RESUMEN
Quantum chemical calculations using ab initio methods at the MRCI+Q(8,9)/def2-QZVPPD and CCSD(T)/def2-QZVPPD levels as well as using density functional theory are reported for the diatomic molecules AeN- (Ae=Ca, Sr, Ba). The anions CaN- and SrN- have electronic triplet (3Π) ground states with nearly identical bond dissociation energies De ~57â kcal/mol calculated at the MRCI+Q(8,9)/def2-QZVPPD level. In contrast, the heavier homologue BaN- has a singlet (1Σ+) ground state, which is only 1.1â kcal/mol below the triplet (3Σ-) state. The computed bond dissociation energy of (1Σ+) BaN- is 68.4â kcal/mol. The calculations at the CCSD(T)-full/def2-QZVPPD and BP86-D3(BJ)/def2-QZVPPD levels are in reasonable agreement with the MRCI+Q(8,9)/def2-QZVPPD data, except for the singlet (1Σ+) state, which has a large multireference character. The calculated atomic partial charges given by the CM5, Voronoi and Hirshfeld methods suggest small to medium-sized AeâN- charge donation for most electronic states. In contrast, the NBO method predicts for all species medium to large AeâN- electronic charge donation, which is due to the neglect of the (n)p AOs of Ae atoms as genuine valence orbitals. Neither the bond orders nor the bond lengths correlate with the bond dissociation energies. The EDA-NOCV calculations show that the heavier alkaline earth atoms Ca, Sr, Ba use their (n)s and (n-1)d orbitals for covalent bonding.
RESUMEN
Unlike graphene derived from graphite, borophenes represent a distinct class of synthetic two-dimensional materials devoid of analogous bulk-layered allotropes, leading to covalent bonding within borophenes instead of van der Waals (vdW) stacking. Our investigation focuses on 665 vdW-stacking boron bilayers to uncover potential bulk-layered boron allotropes through vdW stacking. Systematic high-throughput screening and stability analysis reveal a prevailing inclination toward covalently bonded layers in the majority of boron bilayers. However, an intriguing outlier emerges in δ5 borophene, demonstrating potential as a vdW-stacking candidate. We delve into electronic and topological structural similarities between δ5 borophene and graphene, shedding light on the structural integrity and stability of vdW-stacked boron structures across bilayers, multilayers, and bulk-layered allotropes. The δ5 borophene analogues exhibit metallic properties and characteristics of phonon-mediated superconductors, boasting a critical temperature near 22 K. This study paves the way for the concept of "borophite", a long-awaited boron analogue of graphite.
RESUMEN
The presence of a delocalized π-bond is often considered an essential criterion for achieving planar hypercoordination. Herein, we show that σ-delocalization could be sufficient to make the planar configuration the most stable isomer in a series of planar pentacoordinate s-block metals. High-level ab initio computations reveal that the global minimum of a series of interalkali and interalkali-alkaline earth clusters (LiNa5, Li5Mg+, Na5Mg+, K5Ca+, CaRb5+, Rb5Sr+, and SrCs5+) adopts a singlet D5h structure with a planar pentacoordinate lithium or alkaline earth metal (AE = Mg, Ca, Sr). These clusters are unusual combinations to stabilize a planar pentacoordinate atom, as all their constituents are electropositive. Despite the absence of π-electrons, Hückel's rule is fulfilled by the six σ-electrons. Furthermore, the systems exhibit a diatropic ring current in response to an external magnetic field and a strong magnetic shielding, so they might be classified as σ-aromatic. Therefore, multicenter σ-bonds and the resulting σ-delocalization stabilize these clusters, even though they lack π-aromaticity.
RESUMEN
Planar hexacoordination (ph) is only rarely reported in the literature. So far, only a few neutral and cationic molecules possessing phE (E = C, Si, B, Al, Ga) in the most stable isomer are predicted theoretically. Present electronic structure calculations report hitherto unknown anionic planar hexcoordinate beryllium and magnesium, phBe/Mg, as the most stable isomer. Global minimum searches show that the lowest energy structure of BeC6M3- (M = Al, Ga) and MgC6M3- (M = Ga, In, Tl) is the D3h symmetric phBe/Mg clusters, where beryllium/magnesium is covalently bonded with six carbon centers and M is located in a bridging position between two carbon centers. These global minimum phBe/Mg clusters are highly kinetically stable against isomerization, facilitating the experimental confirmation by photoelectron spectroscopy. Noteworthy is the fact that the phBe/Mg center is linked with carbon centers through three 7c-2e delocalized σ bonds and three 7c-2e π bonds, making the cluster double aromatic (σ + π) in nature. The bonding between the Be/Mg and outer ring moiety can be best expressed as an electron-sharing σ-bond between the s orbital of Be+/Mg+ and C6M32- followed by three dative interactions involving empty pπ and two in-plane p orbitals of Be/Mg. Furthermore, Lewis basic M centers of the title clusters can be passivated through the complexation with bulky Lewis acid, 9-boratriptycene, lowering the overall reactivity of the cluster, which can eventually open up the possibility of their large-scale syntheses.
RESUMEN
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders in child and adolescent psychiatry, with a prevalence of more than 5%. Despite extensive research on ADHD in the last 10 to 20 years, effective treat-ments are still lacking. Instead, the concept of ADHD seems to have become broader and more heterogeneous. Therefore, the diagnosis and treatment of ADHD remains challenging for clinicians. AIM: To investigate the effects of a multimodal integrated intervention for children with ADHD. METHODS: Between March 2019 and September 2020, a total of 100 children with ADHD who were diagnosed and treated at our hospital were assessed for eligibility, two of whom revoked their consent. A case-control study was conducted in which the children were equally assigned, using a randomized number table, to either a medication group (methylphenidate hydrochloride extended-release tablets and atomoxetine hydrochloride tablets) or a multimodal integrated intervention group (medication + parent training + behavior modification + sensory integration therapy + sand tray therapy), with 49 patients in each group. The clinical endpoint was the efficacy of the different intervention modalities. RESULTS: The two groups of children with ADHD had comparable patient characteristics (P > 0.05). Multimodal integrated intervention resulted in a significantly higher treatment efficacy (91.84%) than medication alone (75.51%) (P < 0.05). Children who received the multimodal integrated intervention showed lower scores in the Conners Parent Symptom Questionnaire and the Weiss Functional Impairment Rating Scale than those treated with medication alone (P < 0.05). The Sensory Integration Scale scores of children in the multimodal integrated intervention group were higher than those of children in the medication group (P < 0.05). Children who received the multimodal integrated intervention had higher compliance and family satisfaction and a lower incidence of adverse events than those treated with medication alone (P < 0.05). CONCLUSION: Multimodal integrated intervention effectively alleviated symptoms associated with ADHD in children. It enhanced their memory and attention with high safety and parental satisfaction, demonstrating good potential for clinical promotion.
RESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) is closely associated with gastric diseases and has a high prevalence in China. Public platforms are considered common and important tools to publicize H. pylori-related information. This study aimed to assess and compare the content and quality of H. pylori-related videos on TikTok and Bilibili. MATERIALS AND METHODS: A search was performed on the TikTok and Bilibili platforms using the keyword "H. pylori". The source of upload was categorized as for-profit organizations, general users, health professionals, news agencies, nonprofit organizations, and science communicators. The Journal of American Medical Association (JAMA), Global Quality Scale (GQS), and modified DISCERN scores were used to evaluate the quality of the included videos. RESULTS: A total of 93 TikTok videos and 79 Bilibili videos were included and analyzed. TikTok videos had a significantly shorter duration than Bilibili videos (64 vs. 149 s, respectively; p < 0.001). The duration of the video showed a positive correlation with the modified DISCERN and GQS scores (p < 0.001, r = 0.388 and r = 0.437, respectively). The JAMA and modified DISCERN scores of the TikTok video were significantly higher in health professionals and nonprofit organizations than in other sources (p < 0.05). For Bilibili, science communicators had a significantly higher JAMA score than the other video sources (p < 0.001). The videos uploaded by news agencies received more views, comments, shares, and favorites than any other organization or individual (p < 0.001). CONCLUSIONS: In China, H. pylori-related videos from TikTok and Bilibili tended to provide the information regarding the transmission and eradication of H. pylori. However, many videos scored an average rating in content and quality and need to be improved. We recommend that the public obtain H. pylori-related information through videos uploaded by health professionals, nonprofit organizations, and science communicators.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Medios de Comunicación Sociales , Humanos , Helicobacter pylori/genética , Fuentes de Información , China , Reproducibilidad de los ResultadosRESUMEN
Correction for 'Structure and bonding of molecular stirrers with formula B7M2- and B8M2 (M = Zn, Cd, Hg)' by Rui Yu et al., Phys. Chem. Chem. Phys., 2020, 22, 12312-12320, https://doi.org/10.1039/D0CP01603A.
RESUMEN
The achievement of the rule-breaking planar hypercoordinate motifs (carbon and other elements) is mainly attributed to a practical electronic stabilization mechanism, where the bonding of the central atom pz π electrons is a crucial issue. We have demonstrated that strong multiple bonds between the central atom and partial ligands can be an effective approach to explore stable planar hypercoordinate species. A set of planar tetra-, penta- and hexa-coordinate silicon clusters were herein found to be the lowest-energy structure, which can be viewed as decorating SiO3 by alkali metals in the MSiO3 - , M2 SiO3 and M3 SiO3 + (M=Li, Na) clusters. The strong charge transfer from M atoms to SiO3 effectively results in [M]+ SiO3 2- , [M2 ]2+ SiO3 2- and [M3 ]3+ SiO3 2- salt complexes, where the Si-O multiple bonding and structural integrity of the Benz-like SiO3 framework is maintained better than the corresponding SiO3 2- motifs. The bonding between M atoms and SiO3 motif is best described as M+ forming a few dative interactions by employing its vacant s, p, and high-lying d orbitals. These considerable MâSiO3 interactions and Si-O multiple bonding give rise to the highly stable planar hypercoordinate silicon clusters.
RESUMEN
BACKGROUND: Long-term treatment of attention deficit/hyperactivity disorder (ADHD) is associated with adverse events, such as nausea and vomiting, dizziness, and sleep disturbances, and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients' social functioning. AIM: To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD. METHODS: A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group (methylphenidate hydrochloride and tomoxetine hydrochloride) or the non-pharmacological group (parental training, behavior modification, sensory integration therapy, and sand tray therapy), with 45 cases in each group. Outcome measures included treatment compliance, Swanson, Nolan, and Pelham, Version IV (SNAP-IV) scores, Conners Parent Symptom Questionnaire (PSQ) scores, and Weiss Functional Impairment Rating Scale (WFIRS) scores. RESULTS: The non-pharmacological interventions resulted in significantly higher compliance in patients (95.56%) compared with medication (71.11%) (P < 0.05). However, no significant differences in SNAP-IV and PSQ scores, in addition to the learning/school, social activities, and adventure activities of the WFIRS scores were observed between the two groups (P > 0.05). Patients with non-pharmacological interventions showed higher WFIRS scores for family, daily life skills, and self-concept than those in the pharmacological group (P < 0.05). CONCLUSION: Non-pharmacological interventions, in contrast to the potential risks of adverse events after long-term medication, improve patient treatment compliance, alleviate patients' behavioral symptoms of attention, impulsivity, and hyperactivity, and improve their cognitive ability, thereby improving family relationships and patient self-evaluation.
RESUMEN
Quantum chemical calculations using ab initio methods at the MRCI+Q(6,8)/def2-QZVPP and CCSD(T)/def2-QZVPP levels as well as density functional theory are reported for the diatomic molecules AeB- and isoelectronic AeC (Ae=Ca, Sr, Ba). The boride anions AeB- have an electronic triplet (3 Σ- ) ground state. The quintet (5 Σ- ) state is 5.8-12.3â kcal/mol higher in energy and the singlet (1 Δ) state is 13.1-15.3â kcal/mol above the triplet. The isoelectronic AeC molecules are also predicted to have a low-lying triplet (3 Σ- ) state but the quintet (5 Σ- ) state is only 2.2â kcal/mol (SrC) and 2.9â kcal/mol (CaC) above the triplet state. The triplet (3 Σ- ) and quintet (5 Σ- ) states of BaC are nearly isoenergetic. All systems have rather strong bonds. The calculated bond dissociation energies of the triplet (3 Σ- ) state are between De =38.3-41.7â kcal/mol for AeB- and De =49.4-57.5â kcal/mol for AeC. The barium species have always the strongest bonds whereas the calcium and strontium compounds have similar BDEs. The bonding analysis indicates that there is little charge migration in AeB- in the direction AeâB- where the alkaline earth atoms carry positive charges between 0.09â e-0.22â e. The positive charges at the Ae atoms are much larger in AeC where the charge migration AeâC is between 0.90â e-0.91â e. A detailed analysis of the interatomic interactions with the EDA-NOCV method shows that all diatomic species AeB- and AeC are built from dative interactions between Ae (1 S, ns2 ) and B- or C (3 P, 2â s2 2pπ 1 2pπ' 1 ). The eventually formed bonds in AeC are better described in terms of interactions between the ions Ae+ (2 S, ns1 )+C- (4 S, 2â s2 2pπ 1 2pπ' 1 2pσ 1 ). Inspection of the orbital interactions suggests that the alkaline earth atoms Ca, Sr, Ba use mainly their (n-1)d AOs besides the (n)s AOs for the covalent bonds. This creates a second energetically low-lying σ-bonding MO in the molecules, which feature valence orbitals with the order Ï1 (σ-bonding)<Ï2 (σ-bonding)<Ï3 (degenerate π-bonding). All four occupied valence MOs of AeB- and AeC are bonding orbitals. Since the degenerate π orbitals Ï3 are only singly occupied, the formal bond order is three.
RESUMEN
Because of the electron deficiency of boron, a triangular network with planar hexacoordination is the most common structural and bonding property for isolated boron clusters and two-dimensional (2D) boron sheets. However, this network is a rule-breaking structure and bonding case for all other main-group elements. Herein, the Be2M (M = Al and Ga) 2D monolayer with P6/mmm space group was found to be the lowest-energy structure with planar hexacoordinate Be/Al/Ga motifs. More interestingly, Be2Al and Be2Ga were observed to be intrinsic phonon-mediated superconductors with a superconducting critical temperature (Tc) of 5.9 and 3.6 K, respectively, where compressive strain could further enhance their Tc. The high thermochemical and kinetic stability of Be2M make a promising candidate for experimental realization, considering its high cohesive energy, absence of soft phonon modes, and good resistance to high temperature. Moreover, the feasibility of directly growing Be2M on the electride Ca2N substrate was further demonstrated, where its intriguing electronic and superconducting properties were well maintained in comparison with the freestanding monolayer. The Be2M monolayer with rule-breaking planar hexacoordinate motifs firmly pushes the ultimate connection of the "anti-van't Hoff/Le Bel" structure with promising physical properties.
RESUMEN
Using a starlike Be6Au7 - cluster as a building block and following the bottom-up strategy, an intriguing two-dimensional (2D) binary s-block metal Be2Au monolayer with a P6/mmm space group was theoretically designed. Both the Be6Au7 - cluster and the 2D monolayer are global minima featuring rule-breaking planar hexacoordinate motifs (anti-van't Hoff/Le Bel arrangement), and their high stabilities are attributed to good electron delocalization and electronic-stabilization-induced steric force. Strikingly, the Be2Au monolayer is a rare Dirac material with two perfect Dirac node-loops in the band structure and is a phonon-mediated superconductor with a critical temperature of 4.0 K. The critical temperature can be enhanced up to 11.0 K by applying compressive strain at only 1.6%. This study not only identifies a new binary s-block metal 2D material, namely Be2Au, which features planar hexacoordination, and a candidate superconducting material for further explorations, but also provides a new strategy to construct 2D materials with novel chemical bonding.
RESUMEN
The occurrence of planar hexacoordination is very rare in main group elements. We report here a class of clusters containing a planar hexacoordinate silicon (phSi) atom with the formula SiSb3M3 + (M = Ca, Sr, Ba), which have D 3h (1A1') symmetry in their global minimum structure. The unique ability of heavier alkaline-earth atoms to use their vacant d atomic orbitals in bonding effectively stabilizes the peripheral ring and is responsible for covalent interaction with the Si center. Although the interaction between Si and Sb is significantly stronger than the Si-M one, sizable stabilization energies (-27.4 to -35.4 kcal mol-1) also originated from the combined electrostatic and covalent attraction between Si and M centers. The lighter homologues, SiE3M3 + (E = N, P, As; M = Ca, Sr, Ba) clusters, also possess similar D 3h symmetric structures as the global minima. However, the repulsive electrostatic interaction between Si and M dominates over covalent attraction making the Si-M contacts repulsive in nature. Most interestingly, the planarity of the phSi core and the attractive nature of all the six contacts of phSi are maintained in N-heterocyclic carbene (NHC) and benzene (Bz) bound SiSb3M3(NHC)6 + and SiSb3M3(Bz)6 + (M = Ca, Sr, Ba) complexes. Therefore, bare and ligand-protected SiSb3M3 + clusters are suitable candidates for gas-phase detection and large-scale synthesis, respectively.
RESUMEN
Purpose: Snoring or obstructive sleep apnea, with or without uncontrolled hypertension, is common and significantly increases the risk of coronary heart disease (CHD). The aim of this study was to develop and validate a prognostic model to predict and identify high-risk patients for CHD among snorers with uncontrolled hypertension. Methods: Records from 1,822 snorers with uncontrolled hypertension were randomly divided into a training set (n = 1,275, 70%) and validation set (n = 547, 30%). Predictors for CHD were extracted to construct a nomogram model based on multivariate Cox regression analysis. We performed a single-split verification and 1,000 bootstraps resampling internal validation to assess the discrimination and consistency of the prediction model using area under the receiver operating characteristic curve (AUC) and calibration plots. Based on the linear predictors, a risk classifier for CHD could be set. Results: Age, waist circumference (WC), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) were extracted as the predictors to generate this nomogram model. The C-index was 0.720 (95% confidence interval 0.663-0.777) in the derivation cohort and 0.703 (0.630-0.776) in the validation cohort. The AUC was 0.757 (0.626-0.887), 0.739 (0.647-0.831), and 0.732 (0.665-0.799) in the training set and 0.689 (0.542-0.837), 0.701 (0.606-0.796), and 0.712 (0.615-0.808) in the validation set at 3, 5, and 8 years, respectively. The calibration plots showed acceptable consistency between the probability of CHD-free survival and the observed CHD-free survival in the training and validation sets. A total of more than 134 points in the nomogram can be used in the identification of high-risk patients for CHD among snorers with uncontrolled hypertension. Conclusion: We developed a CHD risk prediction model in snorers with uncontrolled hypertension, which includes age, WC, HDL-C, and LDL-C, and can help clinicians with early and quick identification of patients with a high risk for CHD.
RESUMEN
We report the first planar hexacoordinate gallium (phGa) center in the global minimum of the GaBe6Au6 + cluster which has a star-like D 6h geometry with 1A1g electronic state, possessing a central gallium atom encompassed by a Be6 hexagon and each Be-Be edge is further capped by an Au atom. The electronic delocalization resulting in double aromaticity (both σ and π) provides electronic stability in the planar form of the GaBe6Au6 + cluster. The high kinetic stability of the title cluster is also understood by Born-Oppenheimer molecular dynamics simulations. The energy decomposition analysis in combination with the 'natural orbitals for chemical valence' theory reveals that the bonding in the GaBe6Au6 + cluster is best expressed as the doublet Ga atom with 4s24p⥠1 electronic configuration forming an electron-sharing π bond with the doublet Be6Au6 + moiety followed by Ga(s)â[Be6Au6 +] σ-backdonation and two sets of Ga(pâ)â[Be6Au6 +] σ-donations.
RESUMEN
Phenalenyls (PLYs) are important synthons in many functional and electronic materials, which often display favorable molecule-to-molecule overlap for electron or hole transport. They also serve as a prototype for π-stacking pancake bonding based on two-electron multicenter bonding (2e/mc). Unexpected near-doubling of the binding energy is obtained for the positively charged PLY2 + dimer with an effect similar to that seen for the positively charged olympicenyl (OPY) radical dimer. This charge effect is reversed for the perfluorinated (PF) dimers, and the negatively charged perfluorinated (PF) dimers PF-PLY2 - and PF-OPY2 - become strongly bound. Long-range interactions reflect these differences. Also surprising is that in this case the pancake bonding corresponds to single-electron (1e/mc) or a three-electron (3e/mc) multicenter bonding in contrast to the 2e/mc bonding that occurs for the neutral radical dimers. The strong preference for a large intermolecular overlap is maintained in these charged dimers. Importantly, the preference for π-bonding in the charged dimers compared to σ-bonding is strongly enhanced relative to the neutral PLY dimers.
RESUMEN
The electronic and structural prerequisites for a multi-layered molecular rotor have been demonstrated herein in terms of nine 18-valence-electron metallocene sandwich complexes. First, the lack of strong covalent bonds between layers is a key issue to obtain a barrier-free rotation of one layer relative to other layers, where the considerable energetic but unidirectional (such as electrostatic interactions) interactions are needed between layers to keep the structural integrity against fragment separation and structural distortion in a rotation process. Second, one or more layers should possess continuous and delocalized π electron clouds to provide a driving force for the barrier-free rotation. More importantly, besides a negligible rotation barrier, the reasonable rotational period associated with the ultra-soft rotation mode is a critical point for the observability of dynamical behavior in multi-layered molecular rotors.
RESUMEN
The triply bonded heavier main-group compounds have a textbook trans-bent geometry, in contrast to a familiar linear form found for the lightest analogues. Strikingly, the unexpected linear group 13 E≡E triple bonds were herein found in the D4h -symmetry E2 Li6 2+ clusters, and they possess a large barrier (>18.0â kcal/mol) towards the dissociation of Li+ . The perfectly surrounded Li4 motifs and two linear coordinated Li atoms strongly suppress the increasing nonbonded electron density of heavier E atoms, making two degenerate π bonds and one multi-center σ bond in linear heavier main-group triple bonds. The surrounding Li6 motifs not only creates an effective electronic structure to form a linear E≡E triple bond, but the resulting electrostatic interactions account for the highly stable global E2 Li6 2+ clusters.
RESUMEN
PURPOSE: Primary aldosteronism (PA) remains, to a large extent, an under-diagnosed disease. We aimed to develop and validate a novel clinical nomogram to predict PA based on routine biochemical variables including new ones, calcium-phosphorus product. METHODS: Records from 806 patients with hypertension were randomly divided into 70% (n = 564) as the training set and the remaining 30% (n = 242) as the validation set. Predictors for PA were extracted to construct a nomogram model based on regression analysis of the training set. An internal validation was performed to assess the nomogram model's discrimination and consistency using the area under the curve for receiver operating characteristic curves and calibration plots. The diagnostic accuracy was compared between nomogram and other known prediction models, using receiver operating characteristics (ROC) and decision curve analyses (DCA). RESULTS: Female gender, serum potassium, serum calcium-phosphorus product, and urine pH were adopted as predictors in the nomogram. The nomogram resulted in an area under the curve of 0.73 (95% confidence interval: 0.68-0.78) in the training set and an area under the curve of 0.68 (0.59-0.75) in the validation set. Predicted probability and actual probability matched well in the nomogram (p > 0.05). Based on ROC and DCA, 21-70% threshold to predict PA in the nomogram model was clinically useful. CONCLUSIONS: We have developed a novel nomogram to predict PA in hypertensive individuals based on routine biochemical variables. External validation is needed to further demonstrate its predictive ability in primary care settings.
Asunto(s)
Hiperaldosteronismo , Hipertensión , Femenino , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/complicaciones , Hipertensión/diagnóstico , Nomogramas , Curva ROC , Análisis de RegresiónRESUMEN
The unexpected linear group 13 E[triple bond, length as m-dash]E triple bonds were herein uncovered with the D3h-symmetry E2M5+ (M = Li, Na, and K) clusters, where the linear M-E[triple bond, length as m-dash]E-M form is perfectly surrounded by M3 motifs. The increasing nonbonded electron density of the heavier main-group elements is the key issue for the trans-bent geometry, and yet it is strongly suppressed in E2M5+, creating two degenerate π bonds and one multi-center σ bond.