The role of medical illustration in the evolution of transsphenoidal pituitary surgery.

Medical illustration played a crucial, yet often overlooked, role in the evolution of pituitary surgery. From the late 1800s to the present, many preeminent surgeons, in partnership with their surgical illustrator collaborators, developed and then shifted the paradigm of pituitary surgery, from an open procedure with high mortality and morbidity, to an endonasal approach with high success rates that is widely utilized today. This work aims to highlight the role of surgical illustrators as partners to their physician colleagues, creating artistically accessible road maps that shaped the development of the transsphenoidal approach.

The Mayo, Cushing, and Osler Influence on A. L. Rhoton: A Historical Vignette of the Interconnectedness Between Highly Influential Neurosurgery Leaders over 100 Years.

The careers of the Mayo brothers, Harvey Cushing, and Sir William Osler greatly shaped medical and surgical practice in the late 19th century and early 20th century and created a legacy to influence decades of physicians to follow. Additionally, these individuals were instrumental in the founding of neurosurgery as a distinct surgical specialty. Alongside these great men, Dr. Albert L. Rhoton Jr., revolutionized neurosurgical practice through his study of neuroanatomy and development of microsurgical technique in the second half of the 20th century. This review of the interactions and relationships between the Mayo brothers, Cushing, and Osler and their influences on Rhoton highlights the 100-year-long interconnectedness shared between these giants in the history of neurosurgery.

Effective population size of Culex quinquefasciatus under insecticide-based vector management and following Hurricane Harvey in Harris County, Texas.

Introduction: Culex quinquefasciatus is a mosquito species of significant public health importance due to its ability to transmit multiple pathogens that can cause mosquito-borne diseases, such as West Nile fever and St. Louis encephalitis. In Harris County, Texas, Cx. quinquefasciatus is a common vector species and is subjected to insecticide-based management by the Harris County Public Health Department. However, insecticide resistance in mosquitoes has increased rapidly worldwide and raises concerns about maintaining the effectiveness of vector control approaches. This concern is highly relevant in Texas, with its humid subtropical climate along the Gulf Coast that provides suitable habitat for Cx. quinquefasciatus and other mosquito species that are known disease vectors. Therefore, there is an urgent and ongoing need to monitor the effectiveness of current vector control programs. Methods: In this study, we evaluated the impact of vector control approaches by estimating the effective population size of Cx. quinquefasciatus in Harris County. We applied Approximate Bayesian Computation to microsatellite data to estimate effective population size. We collected Cx. quinquefasciatus samples from two mosquito control operation areas; 415 and 802, during routine vector monitoring in 2016 and 2017. No county mosquito control operations were applied at area 415 in 2016 and 2017, whereas extensive adulticide spraying operations were in effect at area 802 during the summer of 2016. We collected data for eighteen microsatellite markers for 713 and 723 mosquitoes at eight timepoints from 2016 to 2017 in areas 415 and 802, respectively. We also investigated the impact of Hurricane Harvey's landfall in the Houston area in August of 2017 on Cx. quinquefasciatus population fluctuation. Results: We found that the bottleneck scenario was the most probable historical scenario describing the impact of the winter season at area 415 and area 802, with the highest posterior probability of 0.9167 and 0.4966, respectively. We also detected an expansion event following Hurricane Harvey at area 802, showing a 3.03-fold increase in 2017. Discussion: Although we did not detect significant effects of vector control interventions, we found considerable influences of the winter season and a major hurricane on the effective population size of Cx. quinquefasciatus. The fluctuations in effective population size in both areas showed a significant seasonal pattern. Additionally, the significant population expansion following Hurricane Harvey in 2017 supports the necessity for post-hurricane vector-control interventions.

Harvey and Gurvir's Law: The Need for Accurate Information Balanced Against Avoiding Unnecessary Restrictions on Autonomous Decision Making.

Decision making during reproduction is complex for a variety of medical and social reasons. Anyone who has had a conversation with a family member about the "best time" to have a baby can attest to this - there is no "best time" or "best way." Multiple pressures from any number of sources combine in a minefield of hazards made ever more complicated by restrictive laws in the US. Add to this a screening result of potential chromosomal aneuploidy and decision making becomes ever more complex. Societal stigma and lack of adequate and accurate information during counseling certainly plays a role in the high number of terminations in the setting of diagnosed chromosomal aneuploidy, yet other factors also push families in this direction including medical considerations and the abysmal lack of social support programs.

The AANS Harvey Cushing Medal: a demographic and academic analysis of its recipients.

Background: The Harvey Cushing Medal, awarded by the American Association of Neurological Surgeons, is the premier accolade in neurosurgery. The study's purpose was to examine the qualities and accomplishments of previous winners, emphasizing potential selection biases, with the aim to promote social justice and guide young neurosurgeons in their career paths. Results: Predominantly, recipients graduated from top-ranked United States News and World Report institutions and specialized in cerebrovascular and neuro-oncologic/skull base neurosurgery. A significant proportion held roles as department or division chairs and led neurosurgical organizations. All awardees were male, and there was a notable trend of increasing publication counts among more recent recipients. Conclusions: Commonalities among Harvey Cushing Medal winners include graduating from top institutions, holding significant leadership roles, and having an extensive publication history. However, the absence of female and underrepresented minority awardees underscores an urgent need for greater diversity in the selection process.

Lessons from the life of William Harvey.

William Harvey (1578-1658) discovered that blood flows in a circle and described this new finding in a short book in 1628. He had superb educational opportunities but also faced great difficulties, which he met with personal and professional resilience. A study of his life is worthwhile. Presented here are 11 lessons drawn from Harvey's life and legacy.

Social support and community embeddedness protect against post-disaster depression among immigrants: a Vietnamese American case study.

Immigrants often face increased vulnerabilities to disaster-related poor health and recovery, compared to mainstream populations. Little is known about Hurricane Harvey's impacts among the storm affected area's large Vietnamese American population. Our study documented diverse psychological experiences and recovery challenges 1 year post-storm among a sample of 120 Vietnamese Americans residing in the Houston, Texas area. Using linear regression modeling, we examined the association between social support and depressive symptom development among these storm-affected Vietnamese Americans. Social support encapsulating both social embeddedness and perceived support was measured by the Louisville Social Support Scale and depressive symptom development was measured by 18 items that assessed emotional distress. These items included loss of appetite, loss of concentration, exposure to persistent pain, and the exhibition of hopelessness, tiredness, sadness, frustration, discouragement, desperation, exhaustion, disgraced, anger, and craziness. We found adverse post-disaster health outcomes, as well as potential avenues to mitigate them, that should be taken into consideration in the design and implementation of inclusive disaster programs. A high level of social support lowered depressive symptomology among Vietnamese Americans post-Hurricane Harvey, even when accounting for Hurricane Harvey-related home damages and injuries/illness. The negative association between social support and depressive symptom development remained after accounting for both post-storm self-rated mental and physical health. Our results suggested that public health practitioners and emergency management entities should prioritize social support resources to foster mental well-being after hurricanes among Vietnamese Americans as future hurricanes are expected to be stronger and more prevalent along the United States Gulf Coast.

Meningioma: A Biography-Tumor Forever Tied to the Origins and "Soul of Neurosurgery".

Meningiomas are neoplasms derived from the arachnoid cap cells of the leptomeninges and are the most common intracranial tumor. In the present historical vignette, the evolution of the management and diagnosis of meningioma is described. We begin with studies of skulls from the prehistoric record, such as the Steinheim skull, which demonstrate morphologic changes (e.g., hyperostosis) now known to occur with meningioma growth. We then continue with the earliest formal descriptions of meningiomas, including that by Platter, who published the first report of meningioma, along with early histopathologic descriptions by Cushing, who divined the cytological origins of the tumor and was the first to use the term meningioma. We conclude with a description of current management of meningiomas and potential avenues for further discovery. This article is effectively a lifetime biography of a tumor known and loved by neurosurgeons, the simple and yet complex meningioma.

The relationship between the severity of inflammatory bowel diseases and expirium air carbon monoxide levels.

INTRODUCTION: We investigated the relationship between expirium air carbon monoxide (E-CO) levels and disease severity in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: After their first follow-ups, the E-CO levels of 162 patients with UC and 100 with CD were measured for four consecutive weeks. Blood samples were collected from all the patients, and their clinical severity was determined 1 month after their initial presentation. The clinical severity of CD was determined using the Harvey Bradshaw index (HBI), while the patients with UC completed the SEO clinical activity index (SEOI). The relationships between the disease severity and the means of these four E-CO readings were then compared. RESULTS: The mean age of the participants was 42.28 ± 14.9 years, and 158 (60.3%) were men. In addition, 27.2% of the UC group and 44% of the CD group were smokers. The mean SEOI score was 145.7 ± 42.0 (min = 90, max = 227), and the mean HBI score was 5.75 ± 3.3 (min = 1, max = 15). Increased CO ppm (OR = -9.047 to 7.654 95% CI) and the number of cigarettes smoked per day (OR = -0.161 to 1.157 95% CI) emerged as independent risk factors for lower SEO scores in the linear regression models (p < 0.001), while the number of cigarettes smoked per day (OR = 0.271 to 1.182% 95 CI) was a risk factor for higher HBI scores (p = 0.022). CONCLUSION: UC severity decreased with higher E-CO levels and the mean number of cigarettes smoked, while CD severity increased in line with the mean number of cigarettes smoked.

Adverse Health Outcomes Following Hurricane Harvey: A Comparison of Remotely-Sensed and Self-Reported Flood Exposure Estimates.

Remotely sensed inundation may help to rapidly identify areas in need of aid during and following floods. Here we evaluate the utility of daily remotely sensed flood inundation measures and estimate their congruence with self-reported home flooding and health outcomes collected via the Texas Flood Registry (TFR) following Hurricane Harvey. Daily flood inundation for 14 days following the landfall of Hurricane Harvey was acquired from FloodScan. Flood exposure, including number of days flooded and flood depth was assigned to geocoded home addresses of TFR respondents (N = 18,920 from 47 counties). Discordance between remotely-sensed flooding and self-reported home flooding was measured. Modified Poisson regression models were implemented to estimate risk ratios (RRs) for adverse health outcomes following flood exposure, controlling for potential individual level confounders. Respondents whose home was in a flooded area based on remotely-sensed data were more likely to report injury (RR = 1.5, 95% CI: 1.27-1.77), concentration problems (1.36, 95% CI: 1.25-1.49), skin rash (1.31, 95% CI: 1.15-1.48), illness (1.29, 95% CI: 1.17-1.43), headaches (1.09, 95% CI: 1.03-1.16), and runny nose (1.07, 95% CI: 1.03-1.11) compared to respondents whose home was not flooded. Effect sizes were larger when exposure was estimated using respondent-reported home flooding. Near-real time remote sensing-based flood products may help to prioritize areas in need of assistance when on the ground measures are not accessible.

Factors Associated With Poor Health Outcomes Among Vietnamese Americans After Hurricane Harvey, Houston, Texas, 2018-2019.

OBJECTIVE: Immigrants typically experience poor health outcomes after disasters but are often excluded in disaster studies. We assessed physical and mental health outcomes among Houston-area Vietnamese American residents after Hurricane Harvey and hurricane-related characteristics associated with poor health outcomes. METHODS: We conducted in-person structured surveys among 120 Vietnamese Americans from November 2018 through February 2019. We used the physical and mental component scores of the 12-Item Short-Form Health Survey to assess health outcomes. We used descriptive statistics for health outcomes and hurricane-related effects and examined the associations between hurricane-related characteristics and health outcomes. RESULTS: Overall mean (95% CI) physical and mental component scores were 39.8 (29.7-49.9) and 32.6 (27.6-37.6), respectively. The odds of poor physical health poststorm were significantly higher among participants reporting ≥5 versus <5 depressive symptoms (odds ratio [OR] = 3.04; 95% CI, 1.11-8.29; P = .03) and significantly lower among participants with versus without health insurance (OR = 0.25; 95% CI, 0.09-0.71; P = .01). The odds of experiencing poor mental health more than a year after the hurricane were significantly higher among those sustaining versus not sustaining a serious injury/illness because of the hurricane (OR = 3.34; 95% CI, 1.12-9.94; P = .03) and among those who were married/partnered versus not married/partnered (OR = 4.16; 95% CI, 1.32-13.07; P = .02). Receiving versus not receiving free health care services after the hurricane and having high versus low levels of acculturation protected against poor mental health (P < .05 for both). CONCLUSIONS: Our findings highlight the inequalities of postdisaster health outcomes in this immigrant population and emphasize the need for improved disaster recovery programs that account for these factors.

The Pioneer Neuropharmacologist Alfred Fröhlich (1871-1953) and the Origins of Neuroendocrinology: A Sesquicentennial Remembrance.

The birth of neuroendocrinology as a scientific discipline is traced back to 1900-1901, when Joseph Babinski, Alfred Fröhlich, and Harvey Cushing independently identified adiposogenital dystrophy (Fröhlich syndrome), and related gonadal underdevelopment and obesity to a tumor near the pituitary gland. This discovery prompted decades of research into the brain mechanisms responsible for the control of peripheral metabolism and endocrine functions. On the occasion of the 150th anniversary of Fröhlich's birth, this study traces the origins of his intellectual formation and his association with renowned contemporaries in Austria, England, Italy, and finally Cincinnati, Ohio, where he sought refuge after Austria's annexation by Nazi Germany. Fröhlich interacted with seminal figures in biomedicine, including Lothar von Frankl-Hochwart, Hans Horst Meyer, Ernst Peter Pick, Harvey Cushing, John Newport Langley, and the Nobel laureates Charles Scott Sherrington and Otto Loewi. Alfred Fröhlich, one of the 20th century's most emblematic physicians, left his mark on neurophysiology and neuropharmacology with important works, and published authoritative manuals of drug dispensing and clinical therapy. He confronted the calamities of two World Wars with remarkable resilience like many of his Viennese colleagues who, overcoming the constraints of National Socialism, settled overseas to fulfil their calling as physicians, researchers, and teachers.

"You gotta give them hope": A structural psychobiography of Harvey Milk (1930-1978).

OBJECTIVE: In this psychobiographical study, we examined the life and times of social change agent Harvey Milk, one of the first openly gay public officials in the United States. Milk is remembered as a gay hero who fought for the rights of marginalized people, often by invoking the importance of hope. Milk was assassinated less than 1 year after his election. METHOD: We adopt a structural psychobiographical approach, foregrounding social, cultural, political, and historical forces that intersect with personal factors to explain Milk's ascension to the status of social change agent. RESULTS: This psychobiography tells the story of a man not destined to become a social change agent but who became one anyway because of shifting tides in the political climate of San Francisco in the 1970s, because of a series of catalytic events that started him down this path, because of a history of persecution as a gay Jew, and because of his enduring need for a stage upon which he could express his generative concern. CONCLUSIONS: Our analysis raises questions about the story that "belongs" to the agent of social change, and the story that "belongs" to the rest of us, as we remember him.

Agreement between patients and physicians on scores of inflammatory bowel disease activity and burden assessed on a telemonitoring platform.

BACKGROUND AND AIMS: Telemonitoring is increasingly used in the management of IBD patients. We investigated the agreement between patients and physicians on scores of disease activity and burden. METHODS: Consecutive outpatients at one IBD clinic were recruited between February and December 2021. Enrolled patients completed a questionnaire for disease activity (Harvey-Bradshaw Index [HBI] for Crohn's disease or Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis) and a test of disease burden (Pictorial Representation of Illness and Self Measure [PRISM]). They did the tests within 5 days of an outpatient visit, working independently on IBD Tool, a new web-based telemonitoring application. Concomitantly, the senior and junior physicians who examined them completed the same tests. The agreement was tested for every pair of scores. RESULTS: Five hundred and sixty patients (289 Crohn's disease; 271 ulcerative colitis) completed disease questionnaires on IBD Tool (in total, 742 times). By Spearman's correlation, the agreement was substantial both for HBI (rho 0.685-0.837) and SCCAI (rho 0.694-0.888) for comparisons between patients, junior and senior physicians. The agreement was moderate-to-substantial for PRISM (rho 0.406-0.725) for the same comparisons. The correlation between disease activity (HBI/SCCAI) and PRISM scores was substantial for senior (rho 0.757-0.788) or junior (rho 0.746-0.753) physicians and moderate for patients (rho 0.458-0.486). The median PRISM score difference was 2.3-1.6 points lower between patients and senior-junior physicians. CONCLUSION: Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease impact. The inclusion of disease burden scoring in telemonitoring platforms provides important information for the management of IBD patients.Study highlightsWhat IS known•Continuous response to treatments and patient-reported outcomes became an essential goal for IBD patient management.•The use of tele-monitoring and eHealth technologies allows for regular disease assessments and for managing more efficiently IBD patients; disease questionnaires and tests are key to support eHealth tools.What is new here•Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease burden, while agreement among junior and senior physicians was substantial for both.•PRISM performs as well for ulcerative colitis as for Crohn's patients.•The inclusion of disease burden tests might add to eHealth platforms valuable information, complemental to disease activity questionnaires.

Sir William Osler's fatal trip to Scotland: "Mrs M" and the University Grants Committee.

On 23 September 1919, Sir William Osler, after a telephone call from his friend Dyson Perrins, went to Glasgow where he saw a 40-year-old woman, Bethia Fulton Martin, in consultation with three local physicians. Osler called it "one of those remarkable Erythema cases (all sorts of skin lesions and three months on and off consolidation of both lower lobes)." Mrs Martin died 114 days later; her death certificate listed "angioneurotic oedema with chronic nephritis" and "tuberculous enlargement of the mediastinal lymph nodes." Osler died 18 days before Mrs Martin of complications from a respiratory infection acquired on his way home from Scotland. We discuss factors that possibly prompted Osler to go to Scotland, including his role with the newly formed University Grants Committee, and the differential diagnosis of the case, which is mainly between systemic lupus erythematosus and Henoch-Schönlein purpura.

Does flooding get worse with subsiding land? Investigating the impacts of land subsidence on flood inundation from Hurricane Harvey.

As one of the most devastating tropical storms, 2017 Hurricane Harvey caused severe flooding and damage in Houston, Texas. Besides enormous rainfall amount, land subsidence might be another contributing factor to the Harvey flood. However, few studies have numerically quantified the evolvement of land subsidence over decades, largely due to the lack of reliable methods to realistically estimate land subsidence both continuously and at high spatial resolution. Therefore, this study aims to investigate retrospective changes of regional topology due to 117 years (1900 to 2017) of land subsidence and the consequent impacts on flood inundation. Based on continuous land subsidence, we conduct a series of simulations on the 2017 Hurricane Harvey in Brays Bayou, Texas using a hydrodynamic/hydraulic model. The results indicate that the overall change of flood depth caused by land subsidence is relatively minor with the flood water deepened by six centimeters per one meter of subsided land at the worst impacted location. The impact from land subsidence on flood depth exhibits strong nonlinearity in time, where effects from previous land subsidence hotspots could be altered by later continuing land subsidence. Spatially, changes in flood depth due to the land subsidence are not only heterogeneous but mixed with coexisting increased and reduced flood depths. The results of this study improve the understanding of the dynamic evolvement of flood inundation due to continuous land subsidence so that better planning can be initiated for sustainable urban development for coastal communities, which is imperative under ongoing climate change and sea level rise.

Determinants of exposure to endocrine disruptors following hurricane Harvey.

Hurricane Harvey was a category four storm that induced catastrophic flooding in the Houston metropolitan area. Following the hurricane there was increased concern regarding chemical exposures due to damage caused by flood waters and emergency excess emissions from industrial facilities. This study utilized personal passive samplers in the form of silicone wristbands in Houston, TX to both assess chemical exposure to endocrine disrupting chemicals (EDCs) immediately after the hurricane and determine participant characteristics associated with higher concentrations of exposure. Participants from the Houston-3H cohort (n = 172) wore a wristband for seven days and completed a questionnaire to determine various flood-related and demographic variables. Bivariate and multivariate analysis indicated that living in an area with a high Area Deprivation Index (ADI) (indicative of low socioeconomic status), identifying as Black/African American or Latino, and living in the Houston neighborhoods of Baytown and East Houston were associated with increased exposure to EDCs. These results provide evidence of racial/ethnic and socioeconomic injustices in exposure to EDCs in the Houston Metropolitan Area. Since the multiple regression models conducted did not fully explain exposure (0.047 < R2 < 0.34), more research is needed on the direct sources of EDCs within this area to create effective exposure mitigation strategies.

Correlation of endoscopic evaluation with laboratory indices and clinical disease activity in Crohn disease patients with different intestinal involvement / 中华消化内镜杂志

Objective:To investigate the correlations of endoscopic evaluation results with laboratory indices and clinical disease activity in Crohn disease (CD) patients with different intestinal involvement.Methods:Data of 147 patients diagnosed as having CD who visited the Department of Gastroenterology, Zhongnan Hospital of Wuhan University from July 1, 2017 to June 30, 2022 were collected retrospectively. According to the involvement of intestinal segment, patients were divided into three groups: the group with isolated small intestinal involvement ( n=55), the group with both small intestinal and large intestinal involvement ( n=48), and the group with isolated large intestinal involvement ( n=44). Correlations of endoscopic evaluation (based on CDEIS) with laboratory indices and clinical disease activity (based on Harvey-Bradshaw index) were analyzed. Results:C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) could be used for the prediction of endoscopic disease activity. The areas under curve (AUC) of receiver operator characteristic (ROC) were 0.677 (0.506-0.849) and 0.744 (0.597-0.890), respectively. In terms of determing clinical disease activity, clinical Harvey-Bradshaw index was consistent with endoscopic CDEIS score in 65.3% (96/147) patients, showing a low positive correlation ( r=0.260, P<0.05). In subgroup analysis for patients with isolated small intestinal involvement, CRP showed no predictive value for clinical disease activity [AUC (95% CI): 0.617 (0.461-0.773), P=0.148], while for endoscopic activity neither CRP nor ESR showed predictive value [AUC (95% CI): 0.537 (0.146-0.929), P=0.829; AUC (95% CI): 0.571 (0.153-0.990), P=0.680]. Furthermore, for patients with isolated small intestinal involvement and both small intestinal and large intestinal involvement, no correlation was found between clinical Harvey-Bradshaw index and endoscopic CDEIS score ( r=0.222, P=0.092; r=0.142, P=0.322). Conclusion:For CD patients with small intestinal involvement, especially isolated small intestinal involvement, laboratory indices and clinical disease activity cannot accurately reflect endoscopic disease activity. Great importance should be attached to evaluation of the extent and activity of intestinal lesions by endoscopy, especially enteroscopy.

A utopian idea: Cushing, Bailey, Penfield, and the National Institute of Neurological Diseases and Blindness.

Toward the end of the First World War, Harvey Cushing conceived of a National Institute of Neurology (NIN) that would integrate neurology, neurosurgery, psychiatry, and allied disciplines within a single institution. It would first be established for the care of American casualties in an existing military hospital in France, and then relocate to the United States. Cushing was unsuccessful in acquiring funding for this project despite appeals to the army and to the Carnegie and Rockefeller foundations. By 1920 the idea had faded from memory. In 1933 Wilder Penfield was successful in obtaining funding from the Rockefeller Foundation for the creation of the Montreal Neurological Institute (MNI). The MNI's faculty held full-time university appointments and they limited their practice to the institute, where their offices and clinics were housed, and to adjoining research laboratories in neuroanatomy, neurochemistry, neurophysiology, and neuropsychology, as Cushing had envisioned. In this paper the argument is made that although Cushing's plan for the NIN was premature, the success of the MNI proved its feasibility. In addition, the MNI's success in integrating clinical care and research within a single institution was a model for the National Institute of Neurological Diseases and Blindness and drove its first clinical research program.

Estimation of Lens Stray Light with Regard to the Incapacitation of Imaging Sensors-Part 2: Validation.

Recently, we developed a simple theoretical model for the estimation of the irradiance distribution at the focal plane of commercial off-the-shelf (COTS) camera lenses in case of laser illumination. The purpose of such a model is to predict the incapacitation of imaging sensors when irradiated by laser light. The model is based on closed-form equations that comprise mainly standard parameters of the laser dazzle scenario and those of the main devices involved (laser source, camera lens and imaging sensor). However, the model also includes three non-standard parameters, which describe the scattering of light within the camera lens. In previous work, we have performed measurements to derive these typically unknown scatter parameters for a collection of camera lenses of the Double-Gauss type. In this publication, we compare calculations based on our theoretical model and the measured scatter parameters with the outcome of stray light simulations performed with the optical design software FRED in order to validate the reliability of our theoretical model and of the derived scatter parameters.