Nonadiabatic Derivative Couplings through Multiple Franck-Condon Modes Dictate the Energy Gap Law for Near and Short-Wave Infrared Dye Molecules.

Near infrared (NIR, 700-1000 nm) and short-wave infrared (SWIR, 1000-2000 nm) dye molecules exhibit significant nonradiative decay rates from the first singlet excited state to the ground state. While these trends can be empirically explained by a simple energy gap law, detailed mechanisms of nearly universal behavior have remained unsettled for many cases. Theoretical and experimental results for two representative NIR/SWIR dye molecules reported here clarify the key mechanism for the observed energy gap law behavior. It is shown that the first derivative nonadiabatic coupling terms serve as major coupling pathways for nonadiabatic decay processes from the first excited singlet state to the ground state for these NIR and SWIR dye molecules and that vibrational modes other than the highest frequency modes also make significant contributions to the rate. This assessment is corroborated by further theoretical comparison with possible alternative mechanisms of intersystem crossing to triplet states and also by comparison with experimental data for deuterated molecules.

Detection of Crimean-Congo hemorrhagic fever virus in blood-fed Hyalomma ticks collected from Mauritanian livestock.

BACKGROUND: Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Orthonairovirus (Nairovididae) and is a (re)emerging tick-borne pathogen. It is endemic in most parts of Africa, Asia and southern Europe, and can cause severe hemorrhagic symptoms in humans, with high fatality rates (5-30%). METHODS: Hyalomma ticks were collected from four different livestock herds (cattle and camels) in Mauritania in 2018. The tick species were determined morphologically and confirmed molecularly by using the cytochrome oxidase 1 gene marker. For the detection of CCHFV, ticks were tested individually by one-step multiplex real-time reverse-transcriptase quantitative polymerase chain reaction. The small segment of all positive samples was sequenced to determine the CCHFV genotype. RESULTS: In total, 39 of the 1523 ticks (2.56%) collected from 63 cattles and 28 camels tested positive for CCHFV. Three Hyalomma species were identified. Hyalomma rufipes had the largest proportion of positivity (5.67%; 16/282), followed by Hyalomma dromedarii (1.89%; 23/1214). No Hyalomma impeltatum tested positive (0%; 0/21). Positive ticks were found in only six out of 91 host animals. Viral sequence analysis revealed the presence of two different CCHFV lineages (Africa I and Africa III). CONCLUSIONS: In this study, 2.56% of Hyalomma ticks collected from camels and cattle in Mauritania tested positive for CCHFV. However, the true prevalence of CCHFV in unfed ticks may be lower, as a considerable number of ticks may have been passively infected during blood-feeding by co-feeding ticks or due to viremia of the host. The results indicate the need to track the actual area of circulation of this virus.

Maternal admissions to intensive care units in France: Trends in rates, causes and severity from 2010 to 2014.

INTRODUCTION: Maternal intensive care unit admission is an indicator of severe maternal morbidity. The objective of this study was to estimate rates of maternal intensive care unit admission during or following pregnancy in France, and to describe the characteristics of women concerned, the severity of their condition, associated diagnoses, regional disparities, and temporal trends between 2010 and 2014. METHODS: Women hospitalised in France in intensive care units during pregnancy or up to 42 days after pregnancy between January 2010 and December 2014 were identified using the national hospital discharge database (PMSI-MCO). Trends in incidence rates were quantified using percentages of average annual variation based on a Poisson regression model. RESULTS: In total, 16,011 women were admitted to intensive care units, representing an overall incidence of 3.97‰ deliveries. This number decreased significantly by 1.7% on average per year. For women who gave birth (60.5% by C-section), 62.5% of admissions occurred during their hospitalisation for delivery. The SAPS II score, an indicator of severity, significantly increased from 18.4 in 2010 to 21.5 in 2014. Obstetrical haemorrhage (39.8%) and hypertensive complications during pregnancy (24.8%) were the most common reasons for admission. In mainland France, the Ile-de-France (i.e., greater Paris) region had the highest rates of intensive care units admission (5.05‰) while the Pays-de-la-Loire region had the lowest (2.69‰). CONCLUSION: The rate of maternal intensive care unit admission decreased from 2010 to 2014 in France, with a concomitant increase in case severity. In-depth studies are needed to understand the territorial disparities identified.

[Perinatal health and medical administrative data: What uses, which stakeholders, what the issues for birth data? - Special REDSIAM]. / Périnatalité et bases de données médico-administratives : quels usages, quels acteurs, quels enjeux pour les données sur les naissances ? ­ Spécial REDSIAM.

BACKGROUND: The uses of medical administrative data (MAD/BDMA) emerged in perinatal health following the work on regionalization of very pre-term birth. They have become more numerous since the late 2000s. The objective of this article is to take stock of the existing work carried out within the REDSIAM-perinatality group, on MAD/BDMA and their uses for the period of "birth". METHODS: The studied MADs are the Hospital Discharge Data (PMSI) and the French national health database (SNIIRAM). The material includes knowledge shared by the members of the REDSIAM-perinatality group, scientific references and gray literature. RESULTS: Our exploratory study shows that the uses of MAD in perinatal health are diversified at the local, regional and national levels. The works and publications, increasing, take the form of public access of processed data. Collective thinking makes it possible to move from a localized use to an institution, a network or several, to a national use and an inscription in public authorities' responses. In 2015/2016, two institutional sites provide access to data on maternal and child health: Data.Drees and ATIH ScanSanté. MAD/BDMA uses are multiple: epidemiological use (count of births by gestational age, weight in particular; perinatal indicators), quality of care, planning (maternity activities, regionalization of care). There is an increasing interest among stakeholders, producers and/or operators of MAD/BDMA (decision-makers, professionals or researchers). CONCLUSION: The BDMA, including the PMSI and the SNIIRAM, are used and relevant in Perinatal health with the rise of health networks, the territorialisation of health, in an increased demand for quality of care. Their use will increase the reliability of the data collected and an inscription in the validation studies, more and more numerous in the field of BDMA. The algorithms need to be more finely compiled, validated and enhanced.

Species Identification and Resistance Status of Anopheles gambiae s.l. (Diptera: Culicidae) Mosquitoes in Guinea.

Insecticide resistance is one of the primary threats to the recent gains in malaria control. This is especially true in Guinea, where long-lasting insecticidal nets are currently the primary vector control intervention. To better inform the national malaria control program on the current status of insecticide resistance in Guinea, resistance bioassays were conducted, using Anopheles gambiae s.l. Giles, in three sites. Molecular analyses were also done on An. gambiae s.l. to determine the species and find whether the target-site mutations kdr and Ace1R were present. Susceptibility tests revealed resistance to DDT and pyrethroids, although mosquitoes were susceptible to deltamethrin in two of the three sites tested. Mosquitoes were susceptible to bendiocarb, except in Kissidougou, Guinea. The kdr-west mutation was widespread and the frequency was 60% or more in all sites. However, the Ace1R mutation was present in low levels. Insecticide susceptibility should continue to be monitored in Guinea to ensure insecticide-based vector control methods remain effective.

Preliminary results of CO2 laser-assisted sclerectomy surgery (CLASS) in the treatment of advanced glaucoma in a Chinese population.

To evaluate the efficacy and safety of CO2 laser-assisted sclerectomy surgery (CLASS) in Chinese patients with advanced glaucoma.Patients with advanced glaucoma who were candidates for glaucoma filtration surgery were included. The intraocular pressure (IOP) and number of antiglaucoma medications were documented before surgery and at all postoperative clinic visits. All intra- and postoperative complications were documented. The primary outcome measures were the changes in IOP and medication use before and after the procedure as well as complications from the procedure. The secondary outcome measure included the CLASS success rate.Twenty patients (23 eyes) underwent CLASS between November 2014 and September 2015. Nineteen eyes had primary open-angle glaucoma, 2 eyes had primary angle-closure glaucoma, and 2 eyes had uveitic glaucoma. One patient was lost to follow-up. The mean age of subjects was 68.1 ±â€Š11.9 years. IOP was significantly reduced at 1 day and 1 week after CLASS. At 6 months, the IOP and number of medications were significantly reduced by 19.0% and 38.2%, respectively (both P < 0.0001). One patient had intraoperative trabeculo-Descemet membrane perforation. Two patients required laser goniopuncture and 2 required needling between 3 and 6 months postoperatively. The overall success rate was 81.8% at 6 months.CLASS achieved a modest IOP reduction in the early postoperative period and was overall a safe procedure for advanced glaucoma.

Patient-appropriate health literacy educational materials in ophthalmology.

OBJECTIVE: To evaluate the literacy level of patients with glaucoma in a tertiary care teaching centre compared with a rural community centre and to assess comprehension of and preference for educational material written at different reading levels. DESIGN: Prospective, randomized, double-blinded study. PARTICIPANTS: Patients with glaucoma presenting for routine examination or referral at a tertiary care academic centre in southwestern Ontario and a single general ophthalmology clinic located in a moderately sized suburban community in Ontario, Canada, were invited to participate in this study. Patients aged 19 to 90 with sufficient visual acuity to read the pamphlets were recruited. METHODS: Eligible and consenting participants underwent a validated literacy study, and their literacy levels were classified as adequate, barely adequate, marginal, or inadequate. They were then randomized to receive educational pamphlets written at either a grade 5 (intervention group) or grade 10 (control group) reading level. Comprehension of and preference for the material were determined by analysis of cloze testing and a feedback questionnaire. RESULTS: Of 199 participants, 179 were included in the analysis. The literacy testing found that 35% of patients in the community practice and 30% in the tertiary care academic centre had "marginal" or "inadequate" literacy skills, but there was no significant difference between sites (p = 0.77). Comprehension of the educational material was higher in the intervention group versus the control group (p = 0.0057), with a mean cloze score of 57.9% in the intervention group and 48.3% in the control group. The intervention group spent significantly less time reading the pamphlets (p < 0.0001), with an average of 2.52 minutes compared with 4.51 minutes. The feedback survey indicated that patients found the pamphlet with the lower reading level easier to read (p = 0.02), which was reflected in their comments as well. CONCLUSIONS: In both academic and community practice settings, about 30% of patients with glaucoma have marginal or inadequate literacy skills. However, regardless of practice, all patients better comprehend, and were more receptive to, educational material written at grade 5 reading level with illustrations, regardless of initial literacy level.

A turbulent wake as a tracer of 30,000 years of Mira's mass loss history.

Mira is one of the first variable stars ever discovered and it is the prototype (and also the nearest example) of a class of low-to-intermediate-mass stars in the late stages of stellar evolution. These stars are relatively common and they return a large fraction of their original mass to the interstellar medium (ISM) (ref. 2) through a processed, dusty, molecular wind. Thus stars in Mira's stage of evolution have a direct impact on subsequent star and planet formation in their host galaxy. Previously, the only direct observation of the interaction between Mira-type stellar winds and the ISM was in the infrared. Here we report the discovery of an ultraviolet-emitting bow shock and turbulent wake extending over 2 degrees on the sky, arising from Mira's large space velocity and the interaction between its wind and the ISM. The wake is visible only in the far ultraviolet and is consistent with an unusual emission mechanism whereby molecular hydrogen is excited by turbulent mixing of cool molecular gas and shock-heated gas. This wind wake is a tracer of the past 30,000 years of Mira's mass-loss history and provides an excellent laboratory for studying turbulent stellar wind-ISM interactions.

Comparison between central corneal thickness measurements by ultrasound pachymetry and optical coherence tomography.

PURPOSE: Measurement of central corneal thickness (CCT) plays an important role in both diagnostic and therapeutic assessment of ocular diseases. Although ultrasound pachymetry (U-PACH) is regarded as the golden standard for measurement of CCT, optical coherence tomography (OCT) may offer advantages as it can locate the central cornea with precision with no corneal touch. Nevertheless, the agreement of OCT with U-PACH has not yet been gauged by Bland-Altman analysis. This study compares CCT measurement by OCT with that by U-PACH. METHODS: Healthy subjects without ocular abnormality (except refractive errors less than or equal to -6.0 D), contact lens wear or ocular surgery were recruited. CCT was measured in one eye of normal subjects using OCT and U-PACH. Results were compared using correlation and Bland-Altman plots. RESULTS: Fifty subjects were recruited. Mean +/- SD CCT measured by OCT was 565 +/- 33 microm. This was highly correlated (Pearson's coefficient = 0.934) with the mean thickness measured by U-PACH (543 +/- 33 microm). The coefficients of variation were good and comparable at 7.9% for U-PACH and 3.5% for OCT. Compared with U-PACH, OCT consistently overestimated the CCT by a mean of 23 microm as shown on Bland-Altman plot. CONCLUSION: CCT measured by OCT and U-PACH is highly correlated. With appropriate adjustment factor, OCT agrees well with U-PACH and is a reliable alternative for CCT measurement.

Prevalence and mechanism of appositional angle closure in acute primary angle closure after iridotomy.

PURPOSE: A prospective observational case series to assess the prevalence of appositional angle closure in darkness among iridotomized Chinese eyes after acute primary angle closure (APAC) with the use of both clinical methods and ultrasound biomicroscopy. METHODS: Sixteen Chinese patients who had history of APAC and subsequent successful treatment with laser peripheral iridotomy were examined. Fourteen additional control subjects were studied. Gonioscopy and ultrasound biomicroscopic examination were performed in the dark. Gonioscopic appearance of the angle was assessed, and quantitative measurements of the angle from the ultrasound biomicroscopic images were taken. RESULTS: Of the APAC eyes 55.6% had appositionally closed angle clinically and in 38.9% only Schwalbe's line was visible on gonioscopy. Ultrasound biomicroscopy confirmed structurally different anterior segments between eyes with APAC and the control eyes. In particular, the trabecular-ciliary-process distances were markedly different between the two groups. CONCLUSION: This study documented a high prevalence of appositional closure in iridotomized eyes after APAC in Chinese patients. The anteriorly positioned ciliary body, as documented in these cases by ultrasound biomicroscopy, is the likely mechanism of the angle crowding in this patient population.

Descemet membrane detachment caused by hydrogen peroxide injury.

OBJECTIVE: To describe a patient who developed a Descemet membrane detachment after hydrogen peroxide injury with successful reattachment by intracameral injection of sulfur hexafluoride gas. METHODS: Case report. RESULTS: The right eye of a 40-year-old man was exposed to 35% hydrogen peroxide. This resulted in a central corneal epithelial defect, corneal edema, a localized detachment of Descemet membrane, and a gas bubble between the posterior corneal stroma and Descemet membrane. The Descemet membrane detachment persisted after reabsorption of the gas bubble. Successful reattachment of Descemet membrane was achieved with injection of 0.15 mL of 20% sulfur hexafluoride gas into the anterior chamber. CONCLUSION: Hydrogen peroxide ocular injury may cause Descemet membrane detachment, and successful reattachment may be achieved with intracameral injection of 20% sulfur hexafluoride gas.

Fornix-based trabeculectomy using the 'anchoring' corneal suture technique.

AIM: To assess the safety and efficacy of fornix-based tra-beculectomy with the 'anchoring' corneal suture technique in Chinese patients. METHODS: A retrospective non-comparative case series of 66 eyes of 63 Chinese patients who underwent fornix-based trabeculectomy combined with intraoperative mitomycin C (MMC) 0.4 mg/mL for 2-5 min were studied. Conjunctival wound closure of all eyes was with the anchoring corneal suture technique using a 9-0 nylon suture to prevent leakage at the corneolimbal interface. The success rate, with or without anti-glaucoma medication, the complication rate and the longevity of the drainage blebs were analyzed. RESULTS: At a mean follow-up period of 447.36 +/- 337.98 days, the mean intraocular pressure decreased from 26.83 +/- 7.90 mmHg to 17.74 +/- 8.74 mmHg (P < 0.001). The mean glaucoma medication decreased from 2.95 +/- 0.98 preoperatively to 1.23 +/- 1.41 postoperatively (P < 0.001). Thirty-one eyes (47.0%) required no anti-glaucoma medication postoperatively. Twenty eyes (30.3%) had qualified success postoperatively. Eight eyes (12.1%) had early wound leakage that resolved with conservative treatment. Three eyes (4.5%) required surgical repair. One eye (1.5%) had hypotonous maculopathy. No other major complications were encountered. CONCLUSION: Fornix-based trabeculectomy with adjunctive mitomycin C employing the anchoring corneal suture technique appears to be both safe and effective in Chinese patients.

Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding.

To further evaluate the bioenergetic role of phosphocreatine, we assessed several parameters in normal and depleted rat hearts. Rats were fed (8 weeks) a diet containing either 1% beta-guanidinoproprionic acid or 2% beta-guanidinobutyric acid (beta-GBA), resulting in an 80% phosphocreatine depletion compared to controls. Left ventricular pressure-volume curves were obtained to determine contractile function. At any volume, the developed pressure in depleted hearts was lower than in controls. At the plateau, the rate-pressure product was between 37-45% lower: 34,000 (beta-GBA), 30,174 (beta-guanidinoproprionic acid) versus 54,400 (control). 31P NMR spectroscopy on beta-GBA-treated hearts obtained the [ATP] and [phosphocreatine], which with saturation transfer estimated the rates of creatine kinase and ATP production. In depleted hearts, the rate constant for ATP synthesis from phosphocreatine was increased 33%. However, the flux was 72% lower. ATP production from ADP and Pi were similar under normal conditions, in spite of higher rates of oxygen consumption in the depleted hearts. The addition of 50 mM creatine to control perfusate had no effect on function or high energy phosphates. In contrast, a 28% increase in function and a 52% increase in [phosphocreatine] was seen in beta-GBA hearts. There was a marked increase in free [ADP] in beta-GBA hearts, resulting in a lower estimated ATP phosphorylation potential. Overall, the results suggest that phosphocreatine may play an important function by optimizing the thermodynamics of cardiac high energy phosphate utilization.

An assessment of crystalloid solutions for donor heart preservation.

The optimal technique for donor heart protection remains controversial. One component of preservation is the transport solution. Although saline solution is most frequently used as a transport medium, other crystalloid solutions may be superior. Accordingly, human right atrial trabeculae contracting isometrically in vitro were used to assess five crystalloid solutions at two different temperatures (12 degrees and 4 degrees C): St. Thomas' Hospital solution, modified Krebs-Henseleit (K+ = 16 mEq/L), Krebs-Henseleit (K+ = 4.5 mEq/L, saline, and Euro-Collins. After a 24-hour preservation period the muscles were restimulated at 34 degrees C and recovery of function was monitored for 30 minutes. Recovery of developed force was not affected by temperature (p = 0.13 by two-way analysis of variance). However, St. Thomas' Hospital solution provided the best recovery of developed force (103.3 +/- 6.2% of control) compared with saline, which had the worst developed force (2.8% +/- 1.3%) (p less than 0.002). Modified Krebs-Henseleit, Krebs-Henseleit, and Euro-Collins demonstrated intermediate performance. Although there were no differences between groups in recovery of resting force, it was greater in all groups with muscles cooled to 4 degrees C (238.7% +/- 17.6% of control) (p less than 0.001). Dry/wet weight ratios did not demonstrate statistically significant differences between groups. We conclude that, of the solutions tested, St. Thomas' Hospital solution provides the best preservation of atrial myocardium. Storage in crystalloid solutions leads to impaired relaxation, which is more apparent in tissue cooled to 4 degrees C and does not appear to be solely due to increased tissue swelling.

The human atrial trabecula: effects of calcium and temperature.

The human atrial trabecular preparation is an in vitro model which has been used to evaluate drugs and conditions to which cardiac muscle is exposed perioperatively. During its development, modifications have been made to this preparation. Two important components affecting myocardial muscle contraction are temperature and calcium concentration of the muscle bath medium. Previously, these parameters were determined independently of one another and found to be 34 degrees C and 2.5 mM calcium in a minimal Tyrode's buffer with glucose. This study was undertaken to define the optimal temperature and calcium concentration which would result in the highest yield of muscles that satisfied rigorous criteria for acceptability: developed force (DF) greater than 0.8 g, resting force (RF) less than 0.7 g, cross-sectional area less than or equal to 1.0 mm2). A total of 134 trabeculae were tested using a modified Krebs-Henseleit buffer, enriched with Eagles' medium and containing either 1.25 or 2.5 mM calcium at 34 or 37 degrees C. The trabeculae contracting in 2.5 mM calcium at 37 degrees C resulted in the highest yield of 26% while those maintained at 34 degrees C in either 1.25 or 2.5 mM calcium led to 20 and 15% useful preparations respectively (P = N.S.). Trabeculae contracting at 37 degrees C in 1.25 mM calcium resulted in the poorest yield of 8% (P = 0.002). There is a small (5 to 7%), but significant (P = 0.02), decrease in DF in 1 h when all groups were analyzed together. The exclusion criteria which are applied eliminate variability due to disease and/or treatment, therefore only 20 to 25% are acceptable for study. In summary, with well-defined and stringently applied criteria, the human right atrial trabecular preparation can be a reliable and reproducible model functioning at 37 degrees C and 2.5 mM calcium for a variety of studies.

The effect of mono(2-ethylhexyl)phthalate on an isolated perfused rat heart-lung preparation.

Di(2-ethylhexyl)phthalate (DEHP), the plasticizer used in the biomedical production of blood storage bags, hemodialysis systems, cardiopulmonary bypass (CPB) circuitry, and intubation tubes, is extracted from the plastic material when it comes into contact with biological fluids and is converted to its principal metabolite, mono(2-ethylhexyl)phthalate (MEHP). We have shown that MEHP causes cardiac and respiratory arrest, as well as hypotension, when infused into anesthetized rats. Using a well-ventilated in vitro rat heart-lung preparation, we investigated the effect of MEHP on pulmonary artery pressure (PAP) and found that MEHP had a hypertensive effect on the pulmonary vasculature ending in constriction and edema. There was a significant increase of 0.58 mm Hg/min in the PAP of isolated rat lungs when perfused with MEHP dissolved in Krebs-Henseleit (K-H) buffer (p = 0.0003). The rat lungs that were perfused with K-H buffer only increased 0.094 mm Hg/min during the same perfusion time of 20 min. The water gained during this time was 0.22 g/min with MEHP in the buffer compared to 0.04 g/min with buffer alone. The pO2 in the effluent did not decrease during the perfusion time. The concentration of MEHP in the rat lungs after perfusion varied from 20 to 40 micrograms/g. Although the mechanism of action of MEHP on PAP is too complex to be fully elucidated by this model, the increase in PAP which we have demonstrated is significant and adds yet another toxic effect of this major metabolite of the ubiquitous plasticizer, DEHP.

Atropine inhibition of the cardiodepressive effect of mono(2-ethylhexyl)phthalate on human myocardium.

Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer in polyvinylchloride (PVC)-derived plastic. Mono(2-ethylhexyl)phthalate (MEHP), the major metabolite of DEHP, had a reversible, concentration-dependent (15-200 micrograms/ml) negative inotropic effect on a human in vitro atrial trabecular isometric preparation with an IC50 of 85 micrograms/ml. When atropine (22-32 micrograms/ml) was included in the atrial preparation the IC50 was shifted to greater than 120 micrograms/ml, suggesting that MEHP acts in part through the cholinergic receptors.

Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass.

Di(2-ethylhexyl)phthalate and its principal metabolite, mono(2-ethylhexyl)phthalate, are contaminants of blood that are extracted on contact with polyvinylchloride surfaces, such as blood collection bags and tubing used in cardiopulmonary bypass. In this study, levels of the two plasticizers were measured in patients who underwent coronary artery bypass grafting, orthotopic transplantation, implantation of the Jarvik 7-70 total artificial heart during bridge-to-transplant procedures, and in infants who underwent corrective operations for congenital defects. In all adult patients the levels of di(2-ethylhexyl)phthalate increased tenfold by the end of cardiopulmonary bypass, whereas the levels of mono(2-ethylhexyl)phthalate increased ninefold. In infants, levels of di(2-ethylhexyl)phthalate rose seven times by the end of bypass and mono(2-ethylhexyl)phthalate rose significantly as well. In most of the patients having coronary bypass, the two plasticizers declined to preoperative levels within 24 hours. However, in some of the patients having orthotopic transplantation and in those in whom the Jarvik 7-70 total artificial heart was used as a bridge to transplant, the levels were still detectable 120 hours postoperatively. Circulating levels of mono(2-ethylhexyl)phthalate are only 20- to 35-fold lower in patients undergoing cardiac operations than the level of mono(2-ethylhexyl)phthalate causing a 50% reduction in developed contractile force and arrhythmias in an in vitro human atrial trabecular preparation. This study shows that patients with multisystem failure and infants may be at risk for this acute exposure to mono(2-ethylhexyl)phthalate.