Anterior dynamic ultrasound and Graf's examination in neonatal hip instability.

BACKGROUND: Discrepancy between neonatal hip morphology and stability has been reported in the literature. Comparative ultrasound studies on this issue are limited. PURPOSE: To compare neonatal hip instability, as assessed by dynamic ultrasound and clinical examination, with acetabular morphology, as assessed by Graf's method. MATERIAL AND METHODS: 536 newborn infants with clinical signs of hip instability, ambiguous findings at clinical hip examination, or positive risk factors for DDH were investigated with two ultrasound methods, the Graf method and anterior dynamic ultrasound, at an average age of 12 days. The hips were allocated to three groups according to the Graf result: A, normal (type Ia and b); B, borderline or immature (type IIa); and C, pathologic (type IIc and worse). Graf examination was compared with two diagnostic tests for instability, namely clinical examination by senior pediatric orthopedists and anterior dynamic ultrasound. RESULTS: According to Graf's method, 77% of the hips were normal, 20% borderline/immature, and 3% pathologic. On clinical hip examination, 82% were stable, 14% unstable, and 4% dislocatable. The dynamic ultrasound outcome was 88% stable hips, 10% unstable, and 2% dislocatable. Of the hips considered unstable or dislocatable on dynamic ultrasound, 21% had normal (type I) and 66% immature acetabular morphology according to the Graf method. Of the hips that were stable on dynamic ultrasound, only one (0.1%) was dysplastic according to the Graf method. Graf's examination showed the smallest number of normal hips, but also the fewest pathologic hips, with many indeterminate results that needed follow-up. CONCLUSION: Acetabular morphology correlated better to stability as assessed by dynamic ultrasound than to the clinical examination results, with fair to moderate agreement. Graf's examination resulted in a large number of indeterminate results that needed follow-up, but when used as the sole criterion for deciding treatment did not lead to a higher treatment rate than when the decision was based on clinical hip examination.

Neonatal hip instability: a prospective comparison of clinical examination and anterior dynamic ultrasound.

BACKGROUND: Ultrasound is increasingly being used to complement the clinical examination in assessing neonatal hip instability. The clinical examination, although highly sensitive in detecting hip instability, can lead to considerable overtreatment. PURPOSE: To compare anterior dynamic ultrasound and clinical examination in the assessment of neonatal hip instability and regarding treatment rates. MATERIAL AND METHODS: 536 newborn infants (out of a population of 18,031) were selected, on the basis of a combination of risk factors, clinical signs of hip instability or ambiguous clinical findings, to undergo an anterior dynamic ultrasound examination of the hip, by a method developed by our group. This examination, performed by one out of seven experienced examiners, was compared with the standard clinical hip examination conducted by one of four pediatric orthopedic surgeons. The clinical examination was carried out both prior to and within a few hours after the ultrasound examination. RESULTS: The clinical examination diagnosed 81.7% of the hips as normal, 14.5% as unstable, and 3.8% as dislocatable or dislocated. With the dynamic ultrasound method, the corresponding figures were 87.8%, 10.4%, and 1.8%, respectively. Use of the criteria of the clinical examination resulted in treatment of 147 infants. Using the dynamic ultrasound examination as a criterion meant that 87 infants would receive treatment. The calculated treatment rate was 0.85% when based on the clinical stress test and 0.49% when based on the dynamic ultrasound. CONCLUSION: The dynamic ultrasound results reduced the treatment rate by over 40% when used as a basis for the decision regarding treatment.

Metacarpophalangeal pattern profile analysis as a tool for early diagnosis of Turner syndrome.

PURPOSE: To analyze the metacarpophalangeal pattern profile (MCPP) in a cohort of individuals with Turner syndrome (TS), and to assess its value as a tool for early diagnosis of TS. MATERIAL AND METHODS: Medical records and radiological material were collected of 71 patients with TS aged between 3 and 21 years. Forty-six patients received growth hormone therapy (33-66 microg kg(-1) day(-1)) and 14 of these were also treated with the anabolic steroid oxandrolone (1.25-3.75 mg day(-1)). A total of 233 frontal hand radiographs were studied and pattern profiles were calculated. Profiles of the TS patients were compared with those of 70 normal females. Mean pattern profiles were calculated for different age groups and extrapolated profiles for newborns and infants were developed. RESULTS: Our results confirm that patients with TS have a distinct MCPP which differs significantly from that of normal individuals. A bone-shortening gradient with increasing shortening from distal phalanges to metacarpals was demonstrated. We also showed that the MCPP in TS is a remarkably constant feature from 3 to 18 years. Pattern profiles did not differ significantly between the patients with 45,X and non-45,X karyotype. MCPP was not affected by treatment with growth hormone of growth hormone plus oxandrolone. Discriminant analysis yielded correct classification in 88%, of analyzed cases. CONCLUSION: TS individuals have a distinct hand pattern profile that is not age-related. MCPP analysis can be applied at any age and may facilitate early diagnosis of TS. Our study showed that MCPP analysis is a specific and sensitive method that should be considered as a routinely used tool for early diagnosis of TS in girls with unexplained short stature.

Metacarpophalangeal pattern profile analysis in Leri-Weill dyschondrosteosis.

PURPOSE: To analyze the metacarpophalangeal profile (MCPP) in individuals with Leri-Weill dyschondrosteosis (LWD) and to assess its value as a possible contributor to early diagnosis. MATERIAL AND METHODS: Hand profiles of 39 individuals with a diagnosis of LWD were calculated and analyzed. Discriminant analysis was applied to differentiate between LWD and normal individuals. RESULTS: There was a distinct pattern profile in LWD. Mean pattern profile showed two bone-shortening gradients, with increasing shortening from distal to proximal and from medial to lateral. Distal phalanx 2 was disproportionately long and second metacarpal was disproportionately short. Discriminant analysis yielded correct classification in 72% of analyzed cases. CONCLUSION: MCPP is not age-related and the analysis can be applied at any age, facilitating early diagnosis of LWD. In view of its availability, low costs, and diagnostic value, MCPP analysis should be considered as a routine method in the patients of short stature where LWD is suspected.

Appendicitis in children--impact of US and CT on the negative appendectomy rate.

BACKGROUND/PURPOSE: Ultrasonography (US) and computed tomography (CT) have proved useful for the evaluation of suspected appendicitis and were introduced as diagnostic tools at our institution about ten and five years ago, respectively. The aim of this study was to evaluate how the negative appendectomy and perforation rates have changed with increased use of US and CT. METHODS: The medical records of 600 children who underwent appendectomy during years 1991, 1994, 1997, and 2000 were reviewed. Perforation in perforated appendicitis was considered to have occurred after admission if the time interval between the first health professional contact and surgery exceeded 12 hours. RESULTS: The total number of appendectomies during the years 1991, 1994, 1997, and 2000 was 406, 334, 407, and 397, respectively. The negative appendectomy rate for the same years was 23%, 8.7%, 8.0%, and 4.0%, respectively. The overall rate of perforations and the perforation rate after admission was 32% and 12%, 34% and 7.3%, 34% and 13%, and 29% and 2.1%, respectively. The rate of patients who underwent US and CT during each period was 1.0% and 0.0%, 41% and 0.0%, 91% and 21% and 98% and 59%, respectively. CONCLUSIONS: The negative appendectomy rate has been substantially reduced after the introduction of both US and CT. The rate of perforation after admission has not increased.

Acute health effects common during graffiti removal.

OBJECTIVE: The aim of this study was to identify possible health effects caused by different cleaning agents used in graffiti removal. METHODS: In 38 graffiti removers working 8-h shifts in the Stockholm underground system, the exposure to organic solvents was assessed by active air sampling, biological monitoring, and by interviews and a questionnaire. Health effects were registered, by physical examinations, porta7ble spirometers and self-administered questionnaires. The prevalence of symptoms was compared with 49 controls working at the underground depots, and with 177 population controls. RESULTS: The 8-h time-weighted average exposures (TWA) were low, below 20% of the Swedish permissible exposure limit value (PEL) for all solvents. The short-term exposures occasionally exceeded the Swedish short-term exposure limit values (STEL), especially during work in poorly ventilated spaces, e.g. in elevators. The graffiti removers reported significantly higher prevalence of tiredness and upper airway symptoms compared with the depot controls, and significantly more tiredness, headaches and symptoms affecting airways, eyes and skin than the population controls. Among the graffiti removers, some of the symptoms increased during the working day. On a group basis, the lung function registrations showed normal values. However, seven workers displayed a clear reduction of peak expiratory flow (PEF) over the working shift. CONCLUSIONS: Though their average exposure to organic solvents was low, the graffiti removers reported significantly higher prevalence of unspecific symptoms such as fatigue and headache as well as irritative symptoms from the eyes and respiratory tract, compared with the controls. To prevent adverse health effects it is important to inform the workers about the health risks, and to restrict use of the most hazardous chemicals. Furthermore, it is important to develop good working practices and to encourage the use of personal protective equipment.

Air and biological monitoring of solvent exposure during graffiti removal.

OBJECTIVE: The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures. METHODS: Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews. RESULTS: Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and gamma-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high. CONCLUSIONS: Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the health risks and to restrict the use of the most toxic chemicals. Furthermore, it is important to develop good working procedures and to encourage the use of personal protection equipment.

Regulation and function of the Arabidopsis ABA-insensitive4 gene in seed and abscisic acid response signaling networks.

We have characterized developmental, environmental, and genetic regulation of abscisic acid-insensitive (ABI)4 gene expression in Arabidopsis. Although expressed most strongly in seeds, ABI4 transcripts are also present at low levels in vegetative tissue; vegetative expression is not induced by abscisic acid (ABA) or stress treatments. Comparison of transcript levels in mature seeds of ABA-insensitive, ABA-hypersensitive, ABA-deficient, or heterochronic mutants indicates that ABI4 expression is altered in only two of the backgrounds, the ABA-insensitive mutants abi1-1 and abi3-1. To determine whether ABI4 is necessary and/or sufficient for ABA response, we assayed the effects of loss of ABI4 function and ectopic ABI4 expression on growth and gene expression. We examined genetic interactions among three ABA response loci, ABI3, ABI4, and ABI5, by comparing phenotypes of mutants, ectopic expression lines, mutants carrying an ectopically expressed transgene, and the corresponding wild-type lines. Our results indicate some cross-regulation of expression among ABI3, ABI4, and ABI5 and suggest that they function in a combinatorial network, rather than a regulatory hierarchy, controlling seed development and ABA response.

Improved health after intervention in a school with moisture problems.

In a school with floor moisture problems, the personnel had complaints consistent with the sick-building syndrome (SBS). Interventive measures including the laying of a ventilated floor were undertaken to eliminate the emissions. To examine if the intervention resulted in positive health effects, 34 personnel and 336 pupils were interviewed just before the intervention and also 7 months after. Also were interviewed 21 personnel and 224 pupils at an adjacent school serving as a control. Compared with the control school, the problem school showed more complaints, more general symptoms and more symptoms from the eyes, airways and skin, both among the personnel and the pupils. In the post-intervention examinations, the excess of symptoms among the personnel had almost disappeared. Among the pupils, the frequency of eye irritation was reduced but a general improvement of the other symptoms was not as obvious. However, after adjustment for a recent common cold, atopy and stress among the pupils, only one symptom ("stuffy nose") remained significantly elevated. In conclusion, the intervention was followed by positive health effects, supporting the hypothesis that emissions from building material had contributed to the excess of symptoms. A recent common cold was highly related to the symptoms and should be considered in future SBS studies.

The HD-Zip gene ATHB6 in Arabidopsis is expressed in developing leaves, roots and carpels and up-regulated by water deficit conditions.

Homeodomain-leucine zipper (HD-Zip) proteins are transcription factors as yet found only in plants. We have characterized one HD-Zip gene, ATHB6, from Arabidopsis thaliana. ATHB6 was expressed constitutively in seedlings, but significantly up-regulated in seedlings subjected to water deficit, osmotic stress or exogenous treatment with abscisic acid (ABA), an induction being detectable within 30 min. The ATHB6 induction was impaired in the two ABA-insensitive mutants, abi1 and abi2, but unaffected in the abi3 mutation. The induction was ABA-dependent, since no increase in ATHB6 transcript was detected in the ABA-deficient mutant aba-3 subjected to drought treatment. These results suggest that ATHB6 may act downstream to both ABI1 and ABI2 in a signal transduction pathway mediating a drought stress response. A translational fusion of the ATHB6 promoter with the reporter gene GUS (ATHB6::GUS) in transgenic A. thaliana plants showed high-level expression in leaf primordia. Expression in developing cotyledons, leaves, roots and carpels was restricted to regions of cell division and/or differentiation. The expression in the cotyledons was detectable in the epidermis and high in the stomatal cells. In mature cotyledons and leaves the marker gene was expressed only in the vascular tissue. These expression data suggest ATHB6 to have a function related to cell division and/or differentiation in developing organs.

Mercury inductions in persons with subjective symptoms alleged to dental amalgam fillings.

This study was carried out to determine whether health disturbances alleged to mercury release from dental amalgam fillings, i.e. "amalgam disease", may be caused by an increased sensitivity to mercury (Hg). In the form of a double-blind test, 39 volunteers who themselves suspected "amalgam disease" inhaled small doses of mercury vapour (0.6-10 microg) or pure air in a random sequence. After the induction procedure, the test persons assessed whether they reacted or not, i.e. experienced increased illness or not. The test persons also registered the daily intensity of their various symptoms. Calculated on the whole population, there was no statistically significant difference between the number of reactions after inhalation of mercury vapour compared with after inhalation of air. Two subjects, however, reacted significantly more often to mercury vapour than to air. The results do not support that short-term exposure to low doses of Hg vapour in general promotes clinical illness in subjects who themselves suspect "amalgam disease". The deviating reactions presented by two test persons, however, may support the theory that occasional individuals can be sensitive to very low doses of Hg.

Hypersensitivity to electricity: working definition and additional characterization of the syndrome.

Those who believe that electric appliances trigger adverse symptoms have coined the label hypersensitivity to electricity. Scientific research has not been able to identify a direct link between electromagnetic fields and symptoms, and no diagnostic criteria exist. Groups with reported hypersensitivity are very heterogeneous. A need exists for an operational working definition and improved characterization of groups. We report an investigation of symptoms and risk indicators associated with reported hypersensitivity to electricity-based on a survey at a high-technology, multinational telecommunications corporation. Comparisons are also made with patients referred to a university department of occupational and environmental health. No association was found between specific psychosocial work characteristics nor personal traits and hypersensitivity to electricity. We present skin and neurovegetative symptom indices. Results indicate that skin, and not neurovegetative symptoms, characterize the syndrome, at least during the first years of illness. For characterization, we propose a set of dimensions, including triggering factors, behavior, and duration of symptoms.

Personal decontamination after exposure to stimulated liquid phase contaminants: functional assessment of a new unit.

OBJECTIVE: To evaluate the efficacy of a decontamination station following exposure of volunteers to liquids with physical characteristics comparable to sarin and mustard gas. DESIGN: Twenty-four volunteers participated in the experiment which was performed with all staff wearing personal protective equipment including respiratory protection. The clothes, skin, and hair of the volunteers were contaminated with the simulated liquid phase contaminants, ethyl lactate and methyl salicylate. Sulphur hexafluoride gas was used to confirm the ventilation efficacy. Decontamination followed guidelines using a two-stage procedure. In the first chamber, all volunteers received a 3-minute shower with water at 30 degrees C, and their clothes but not their respiratory masks were removed. In the second, they were twice washed thoroughly with soap and water. After decontamination, the volunteers entered a third chamber for first aid measures. RESULTS: The air concentration of sulphur hexafluoride was reduced by 1:10,000 between the first and the third chambers. Ethyl lactate and methyl salicylate were measured in low concentrations in the third chamber. The capacity was 16 volunteers per hour with two-thirds on stretchers. After self-decontamination of the staff, the concentration of ethyl lactate increased significantly in the third chamber, consistent with residual ethyl lactate adsorbed by their underwear. This observation revealed a deficiency in the guidelines for self-decontamination. CONCLUSION: The capacity of the decontamination unit was found to be 16 volunteers per hour. The ventilation system and guidelines of the decontamination unit were demonstrated to be effective under the conditions examined. The self-decontamination of the staff was not optimal.

Violence toward health care workers. Prevalence and incidence at a large, regional hospital in Sweden.

The aim of this study was to establish data for career prevalence and 1 year incidence of work-place violence for major categories of health care workers. Three consecutive work environment questionnaire studies at a large Swedish hospital provided the basis for the study. Prevalence and incidence rates of violence were age and gender adjusted to the Swedish working population. Prevalence of violence in the study population was compared to data from a national sample of Swedish registered nurses. Incidence of violence in each professional group was compared to that of the largest group of hospital employees, registered nurses. Standardized prevalence ratios for violence were significantly higher for all nursing personnel and physicians, and were highest for practical nurses (1.56). Standardized incidence rates ranged from 18/100 person years for physicians to 31/100 person years for practical nurses. The relative risk for violence at work over a 1 year period was significantly higher only for practical nurses (1.59) as compared to registered nurses. Nursing personnel and physicians were at considerable risk for workplace violence in the course of their careers. One year incidence rates were highest for practical nurses.

Psychological patterns in patients with coronary heart disease, chronic pain and respiratory disorder.

Patients with coronary heart disease (CHD), chronic pain and respiratory disorder were investigated for different patterns of psychological factors. Several psychological factors were measured: depression (using Beck's 'BDI'), anxiety (using Spielberger's 'STAI'), anger (Spielberger's 'AX'), and cynicism (Greenglass & Julkunen's 'CD'). The special psychological pattern in patients with CHD was characterized by an increase in suppressed anger, overall experienced anger, and cynicism. Patients with chronic pain did not show any comparable pattern of elevated psychological factors. The pattern in patients with respiratory disorder was characterized by increased cynicism and, in women, also clinical depression.

Hospital Anxiety and Depression Scale (HAD): some psychometric data for a Swedish sample.

The Hospital Anxiety and Depression Scale (HAD) was evaluated in a Swedish population sample. The purpose of the study was to compare the HAD with the Beck Depression Inventory (BDI) and Spielberger's State Trait Anxiety Inventory (STAI). A secondary aim was to examine the factor structure of the HAD. The results indicated that the factor structure was quite strong, consistently showing two factors in the whole sample as well as in different subsamples. The correlations between the total HAD scale and BDI and STAI, respectively, were stronger than those obtained using the different subscales of the HAD (the anxiety and depression subscales). As expected, there was also a stronger correlation between the HAD and the non-physical items of the BDI. It was somewhat surprising that the factor analyses were consistently extracting two factors, 'depression' and 'anxiety', while on the other hand both BDI and STAI tended to correlate more strongly with the total HAD score than with the specific depression and anxiety HAD subscales. Nevertheless, the HAD appeared to be (as was indeed originally intended) a useful clinical indicator of the possibility of depression and clinical anxiety.

Stress and sensitization in children: a controlled prospective psychophysiological study of children exposed to international relocation.

This controlled prospective study investigated the development of sensitization as a result of international relocation in children, using the analyzing system Phadiatop. The effects of climate and predisposition to allergy were also measured. Children were examined prior to and during their first year of living abroad. A control group living at home was also examined during the same period. Participants answered a questionnaire before and after 1 year abroad, and blood samples were collected to determine sensitization. Before going abroad, there were no significant differences in atopic sensitization between groups nor in other key variables. After 1 year abroad, the proportion of children showing sensitization had increased significantly as compared with the control group at home. The exposed group reported an increase in skin symptoms during the year abroad. This study suggests that unidentified factors associated with foreign relocation increase the risk of sensitization in predisposed children. Stress might be one factor.

Exposure to mercury vapor and impact on health in the dental profession in Sweden.

Possible adverse effects of mercury exposure in dentistry have been discussed in several studies. The objective of the present study was to carry out detailed measurements of mercury exposure in the dental profession in Sweden, and to search for adverse health effects from such exposure. We examined 22 dentists and 22 dental nurses, working in teams, at six Swedish dental clinics. Measurements of air mercury, performed with personal, active air samplers, showed a median air Hg of 1.8 micrograms/m3 for the dentists, and 2.1 micrograms/m3 for the dental nurses. Spot measurements with a direct reading instrument displayed temporarily elevated air Hg, especially during the preparation and application of amalgam. The average concentration of mercury in whole blood (B-Hg) was 18 nmol/L, in plasma (P-Hg) 5.1 nmol/L, and in urine (U-Hg) 3.0 nmol/mmol creatinine. Possible effects on the central nervous system (CNS) were registered with three questionnaires: Q16, Eysenck Personality Inventory (EPI), and the Profile of Mood Scales (POMS). In the Q16, the number of symptoms was statistically significantly higher in the dentistry group compared with an age- and gender-matched control group (n = 44). The urinary excretion of albumin and urinary activity of the tubular enzyme N-acetyl-beta-glucose-aminidase (NAG) did not differ between the two groups. The results confirm that exposure to mercury in the dental profession in Sweden is low. The air Hg levels were mainly influenced by the method of amalgam preparation and inserting, and by the method of air evacuation during drilling and polishing.

Psychomotor development at 10 months as related to neonatal health status: the Stockholm Neonatal Project.

The psychomotor development of 171 preterm very-low-birthweight (VLBW) infants (birthweight < or = 1500 g) at 10 months of corrected age was assessed by the Griffiths' Mental Developmental Scale. The developmental score was related to the prenatal and obstetric risk factors and to the neonatal health status of each infant. These results, in turn, were compared to findings for a reference group of full-term infants. This analysis revealed that prolonged ventilator treatment, patent ductus arteriosus, bronchopulmonary dysplasia, brain haemorrhage with ventricle dilatation, white matter lesions, low birthweight and low gestational age influenced psychomotor development in an unfavourable manner. Multiple regression analysis confirmed most of these correlations. Preterm birth per se (when children with risk factors were excluded) in general had no significant effect on psychomotor development. However, the early development of preterm infants with several neonatal risk factors was adversely affected.

The Arabidopsis homeobox gene ATHB-7 is induced by water deficit and by abscisic acid.

Homeodomain-leucine zipper (HD-Zip) proteins are putative transcription factors encoded by a class of recently discovered homeobox genes as yet found only in plants. This paper reports on the characterization of one of these genes, ATHB-7, in Arabidopsis thaliana. ATHB-7 transcripts were present in all organs of the plant at low levels, but expression was induced several-fold by water deficit, osmotic stress as well as by exogenous treatment with abscisic acid (ABA), a response being detectable at 10(-8) M and reaching a maximum at 10(-6) M ABA. The ATHB-7 transcript was detected within 30 min after treatment with ABA and the transcript level was rapidly reduced after removal of the hormone. The induction of ATHB-7 was shown to be mediated strictly via ABA, since no induction of ATHB-7 was detectable in the ABA-deficient mutant aba-3 subjected to drought treatment. Induction levels in two ABA-insensitive mutants abi2 and abi3 were similar to the wild-type response. In the abi1 mutant, however, induction was impaired as 100-fold higher concentrations of ABA were required for a maximum induction as compared with wild-type. In this mutant the ATHB-7 response was reduced also after drought and osmotic stress treatments. These results indicate that ATHB-7 is transcriptionally regulated in an ABA-dependent manner and may act in a signal transduction pathway which mediates a drought response and also includes ABI1.