purpose: With the increasing use of radiation as adjuvant therapy in breast cancer, the effects of g

radiation on the selleck chemicals remaining normal breast are of increasing importance. The complexities of multiple cellular types within breast tissues and the role of the pleiotropic Tumour Protein 53 (TP53, p53) protein with its downstream transcriptional targets and cellular processes may be central to the effects on residual normal breast tissues.

Conclusion: While a detailed understanding of p53 protein-mediated responses in normal breast tissues remains elusive, p53 appears to have a pivotal role in the effects of g radiation on normal breast epithelium, but not stromal cells, which may account for the differing clinical effects of g radiation in women treated for breast cancer.”
“This article reports a female who presented with bleeding, acquired factor VIII and von Willebrand factor (aFVIII-VWF) deficiency, and central deficiency in the thyroid and adrenal axis (Sheehan’s syndrome). After starting hormone replacement therapy, relief of bleeding in manifestations was associated with correction of both FVIII and VWF to normal. This report draws attention to a rare association between the acquired form of von Willebrand disease and hypothyroidism of central origin.

13 to 7 25 mu m This effect was attributed to an appreciable red

13 to 7.25 mu m. This effect was attributed to an appreciable reduction in droplet charge when the pH was reduced (zeta

approximate to -35 mV at pH 3 and -2 mV at pH 3) thereby decreasing the electrostatic repulsion between droplets. It was proposed that the negative charge on the SMP-coated droplets was due to the presence of anionic substances within the droplets, such as palmitic acid (pK(a)approximate to 4.9). Palmitic acid may have been an impurity in the original ingredient or it may have been generated due to degradation of SMP during storage. The addition of anionic lyso-lecithin markedly improved the stability of the emulsions to droplet aggregation and phase separation at low pH, which was attributed to an increased electrostatic repulsion between the droplets. This study has important consequences for Selleck Lonafarnib the formulation of acidic beverage emulsions with improved stability and physicochemical performance. (C) 2011 Elsevier Ltd. All rights reserved.”
“Chronic lung infection by mucoid Pseudomonas aeruginosa is one of the major pathologic features in patients with cystic fibrosis. Mucoid P. aeruginosa is notorious for its biofilm forming capability and resistance to immune attacks. In this study, the roles of extracellular polymeric substances from biofilms formed by mucoid P.

aeruginosa were investigated. Alginate is not an essential structure component for mucoid P. aeruginosa biofilms. selleckchem Genetic studies revealed that Pel and Psl polysaccharides serve as YM155 research buy essential scaffold and mediate macrocolony formation in mucoid P. aeruginosa biofilms. The Psl polysaccharide is more important than Pel polysaccharide in mucoid P. aeruginosa biofilm structure maintenance and phagocytosis resistance. The polysaccharides were further found to protect mucoid P. aeruginosa strain from host immune clearance in a mouse model of acute lung infection.”
“The muscle sarcoplasmic proteins from bovine M. longissimus thoracis muscle were studied using

proteomics to identify possible protein markers for meat tenderness. This study included 3 experiments: A1, A2, and B. From a collection of biopsies from the bovine M. longissimus thoracis muscle, excised 4 d before slaughter from 178 Norwegian Red young bulls, 26 biopsies were studied in Exp. A1. Based on Warner-Bratzler shear force (WBSF) values at 7 d postmortem, the biopsies were separated into a tender and a tough group of 13 bulls each and analyzed by 2-dimensional gel electrophoresis (2-DE) and Western blotting. The 2-DE experiments identified 4 different proteins: stress-70 protein, protein DJ-1, peroxiredoxin-6, and malate dehydrogenase, which were different in abundance in the tender and tough groups. However, only peroxiredoxin-6 was confirmed by quantification from Western blots. Peroxiredoxin-6 is an antioxidant enzyme that plays a role in protecting cells from oxidative stress.

Functional coupling of LEC1/L1L-[AtNF-YC2] and bZIP67 was also ob

Functional coupling of LEC1/L1L-[AtNF-YC2] and bZIP67 was also observed in the regulation of sucrose synthase 2 (SUS2). Immunoprecipitation experiments revealed that L1L and bZIP67 formed a protein complex in vivo. These results

demonstrate a novel plant-specific mechanism for NF-Y subunit function that enables LEC1 and L1L to regulate a defined developmental network.”
“SETTING: The country of Georgia has a high burden of multi- (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB).

OBJECTIVE: To assess the performance of the Geno-Type (R) MTBDRsl assay in the detection of resistance to kanamycin (KM), capreomycin (CPM) and ofloxacin (OFX), and of XDR-TB.

DESIGN: Consecutive acid-fast bacilli smear-positive sputum specimens identified as MDR-TB using the MTBDRplus test were evaluated with the MTBDRsl assay and conventional second-line drug susceptibility testing (DST).

RESULTS: Among 159 specimens, amplification was adequate Selleckchem MAPK inhibitor in 154 (97%), including 9 of 9 culture-negative and 2 of 3 contaminated specimens. Second-line DST selleck chemicals llc revealed that 17 (12%) Mycobacterium tuberculosis isolates were XDR-TB. Compared to DST, the MTBDRsl had 41% sensitivity and 98% specificity in detecting XDR-TB

and 81% sensitivity and 99% specificity in detecting OFX resistance. Sensitivity was low in detecting resistance to KM (29%) and CPM (57%), while specificity was ON-01910 mouse respectively 99% and 94%. Median times from sputum collection to second-line DST and MTBDRsl results were 70-104 vs. 10 days.

CONCLUSION: Although the MTBDRsl assay had a rapid turnaround time, detection of second-line drug resistance was poor compared

to DST. Further genetic mutations associated with resistance to second-line drugs should be included in the assay to improve test performance and clinical utility.”
“A sensitive, isocratic reversed-phase high performance liquid chromatographic method involving fluorescence detection was developed for the determination of donepezil hydrochloride in tablets and in human plasma. Pindolol was used as an internal standard. Good chromatographic separation was achieved by using an analytical column C18. The system operated at room temperature using a mobile phase consisting of methanol, phosphate buffer (0.02 mol L(-1)) and triethyl amine (pH 3.5) (55 : 45 : 0.5, V/V/V) at a flow rate 0.9 mL(-1) min. The analyte and internal standard were extracted from human plasma via liquid-liquid extraction. The proposed method was validated for sensitivity, selectivity, linearity, accuracy and precision. The calibration curve was linear over the range of 5-2000 ng mL(-1) of donepezil with detection limit of 1.5 ng mL(-1). Intra-and inter-day relative standard deviations were less than 2.5 %. The method was found to be suitable for quality control of donepezil hydrochloride in bulk drug as well as in human plasma.

Consequently, transient epileptic amnesia may be readily misdiagn

Consequently, transient epileptic amnesia may be readily misdiagnosed as a nonepileptic memory dysfunction in older individuals. When appropriately recognized, it has

been described as a treatment-responsive syndrome amenable to antiepileptic drugs. We describe a patient with drug-resistant transient epileptic amnesia treated with unilateral temporal lobectomy. Prolonged postictal slowing in the mesial temporal structures was evident on invasive electroencephalography 5 hours after the occurrence of a brief focal seizure. These findings support the theory of a Todd phenomenon as the underlying pathophysiological mechanism in transient epileptic amnesia. (C) 2010 Elsevier Inc. All rights reserved.”
“Bulgaria BMN 673 DNA Damage inhibitor had been free from brucellosis since 1958, Liproxstatin-1 manufacturer but during 2005-2007, a reemergence of human and animal disease was recorded. The reemergence of this zoonosis in the country highlights the importance of maintaining an active surveillance system for infectious diseases that will require full cooperation between public health and veterinary authorities.”
“Study Design. Cross sectional.

Objective. This study presents the factor analysis of the Spinal Appearance Questionnaire (SAQ) and its psychometric

properties.

Summary of Background Data. Although the SAQ has been administered to a large sample of patients with adolescent idiopathic scoliosis (AIS) treated surgically, its psychometric properties have not been fully evaluated. This study presents the factor analysis and scoring of the SAQ and evaluates its psychometric properties.

Methods. The SAQ and the Scoliosis Research

Society-22 (SRS-22) were administered to AIS patients who were being observed, braced or scheduled for surgery. Standard demographic data and radiographic measures including Lenke type and curve magnitude were also collected.

Results. Of the 1802 patients, 83% were female; with a mean age of 14.8 years and mean initial Cobb angle of 55.degrees (range, 0 degrees 123 degrees). From the 32 items of the SAQ, 15 loaded on two factors Selonsertib clinical trial with consistent and significant correlations across all Lenke types. There is an Appearance (items 1-10) and an Expectations factor (items 12-15). Responses are summed giving a range of 5 to 50 for the Appearance domain and 5 to 20 for the Expectations domain. The Cronbach’s alpha was 0.88 for both domains and Total score with a test-retest reliability of 0.81 for Appearance and 0.91 for Expectations. Correlations with major curve magnitude were higher for the SAQ Appearance and SAQ Total scores compared to correlations between the SRS Appearance and SRS Total scores. The SAQ and SRS-22 Scores were statistically significantly different in patients who were scheduled for surgery compared to those who were observed or braced.

Conclusion.

aureus The oxacillin MIC was 16 mu g/mL and the mecA gene and SC

aureus. The oxacillin MIC was 16 mu g/mL and the mecA gene and SCCmec type V were determined by PCR. Although treatment had been appropriated, the patient died after rapid progressive respiratory failure and another nosocomial sepsis. It is important not only to identify

S. lugdunensis in view of its clinical course, but also to determine Crenolanib price its susceptibility to oxacillin by detecting the mecA gene or its product.”
“Background: Left ventricular (LV) wall stiffening plays an important role in the development of heart failure with preserved ejection fraction (HFpEF). Based on the linear elastic theory, we hypothesized that the evaluation of epicardial movement during diastole is helpful for the noninvasive assessment of LV wall distensibility.

Methods and Results: Based on the linear elastic theory, the epicardial movement Selleck Mizoribine index (EMT) was calculated on the echocardiograin as:

endocardial movement during diastole – epicardial movement

during diastole / LV posterior wall thickness at end-systole

We calculated diastolic wall strain (DWS) as follows to examine whether DWS substitutes for EMI:

LV posterior wall thickness at end-systole – LV posterior wall thickness at end-diastole / LV posterior wall thickness at end-systole

The animal study using hypertensive Dahl salt-sensitive rats, HFpEF model, and normotensive Dahl rats showed the significant and inverse correlation of EMI or DWS with myocardial stiffness constant. Preload alteration did not affect EMT or DWS. In the clinical study, the HFpEF patients had lower EMT and DWS than the normal volunteers and the asymptomatic patients with LV hypertrophy.

Conclusions: The evaluation of epicardial movement may be useful in noninvasively assessing wall distensibility in the absence of LV systolic dysfunction. (J Cardiac

Fail 2009;15:68-77)”
“It is well known that propolis has the ability to prevent hyperglycemia. However, the underlying mechanism is not yet fully understood. We therefore investigated whether a Brazilian propolis ethanol extract affects glucose uptake and translocation of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle cells. In L6 myotubes, the extract at 1 g/mL significantly promoted GLUT4 translocation and glucose uptake activity. Regarding the mechanism of selleck GLUT4 translocation, propolis extract induced both PI3K and AMPK phosphorylation in a dose-dependent manner in L6 myotubes. However, we could not define which pathway was preferentially associated with GLUT4 translocation, because both PI3K and AMPK inhibitors revealed off-target effects to each other. The main polyphenols found in the propolis extract, artepillin C, coumaric acid, and kaempferide, promoted GLUT4 translocation in L6 myotubes. Additionally, these compounds activated both PI3K- and AMPK-dependent dual-signaling pathways. However, only kaempferide increased glucose uptake activity under our experimental conditions.

Hence, the melatonergic modulation by agomelatine is suggested as

Hence, the melatonergic modulation by agomelatine is suggested as one of the mechanisms for

its antidepressant effect. Agomelatine’s action on dendritic neurogenesis in animal models of depression is also identified as yet another action. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:290-308)”
“Purpose: The study aimed to systematically review the effect of low-molecular-weight heparin (LMWH) thromboprophylaxis in medical-surgical critically ill patients in the intensive care unit.

Methods: In duplicate and independently, click here we searched for relevant articles using MEDLINE and EMBASE; we also contacted experts and reviewed reference lists. For included studies, we abstracted data on study and patient characteristics, LMWH use, clinical outcomes (venous thromboembolism [VTE], bleeding, and mortality), laboratory outcomes (anti-Xa

levels and thrombocytopenia), and methodological BI 2536 supplier quality.

Results: We included 8 prospective cohort studies and 1 randomized trial, with a total of 629 patients. Eight studies (n = 406 patients) reported anti-Xa levels and only 3 studies (n = 240 patients) reported on at least one clinical outcome. Low-molecular-weight heparin does not appear to bioaccumulate based on repeated measurements of trough anti-Xa levels. Thrombocytopenia occurred in 9.3% of patients receiving

LMWH; heparin-induced thrombocytopenia was not reported. In studies reporting clinical Outcomes, the frequency of VTE in patients receiving LMWH ranged from 5.1% to 15.5%, bleeding complications ranged from 7.2% to 23.1%, and mortality ranged from 1.4% to 7.4%.

Conclusions: Low-molecular-weight heparin may be effective for thromboprophylaxis in medical-surgical critically ill patients, but no trials have compared LMWH against an alternative active strategy; thus, LMWH cannot be recommended routinely. Trials testing LMWH thromboprophylaxis are required, which examine patient-important R788 end points such as the incidence and clinical consequences of VTE, bleeding, heparin-induced thrombocytopenia, and mortality. (C) 2009 Elsevier Inc. All rights reserved.”
“Deep luminescence centers in Si associated with transition metals have been studied for decades, both as markers for these deleterious contaminants, as well as for the possibility of efficient Si-based light emission. They are among the most ubiquitous luminescence centers observed in Si, and have served as testbeds for elucidating the physics of isoelectronic bound excitons, and for testing ab-initio calculations of defect properties.

The chloroderivative of the diacid (I) was synthesized by its rea

The chloroderivative of the diacid (I) was synthesized by its reaction with thionyl chloride, this was followed by condensation with different diamines with phenyl, naphthyl, ether, sulfide, and cardo groups to generate a series of diamidediimidediamines (DADIDAs). The resultant DADIDAs were characterized by elemental analysis and spectroscopic techniques, namely, CYT387 molecular weight Fourier transform infrared

spectroscopy and NMR spectroscopy, and were used as epoxy curing agents to impart flame retardancy to the epoxy system. Two epoxy blends (designated as ES and EP) were prepared by the homogeneous mixing of diglycidyl ether of bisphenol A (DGEBA) with 1,3-bis(3-glycidyloxypropyl)tetramethyl disiloxane and DGEBA with tris(glycidyloxy)phosphine

oxide: each in a ratio of 3 : 2 respectively. The synergistic effect of phosphorus/silicon with nitrogen on the thermal properties of the modified epoxy system was studied. The curing behavior of the epoxy resins formulated by the reaction of stoichiometric HDAC inhibitor amounts of ES/EP with the synthesized DADIDAs were determined by differential scanning calorimetry, and the thermal stabilities of the cured epoxies were evaluated by thermogravimetric analyses (TGAs) under nitrogen and air. TGA indicated that the residual weight percentage of polymers at 800 degrees C was in the range 36.460.0 in nitrogen, and in air, it was up to 6.5. However, the major loss

in weight in air occurred at elevated temperature; this demonstrated their potential use as flame-retardant epoxy systems for electronic/electrical encapsulants. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012″
“Crucial questions in the debate on the origin of quintessential human behaviours are whether modern cognition and associated innovations are unique to our species and whether they emerged abruptly, gradually or as the result of a discontinuous process. Three scenarios have been proposed to account for the origin of cultural modernity. The first argues that modern cognition is unique to our species and the consequence of a genetic mutation that took place approximately 50 ka in Africa among already Bromosporine cost evolved anatomically modern humans. The second posits that cultural modernity emerged gradually in Africa starting at least 200 ka in concert with the origin of our species on that continent. The third states that innovations indicative of modern cognition are not restricted to our species and appear and disappear in Africa and Eurasia between 200 and 40 ka before becoming fully consolidated. We evaluate these scenarios in the light of new evidence from Africa, Asia and Europe and explore the mechanisms that may have led to modern cultures.