Imaging Signs of May-Thurner Syndrome in Asymptomatic Patients: Computed Tomography Angiography Analysis of Kidney Donors.

BACKGROUND: The current study aimed to evaluate the distance between the right common iliac artery (RCIA) and lumbar vertebra in asymptomatic patients in order to determine whether such distance was statistically correlated with the left common iliac vein (LCIV) diameter (LCIVD) and to investigate if both measures were related to demographic characteristics and anthropometric data, such as sex, age, height, and body mass index (BMI). METHODS: In this descriptive and uncontrolled anatomic study, data from high-definition computed tomography (CT) angiography images of living kidney donors without a medical history of chronic venous insufficiency or past deep vein thrombosis (DVT) were analyzed. The RCIA crossed over the LCIV in 311 individuals, who were then included in this study. CT scans were reviewed to measure (1) the narrowest space between the RCIA and fifth lumbar vertebral body and (2) the LCIVD. Measures were subjected to normality tests and were divided according to the sex of the study population. Correlations of measures with age, BMI, and height were calculated. RESULTS: Of the 311 patients analyzed, 66.6% (n = 207) were female. The mean lumbar vertebral body-iliac artery distance (LVBIAD) was 7.2 mm, whereas the mean LCIVD was 8.5 mm; both were higher in men (P < 0.001). The statistical analysis of LVBIAD and LCIVD distributions revealed no normality pattern (P < 0.05). The analysis of the correlation between them showed a weak statistically significant relationship with age. A linear regression model considering the normality percentile interval indicated a strong positive correlation between LVBIAD and LCIVD (R2 = 0.884). CONCLUSIONS: The LVBIAD was <5 mm and <3 mm in 25% and 5% of asymptomatic individuals, respectively. The LCIVD correlated with the space between the RCIA and lumbar vertebra. The distance between the RCIA and lumbar vertebra and the LCIVD were higher in male subjects and older patients, but did not correlate with BMI and height.

EvoDesigner: Evolving Poster Layouts.

Frequently, one of the goals of Graphic Design (gd) is discovering disruptive visual solutions that stand out and attract people's attention. However, due to the increasing democratisation of gd, graphic designers tend to adopt design trends, leading to designs that many times lack innovative and catchy features. EvoDesigner is an evolutionary extension for Adobe InDesign that aims to aid gd processes by automatically evolving layout and style variations of given InDesign pages. The generated pages might be previously created and post-edited by designers, promoting co-creation. As an extension of the study EvoDesigner: Towards Aiding Creativity in Graphic Design, this article begins with a general introduction of EvoDesigner. Then, we review previous experiments on evolving pages towards the page balance of existing target posters. Furthermore, we present new experiments exploring the benefits of using grid systems to position and scale page items along with a user survey made to gather feedback about the impact of grid systems in the generated pages and showcase examples of artefacts created from the collaboration between designers and the system. The findings indicate that the presented techniques can be used to interpret current layouts in different manners, and suggest that grid systems may be a useful tool for promoting the automatic production of layouts with better organisation when compared to applying no organisational constraints. However, a conducted user survey indicates that, depending on the goals of the designers, more organised layouts might not always be synonymous with better results.

Surgical outcome of a post-traumatic dystonic foot: Case report and literature review.

Post-traumatic dystonia is an underrecognized condition that can present with bizarre symptoms after trauma, usually out of proportion to the trigger event. We describe the case of a 31-year-old man with a severe lower extremity deformity, gradually developed after minor trauma. An interdisciplinary treatment was tried without any improvement and surgery was performed as a rescue approach. Tibialis anterior tendon transfer and hindfoot triple arthrodesis were carried out, successfully achieving a plantigrade foot and a functional gait. Despite the scarce literature available about functional results of surgery in dystonic feet, we present a step-by-step comprehensive approach to this disorder. LEVEL OF CLINICAL EVIDENCE: 4.

Winning compensations: Adaptable gaming approach for upper limb rehabilitation sessions based on compensatory movements.

Recent research has been using automatic difficulty adjustment techniques as an effective channel to improve the quality of physical rehabilitation. Notably, these approaches often incorporate adaptation metrics such as emotions and performance. Nonetheless, compensatory movements, which hinder movement correctness and are considered as a core quality evaluation criterion of rehabilitation, have not been considered as an adaptation metric. Weighting how visual feedback interfaces increase patient engagement, we leverage an interactive system with a compensatory movements-based difficulty adjustment framework to enhance the upper-limb physical rehabilitation process. We conducted user tests with professionals (N = 15), which included observation sessions, co-design workshops, semi-structured interviews, and usability testing, to evaluate our prototype. Results showed that our interactive system achieved scores of perceived usability between 74 and 78.17, along with participants praising both the dynamic and manual customization of difficulty parameters. Our findings empower physical therapists and health professionals by reducing their burden on physical rehabilitation monitorization.

Laparoscopy with augmented reality adaptations.

One of the most promising applications of Optical See-Through Augmented Reality is minimally laparoscopic surgery, which currently suffers from problems such as surgeon discomfort and fatigue caused by looking at a display positioned outside the surgeon's visual field, made worse by the length of the procedure. This fatigue is especially felt on the surgeon's neck, as it is strained from adopting unnatural postures in order to visualise the laparoscopic video feed. Throughout this paper, we will present work in Augmented Reality, as well as developments in surgery and Augmented Reality applied to both surgery in general and laparoscopy in particular to address these issues. We applied user and task analysis methods to learn about practices performed in the operating room by observing surgeons in their working environment in order to understand, in detail, how they performed their tasks and achieved their intended goals. Drawing on observations and analysis of video recordings of laparoscopic surgeries, we identified relevant constraints and design requirements. Besides proposals to approach the ergonomic issues, we present a design and implementation of a multimodal interface to enhance the laparoscopic procedure. Our method makes it more comfortable for surgeons by allowing them to keep the laparoscopic video in their viewing area regardless of neck posture. Also, our interface makes it possible to access patient imaging data without interrupting the operation. It also makes it possible to communicate with team members through a pointing reticle. We evaluated how surgeons perceived the implemented prototype, in terms of usefulness and usability, via a think-aloud protocol to conduct qualitative evaluation sessions which we describe in detail in this paper. In addition to checking the advantages of the prototype as compared to traditional laparoscopic settings, we also conducted a System Usability Scale questionnaire for measuring its usability, and a NASA Task Load Index questionnaire to rate perceived workload and to assess the prototype effectiveness. Our results show that surgeons consider that our prototype can improve surgeon-to-surgeon communication using head pose as a means of pointing. Also, surgeons believe that our approach can afford a more comfortable posture throughout the surgery and enhance hand-eye coordination, as physicians no longer need to twist their necks to look at screens placed outside the field of operation.

Avoidable environmental disasters and infant health: Evidence from a mining dam collapse in Brazil.

We study the health consequences of one of the largest environmental disasters of the world mining industry, which largely stemmed from regulatory failure. Exploiting the timing and location of the Mariana mine tailings dam collapse in Brazil, we show that in utero exposure to the tragedy significantly reduced birth weight and increased infant mortality. The adverse effects were stronger for infants born to less educated and nonmarried mothers. These findings indicate that poorly enforced environmental regulation may have long-term welfare impacts on local communities.

Touchless interaction with medical images based on 3D hand cursors supported by single-foot input: A case study in dentistry.

Feet input can support mid-air hand gestures for touchless medical image manipulation to prevent unintended activations, especially in sterile contexts. However, foot interaction has yet to be investigated in dental settings. In this paper, we conducted a mixed methods research study with medical dentistry professionals. To this end, we developed a touchless medical image system in either sitting or standing configurations. Clinicians could use both hands as 3D cursors and a minimalist single-foot gesture vocabulary to activate manipulations. First, we performed a qualitative evaluation with 18 medical dentists to assess the utility and usability of our system. Second, we used quantitative methods to compare pedal foot-supported hand interaction and hands-only conditions next to 22 medical dentists. We expand on previous work by characterizing a range of potential limitations of foot-supported touchless 3D interaction in the dental domain. Our findings suggest that clinicians are open to use their foot for simple, fast and easy access to image data during surgical procedures, such as dental implant placement. Furthermore, 3D hand cursors, supported by foot gestures for activation events, were considered useful and easy to employ for medical image manipulation. Even though most clinicians preferred hands-only manipulation for pragmatic purposes, feet-supported interaction was found to provide more precise control and, most importantly, to decrease the number of unintended activations during manipulation. Finally, we provide design considerations for future work exploring foot-supported touchless interfaces for sterile settings in Dental Medicine, regarding: interaction design, foot input devices, the learning process and camera occlusions.

Development of a Puncture Technique for Implanting Temporary Vascular Shunts in a Porcine Model.

BACKGROUND: Temporary vascular shunts (TVSs) are an effective tool for rapidly restoring blood flow to a limb or organ that has experienced vascular injury and ischemia and for which revascularization is not an immediate option. Usually, through an opening in the skin, the TVS is positioned within the proximal and distal stumps of the injured vessel, restoring perfusion and stopping the ischemia. The aim of this study is to compare standard TVS technique and a developed puncture technique for implanting TVS and to evaluate the utility and feasibility of this protocol after arterial lesions, in pigs. METHODS: Vascular injuries were inflicted in both hind limbs of 30 pigs, and vascular interventions were performed, using standard and puncture TVS. Because each pig was implanted with both types of TVSs, it was possible to simultaneously monitor, analyze, and compare parameters such as, the mean arterial pressure (MAP, in mm Hg), blood flow (mL/min), and insertion times, in the same animal. RESULTS: It was observed that the MAP in the limbs recovered and approached systemic MAP, in 100% of the experiments, in both groups. Analysis of the blood flow data showed that this parameter was significantly reduced in the puncture TVS group (110.36 ± 9.99 mL/min vs. 153.20 ± 18.57 mL/min, P = 0.001). On the other hand, the insertion time for the standard TVS was significantly greater than that of the puncture shunt (15.32 ± 3.08 min vs. 10.37 ± 1.7 min, P = 0.001). Furthermore, it was found that the primary and secondary patency and complication rates were similar for both TVS types. CONCLUSION: Thus, given the adequate MAP recovery and reduction in implantation time observed in this experimental and in an animal model study, the use of the puncture TVS technique is effective and feasible.

Development of blueberry liquor: influence of distillate, sweetener and fruit quantity.

BACKGROUND: In this work different formulations of blueberry liquor were tested and characterised based on their physico-chemical and sensory characteristics. RESULTS: Three factors were evaluated: the distillate used to produce the liquor (wine spirit or grape marc spirit); the sweetener (white sugar or honey) and the fruit quantity (two doses). For each liquor, pH, total acidity, dry soluble solids content, dry extract, alcoholic strength, reducing sugars, colour intensity, methanol content, acetaldehyde and fusel alcohols were determined. Sensory tests were carried out with a trained panel. CONCLUSION: The three factors studied significantly influenced the physico-chemical features of the liquors, being the quantity of fruit the most discriminating factor, except for the volatile compounds which were mainly influenced by the distillate. As regards the sensory analysis, it was found that the most appreciated liquor was that prepared with wine spirit, sugar and a lower dose of blueberry, and the less appreciated formulation was the one made with grape marc spirit, honey and a lower quantity of blueberry. © 2017 Society of Chemical Industry.

Addressing geographic access barriers to emergency care services: a national ecologic study of hospitals in Brazil.

BACKGROUND: Unequal distribution of emergency care services is a critical barrier to be overcome to assure access to emergency and surgical care. Considering this context it was objective of the present work analyze geographic access barriers to emergency care services in Brazil. A secondary aim of the study is to define possible roles to be assumed by small hospitals in the Brazilian healthcare network to overcome geographic access challenges. METHODS: The present work can be classified as a cross-sectional ecological study. To carry out the present study, data of all 5843 Brazilian hospitals were categorized among high complexity centers and small hospitals. The geographical access barriers were identified through the use of two-step floating catchment area method. Once concluded the previous step an evaluation using the Getis-Ord-Gi method was performed to identify spatial clusters of municipalities with limited access to high complexity centers but well covered by well-equipped small hospitals. RESULTS: The analysis of accessibility index of high complexity centers highlighted large portions of the country with nearly zero hospital beds by inhabitant. In contrast, it was possible observe a group of 1595 municipalities with high accessibility to small hospitals, simultaneously with a low coverage of high complexity centers. Among the 1595 municipalities with good accessibility to small hospitals, 74% (1183) were covered by small hospitals with at least 60% of minimum emergency service requirements. The spatial clusters analysis aggregated 589 municipalities with high values related to minimum emergency service requirements. Small hospitals in these 589 cities could promote the equity in access to emergency services benefiting more than eight million people. CONCLUSIONS: There is a spatial disequilibrium within the country with prominent gaps in the health care network for emergency services. Taking this challenge into consideration, small hospitals could be a possible solution and foster equity in access to emergency and surgical care. However more investments in are necessary to improve small hospitals capabilities to fill this gap.

On the utility of 3D hand cursors to explore medical volume datasets with a touchless interface.

Analyzing medical volume datasets requires interactive visualization so that users can extract anatomo-physiological information in real-time. Conventional volume rendering systems rely on 2D input devices, such as mice and keyboards, which are known to hamper 3D analysis as users often struggle to obtain the desired orientation that is only achieved after several attempts. In this paper, we address which 3D analysis tools are better performed with 3D hand cursors operating on a touchless interface comparatively to a 2D input devices running on a conventional WIMP interface. The main goals of this paper are to explore the capabilities of (simple) hand gestures to facilitate sterile manipulation of 3D medical data on a touchless interface, without resorting on wearables, and to evaluate the surgical feasibility of the proposed interface next to senior surgeons (N=5) and interns (N=2). To this end, we developed a touchless interface controlled via hand gestures and body postures to rapidly rotate and position medical volume images in three-dimensions, where each hand acts as an interactive 3D cursor. User studies were conducted with laypeople, while informal evaluation sessions were carried with senior surgeons, radiologists and professional biomedical engineers. Results demonstrate its usability as the proposed touchless interface improves spatial awareness and a more fluent interaction with the 3D volume than with traditional 2D input devices, as it requires lesser number of attempts to achieve the desired orientation by avoiding the composition of several cumulative rotations, which is typically necessary in WIMP interfaces. However, tasks requiring precision such as clipping plane visualization and tagging are best performed with mouse-based systems due to noise, incorrect gestures detection and problems in skeleton tracking that need to be addressed before tests in real medical environments might be performed.

Development of a large peptoid-DOTA combinatorial library.

Conventional one-bead one-compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built-in imaging component for a certain target is a daunting task, and structure-based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on-bead library of 153,600 Peptoid-DOTA compounds in which the peptoids are the target-recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6-mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on-bead development of large peptidomimetic-DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 673-684, 2016.

Shape Analysis of the Femoral Head: A Comparative Study Between Spherical, (Super)Ellipsoidal, and (Super)Ovoidal Shapes.

In this work, MacConaill's classification that the articular surface of the femoral head is better represented by ovoidal shapes rather than purely spherical shapes is computationally tested. To test MacConaill's classification, a surface fitting framework was developed to fit spheres, ellipsoids, superellipsoids, ovoids, and superovoids to computed tomography (CT) data of the femoral proximal epiphysis. The framework includes several image processing and computational geometry techniques, such as active contour segmentation and mesh smoothing, where implicit surface fitting is performed with genetic algorithms. By comparing the surface fitting error statistics, the results indicate that (super)ovoids fit femoral articular surfaces better than spherical or (super)ellipsoidal shapes.

Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Phagia: A Case Report and Review of Literature of a Rare Disease Manifestation.

Diffuse idiopathic skeletal hyperostosis (DISH), also called Forestier disease, is a clinical entity characterized by ossification of the anterolateral ligaments of the spine. DISH is more commonly diagnosed in older males, with an estimated prevalence of 42% in patients older than 65 years. As the disease affects predominantly the thoracic spine, dysphagia is a rare presentation of this entity observed in only 0.6-1.0% of the cases. We present a clinical case of an 84-year-old male with complaints of progressive dysphagia and foreign body sensation within one year of evolution. Computed tomography imaging revealed an anterior C4-C5 osteophyte compressing the posterior hypopharyngeal wall. Flexible endoscopy revealed a deformed and stenotic hypopharynx. The patient underwent surgical treatment with anterior cervical osteophyte resection using the Smith-Robinson approach. The patient showed significant improvement in preoperative symptoms, and no recurrence was detected at six months of follow-up. We also aim to discuss the clinical and radiological characteristics of the disease, as well as the crucial steps for a correct diagnosis and treatment of this rare disease.

Effects of forage quality and particle size on feed intake and ruminoreticulum content of goats.

The aim was to evaluate the effect of particle size and hay quality on feed intake, granulometric profile, and composition of the ruminoreticulum content in goats. We used 54 Alpine bucks in a completely randomized design with a factorial arrangement of 3 × 3. Treatments were a combination of Bermuda grass hay (Cynodon dactylon) with three quality levels: high (35 days), medium (50 days), and low (65 d) harvested at regrowth times. Were evaluated three particle sizes: small (16% ≥4.76 mm), medium (48% ≥4.76 mm), and large (75% ≥4.76 mm), which accounted for 66%, 75%, and 94% of physically effective fiber, respectively. Samples of offered diet, intake, and ruminoreticulum content were used to generate the granulometric profile. The offered diet, intake, and ruminoreticulum content presented different granulometric profiles regarding hay quality and particle size. Dry matter intake (DMI) and neutral detergent fiber intake (NDFI) increased (P < 0.05) when low-quality hay and large particles were offered. However, when particle size in low-quality hay was reduced, DMI and NDF decreased (P < 0.05). When analyzing the ruminoreticulum content (DM, NDF, peNDF, and indigestible DM), we did not observe any effect (P > 0.05) of hay quality or particle size on the variables. Thus, reducing hay quality and increasing particle size increase dry matter and fiber intake, presenting an interaction between forage quality and particle size. Forage quality and particle size promote intense selective behavior and chewing, which leads to a homogeneous content of particle profile in ruminoreticulum and a uniform average retention time.

Skin deformation analysis for pre-operative planning of DIEAP flap reconstruction surgery.

Deep inferior epigastric artery perforator (DIEAP) flap reconstruction surgeries can potentially benefit from augmented reality (AR) in the context of surgery planning and outcomes improvement. Although three-dimensional (3D) models help visualize and map the perforators, the anchorage of the models to the patient's body during surgery does not consider eventual skin deformation from the moment of computed tomography angiography (CTA) data acquisition until the position of the patient while in surgery. In this work, we compared the 3D deformation registration from supine arms down (CTA position) to supine with arms at 90° degrees (surgical position), estimating the patient's skin deformation. We processed the data sets of 20 volunteers with a 3D rigid registration tool and performed a descriptive statistical analysis and statistical inference. With 2.45 mm of root mean square and 2.89 mm of standard deviation, results include 30% cases of deformation above 3 mm and 15% above 4 mm. Pose transformation deformation indicates that 3D surface data from the CTA scan position differs from data acquired in loco at the surgical table. Such results indicate that research should be conducted to construct accurate 3D models using CTA data to display on the patient, while considering projection errors when using AR technology.

Preclinical dental students self-assessment of an improved operative dentistry virtual reality simulator with haptic feedback.

To test and evaluate the second installment of DENTIFY, a virtual reality haptic simulator for Operative Dentistry (OD), on preclinical dental students, by focusing on user performance and self-assessment. Twenty voluntary unpaid preclinical dental students, with different background experience, were enrolled for this study. After the completion of an informed consent, a demographic questionnaire, and being introduced to the prototype (on the first testing session), three testing sessions followed (S1, S2, S3). Each session involved the following steps: (I) free experimentation; (II) task execution; S3 also included (III) completion of questionnaires associated with the experiment (total of 8 Self-Assessment Questions (SAQ)); and (IV) guided interview. As expected, drill time decreased steadily for all tasks when increasing prototype use, verified by RM ANOVA. Regarding performance metrics (Comparisons by Student's t-test and ANOVA) recorded at S3, in overall, a higher performance was verified for participants with the following characteristics: female, non-gamer, no previous VR experience and with over 2 semesters of previous experience of working on phantom models. The correlation between the participants' performance (drill time), for the four tasks, and user self-assessment evaluation, verified by Spearman's rho analysis, allowed to conclude that a higher performance was observed in students who responded that DENTIFY improved their self perception of manual force applied. Regarding the questionnaires, Spearman's rho analysis showed a positive correlation between the improvement DENTIFY inputs on conventional teaching sensed by students, also enhancing their interest in learning OD, their desire to have more simulator hours and the improvement sensed on manual dexterity. All participating students adhered well to the DENTIFY experimentation. DENTIFY allows for student self-assessment and contributes to improving student performance. Simulators with VR and haptic pens for teaching in OD should be designed as a consistent and gradual teaching strategy, allowing multiplicity of simulated scenarios, bimanual manipulation, and the possibility of real-time feedback to allow for the student's immediate self-assessment. Additionally, they should create performance reports per student to ensure self-perception/criticism of their evolution over longer periods of learning time.

A finite element model to simulate femoral fractures in calves: testing different polymers for intramedullary interlocking nails.

OBJECTIVE: To verify if the finite element method can correctly estimate the performance of polyacetal and polyamide 6 intramedullary nails in stabilizing a femoral fracture in calves and to estimate the performance of a polypropylene nail in same conditions. STUDY DESIGN: Computational and experimental study. SAMPLE POPULATION: Finite element models (FEMs). METHODS: Based on a 3-dimensional finite element method (FEM) of the femoral diaphysis, 3 models were constructed to simulate an oblique simple fracture stabilized by an intramedullary nail composed of 1 of 3 distinct polymers. Models were tested under 6 loading conditions that simulated a static calf or a calf in different walking phases. Maximum bone and implant stresses were compared to yield and rupture stresses of specific materials. RESULTS: Under static conditions, all polymers were resistant to critical deformation and rupture because maximum von Mises stresses were lower than the respective yield and rupture stresses. However, during walking, maximum stresses exceeded the yield and rupture limits of the polymers, in agreement with a previous in vivo study, which used polyacetal and polyamide nails. CONCLUSIONS: FEM correctly estimated that polyacetal and polyamide 6 nails would fail to immobilize an oblique femoral diaphyseal fracture in calves that were allowed to walk freely during the early postoperative period. FEM can be useful in the development of new bovine orthopedic devices.

Costovertebral Osteoarthrosis: Rare Differential Diagnosis of Back pain in young patients. Case Report.

The differential diagnosis of dorsal thoracic pain can be a challange due to the proximity of the dorsal column to vital organs as well as to its unique anatomy, innervation, and rib joint. The patterns of referred visceral pain require, in most cases, extensive complementary diagnostic tests in order to exclude severe conditions. Referred pain patterns often result in numerous and expensive visceral workups in order to exclude serious conditions, and costovertebral joint osteoarthritis is usually only considered when the origin of the pain remains unexplained. The authors present the case of a 40-year-old man with disabling dorsal pain due to isolated costovertebral osteoarthrosis. The symptomatology was controlled after injection of methylprednisolone guided by computed tomography. This clinical case aims to describe the clinical presentation of a rare entity that should be considered in the differential diagnosis of back pain.

Motion envelopes: unfolding longitudinal rotation data from walking stick-figures.

This work presents Motion Envelopes (ME), a simple method to estimate the missing longitudinal rotations of minimal stick figures, which is based on the spatial-temporal surface traced by line segments that connect contiguous pairs of joints. We validate ME by analyzing the gait patterns of 6 healthy subjects, comprising a total of 18 gait cycles. A strong correlation between experimental and estimated data was obtained for lower limbs and upper arms, indicating that ME can predict their longitudinal orientation in normal gait, hence, ME can be used to complement the kinematic information of stick figures whenever it is incomplete.