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1.
Science ; 378(6624): 1092-1097, 2022 12 09.
Article En | MEDLINE | ID: mdl-36480631

Programming is a powerful and ubiquitous problem-solving tool. Systems that can assist programmers or even generate programs themselves could make programming more productive and accessible. Recent transformer-based neural network models show impressive code generation abilities yet still perform poorly on more complex tasks requiring problem-solving skills, such as competitive programming problems. Here, we introduce AlphaCode, a system for code generation that achieved an average ranking in the top 54.3% in simulated evaluations on recent programming competitions on the Codeforces platform. AlphaCode solves problems by generating millions of diverse programs using specially trained transformer-based networks and then filtering and clustering those programs to a maximum of just 10 submissions. This result marks the first time an artificial intelligence system has performed competitively in programming competitions.

4.
Nature ; 602(7897): 414-419, 2022 02.
Article En | MEDLINE | ID: mdl-35173339

Nuclear fusion using magnetic confinement, in particular in the tokamak configuration, is a promising path towards sustainable energy. A core challenge is to shape and maintain a high-temperature plasma within the tokamak vessel. This requires high-dimensional, high-frequency, closed-loop control using magnetic actuator coils, further complicated by the diverse requirements across a wide range of plasma configurations. In this work, we introduce a previously undescribed architecture for tokamak magnetic controller design that autonomously learns to command the full set of control coils. This architecture meets control objectives specified at a high level, at the same time satisfying physical and operational constraints. This approach has unprecedented flexibility and generality in problem specification and yields a notable reduction in design effort to produce new plasma configurations. We successfully produce and control a diverse set of plasma configurations on the Tokamak à Configuration Variable1,2, including elongated, conventional shapes, as well as advanced configurations, such as negative triangularity and 'snowflake' configurations. Our approach achieves accurate tracking of the location, current and shape for these configurations. We also demonstrate sustained 'droplets' on TCV, in which two separate plasmas are maintained simultaneously within the vessel. This represents a notable advance for tokamak feedback control, showing the potential of reinforcement learning to accelerate research in the fusion domain, and is one of the most challenging real-world systems to which reinforcement learning has been applied.

5.
Skinmed ; 19(2): 137-141, 2021.
Article En | MEDLINE | ID: mdl-33938438

A 63-year-old woman from Central Florida presented to an outside clinic with a 2-year history of a progressive, asymptomatic cutaneous eruption and arthralgias. Her past medical history was significant for reported seronegative rheumatoid arthritis, for which adalimumab, methotrexate, and low-dose prednisone therapy were initiated 5 years prior. The skin eruption occurred shortly after a 4-week hospitalization during which these medications were withheld. At her initial outside evaluation, a biopsy was performed and interpreted as subacute cutaneous lupus erythematosus (SCLE). She was treated with hydroxychloroquine without improvement. A repeat biopsy was reported as consistent with interstitial granulomatous dermatitis (IGD). There was no improvement with potent topical corticosteroids.


Glucocorticoids/therapeutic use , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Cutaneous/drug therapy , Anti-Inflammatory Agents/therapeutic use , Dermatitis/complications , Dermatitis/diagnosis , Female , Florida , Humans , Middle Aged , Prednisolone/therapeutic use
6.
Int J Dermatol ; 58(9): 997-1007, 2019 Sep.
Article En | MEDLINE | ID: mdl-30900757

Pemphigus herpetiformis (PH), a rare type of pemphigus, is characterized by immunologic findings consistent with pemphigus but with a unique clinical and pathologic presentation. PH was first described as resembling dermatitis herpetiformis clinically, but because of its variable presentation, it can also resemble linear immunoglobulin A bullous dermatosis and bullous pemphigoid. We reviewed reported cases to analyze the most frequent clinical, pathologic, and immunologic characteristics and to propose corresponding diagnostic criteria. Through a comprehensive review of Medline and PubMed databases, 96 publications and 158 cases were identified. After reviewing the reported characteristics of PH, we suggest the following diagnostic criteria: Clinical: 1) pruritic herpetiform intact blisters with/without erosions; and/or 2) pruritic annular or urticarial erythematous plaques with/without erosions; Pathologic: 1) intraepidermal eosinophils or neutrophils, or both; and/or 2) intraepidermal split with/without acantholysis; Immunologic: 1) direct immunofluorescence showing immunoglobulin G with/without C3 intercellular deposits; and/or 2) indirect immunofluorescence showing immunoglobulin G to epithelial cell surface; and/or 3) detection of serum autoantibodies against desmogleins (1,3) or desmocollins (1,2,3), or both. Diagnosis requires one clinical, one pathologic, and one immunologic feature. We also report three new cases diagnosed at our institution to demonstrate the applicability of the suggested criteria.


Dermatitis Herpetiformis/diagnosis , Pemphigus/diagnosis , Skin/pathology , Dermatitis Herpetiformis/immunology , Dermatitis Herpetiformis/pathology , Diagnosis, Differential , Humans , Linear IgA Bullous Dermatosis/diagnosis , Pemphigoid, Bullous/diagnosis , Pemphigus/immunology , Pemphigus/pathology , Skin/immunology
8.
J Fam Pract ; 67(1): 34-36, 2018 01.
Article En | MEDLINE | ID: mdl-29309471

A 41-year-old, right-hand dominant man sought care at our facility one day after trying to pull his boat out of the water. He'd tried to lift the boat with his hands while his forearms were fully supinated and his elbows were flexed to about 90 degrees. He then felt a sharp burning sensation in his left anterior shoulder and was unable to lift the boat. The patient denied feeling a popping sensation at the time of the injury. He had mild pain at night, but was able to sleep. He said that he had mild diminished strength with elbow flexion, but denied having any numbness, tingling, or discoloration of his skin.


Elbow Joint/physiopathology , Muscle Weakness/physiopathology , Shoulder Pain/physiopathology , Tendon Injuries/diagnosis , Adult , Humans , Male , Physical Examination , Rupture/diagnosis , Rupture/surgery , Tendon Injuries/physiopathology , Tendon Injuries/surgery , Tenodesis
9.
Curr Sports Med Rep ; 15(6): 410-416, 2016.
Article En | MEDLINE | ID: mdl-27841812

Water polo is a unique team sport combining swimming sprints and eggbeater kicking, frequent overhead movements and throwing, and regular physical contact with minimal protective equipment. Accordingly, a wide variety of training methods attempt to enhance all of these skill sets. This usually includes some combination of aerobic/anaerobic fitness (via swimming), sport-specific skills, strengthening, and nutrition. In addition, injuries in water polo are somewhat diverse. Physical contact is responsible for the majority of acute injuries, most frequently being injuries to the head and face. The high prevalence of shoulder pain in water polo is likely related to increased shoulder mobility and subsequent instability and stress on shoulder structures, yet the underlying causation is not certain. The unique aspect of shoulder injuries occurring in water polo players is that they may be due to a combination of swimming-related overuse conditions, overhead throwing, and acute trauma-related conditions. Although there is generally minimal evidence-based information available, this article attempts to highlight the current knowledge that we have in regard to water polo injuries and training methods.


Arm Injuries/diagnosis , Arm Injuries/prevention & control , Athletic Injuries/diagnosis , Athletic Injuries/prevention & control , Head Injuries, Closed/diagnosis , Physical Conditioning, Human/methods , Head Injuries, Closed/prevention & control , Humans , Nutrition Therapy/methods , Risk Factors
10.
Dermatol Clin ; 33(3): 579-93, 2015 Jul.
Article En | MEDLINE | ID: mdl-26143433

Leishmaniasis is a parasitic infection endemic to more than 90 countries worldwide. As travel to endemic areas increases, dermatologists need to keep this entity in the differential for any chronic skin lesion in persons who may have had a possible exposure for any duration. It can be difficult to diagnose because manifestations are varied and sometimes subclinical. This article discusses the current state of epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment options. A special focus is placed on cutaneous manifestations and their treatment.


Leishmaniasis, Diffuse Cutaneous/diagnosis , Leishmaniasis, Mucocutaneous/diagnosis , Leishmaniasis, Visceral/diagnosis , Amphotericin B/therapeutic use , Antimony Sodium Gluconate/therapeutic use , Antiprotozoal Agents/therapeutic use , Deoxycholic Acid/therapeutic use , Drug Combinations , Humans , Incidence , Leishmania braziliensis/genetics , Leishmania donovani/genetics , Leishmania mexicana/genetics , Leishmania tropica/genetics , Leishmaniasis, Diffuse Cutaneous/drug therapy , Leishmaniasis, Diffuse Cutaneous/epidemiology , Leishmaniasis, Mucocutaneous/drug therapy , Leishmaniasis, Mucocutaneous/epidemiology , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/epidemiology , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/therapeutic use , Polymerase Chain Reaction , Travel
11.
J Am Acad Dermatol ; 70(2): 269-75.e4, 2014 Feb.
Article En | MEDLINE | ID: mdl-24268786

BACKGROUND: Patch testing is essential for identification of culprits causing allergic contact dermatitis. OBJECTIVE: We sought to identify trends and allergen changes in our standard series during 2006 to 2010, compared with our previous report (2001-2005). METHODS: We conducted a retrospective review of patch-test results. RESULTS: A total of 3115 patients were tested with a mean of 73.0 allergens. Since our prior report, 8 allergens were added to the standard series; 14 were deleted. Significantly higher rates of allergic positive reaction were documented for carba mix, 3%, and Disperse Orange 3, 1%. Rates were lower for 10 allergens: neomycin sulfate, 20%; gold sodium thiosulfate, 0.5%; hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, 1%; disperse blue 124, 1%; disperse blue 106, 1%; diazolidinyl urea, 1%; hexylresorcinol, 0.25%; diazolidinyl urea, 1% aqueous; 2-bromo-2-nitropropane-1,3-diol, 0.25%; and lidocaine, 5%. Many final patch-test readings for many allergens were categorized as mild reactions (erythema only). Overall allergenicity and irritancy rates declined significantly since our prior report. Results were generally comparable with those in a North American Contact Dermatitis Group report from 2005 to 2006. LIMITATIONS: This was a retrospective study; there is a lack of long-term follow-up. CONCLUSIONS: Since our previous report, our standard series composition has changed, and overall rates of allergenicity and irritancy have decreased. Notably, many final patch-test readings showed mild reactions.


Allergens , Dermatitis, Allergic Contact/etiology , Patch Tests/standards , Academic Medical Centers , Adult , Aged , Azo Compounds/immunology , Cohort Studies , Dermatitis, Allergic Contact/diagnosis , Female , Gold Sodium Thiosulfate/immunology , Humans , Male , Middle Aged , Minnesota , Nitroparaffins/immunology , Patch Tests/trends , Piperidines/immunology , Propane/analogs & derivatives , Propane/immunology , Reference Standards , Retrospective Studies , Sensitivity and Specificity , Young Adult
13.
J Am Acad Dermatol ; 67(3): e91-104, 2012 Sep.
Article En | MEDLINE | ID: mdl-21885155

BACKGROUND: Peristomal dermatitis is a common problem in patients with ostomies that is a source of considerable morbidity. Irritant contact dermatitis is most common, but allergic contact dermatitis can also occur. Because of the lack of published reports on patch testing for this indication, we undertook a retrospective study of patch testing results in patients with suspected peristomal allergic contact dermatitis. OBJECTIVE: We sought to describe our patch testing experience with patients referred with peristomal dermatitis. METHODS: This was a retrospective review of medical records of patients with ostomies and peristomal dermatitis who underwent patch testing in the Mayo Clinic Departments of Dermatology in Jacksonville, FL; Rochester, MN; and Scottsdale, AZ, during a 10-year period (2000-2010). RESULTS: Ten patients with peristomal dermatitis were referred for patch testing (6 in Minnesota, 2 in Florida, and 2 in Arizona). Patients were patch tested to the materials used in their stoma devices, to the standard series, and in some cases to supplemental series. All 10 had at least one allergic patch test reaction, most commonly to stoma paste (3 of 10 patients). LIMITATIONS: Retrospective nature of study via chart review is a limitation. CONCLUSION: Patch testing is a useful tool for identification of allergens in patients with peristomal dermatitis.


Dermatitis, Contact/immunology , Patch Tests , Surgical Stomas , Aged , Allergens , Female , Humans , Male , Middle Aged , Ostomy , Retrospective Studies , Surgical Stomas/adverse effects
14.
Int J Dermatol ; 50(11): 1353-1361, 2011 Nov.
Article En | MEDLINE | ID: mdl-22004487

BACKGROUND: Do patch test results vary from one part of the USA to another? Few reports directly compare the results of patch testing across centers within the USA. OBJECTIVES: Our objective was to compare results of patch testing from three geographically disparate Mayo Clinic sites in the USA to ascertain whether there are any differences in allergic patch test rates. METHODS: We retrospectively reviewed patch test results for patients tested with a standard allergen series using our enterprise-wide protocol for patch testing. We compared data collected from January 1, 2001, through to December 31, 2007, from our practice sites in the Midwest, Southwest, and Southeast regions of the USA. RESULTS: In total, 5063 patients underwent patch testing. The mean (standard deviation) number of allergens tested per patient was 70.3 (3.8) (range: 10-87; interquartile range: 68-73). Analyses were conducted separately for 72 allergens with positive reactions from at least 20 patients. Risk-adjusted positive reaction rates (RAPRRs) for 44 allergens differed significantly (P<0.05) among the geographic sites; RAPRRs differed significantly across all three sites for 11 allergens and between two of the three sites for 33 allergens. CONCLUSIONS: Allergic patch test rates differed among our three practice sites for many allergens. It is likely that many factors contributed to these observed differences, including variations in the population undergoing patch testing, variations in allergen exposure, and variations in climate.


Allergens , Dermatitis, Allergic Contact/diagnosis , Patch Tests/statistics & numerical data , Adult , Female , Humans , Logistic Models , Male , Midwestern United States , Retrospective Studies , Southeastern United States , Southwestern United States
15.
Dermatitis ; 22(5): 256-71, 2011.
Article En | MEDLINE | ID: mdl-22652903

BACKGROUND: The standard allergen series used in patch testing contains metals that most commonly cause allergic contact dermatitis, but testing with additional metal allergens is warranted for select patients. OBJECTIVE: To report our experience with patch testing of metals. METHODS: We retrospectively analyzed outcomes of 1,112 patients suspected of having metal allergies. Patients were seen from January 1, 2000, through December 31, 2009. Patch testing was performed with 42 metal preparations (6 in the standard series, 36 in the metal series). RESULTS: Patch testing most commonly was performed for patients with oral disease (almost half the patients), hand dermatitis, generalized dermatitis, and dermatitis affecting the lips, legs, arms, trunk, or face. At least one positive reaction was reported for 633 patients (57%). Metals with the highest allergic patch-test reaction rates were nickel, gold, manganese, palladium, cobalt, Ticonium, mercury, beryllium, chromium, and silver. Metals causing no allergic patch-test reactions were titanium, Vitallium, and aluminum powder. Metals with extremely low rates of allergic patch-test reactions included zinc, ferric chloride, and tin. Reaction rates varied depending on metal salt, concentration, and timing of readings. CONCLUSION: Many metals not in the standard series were associated with allergic patch-test reactions. The many questions raised by these findings, concerning patch testing with individual metals, will be the subject of future studies.


Allergens/adverse effects , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Metals/adverse effects , Patch Tests/methods , Female , Humans , Male , Retrospective Studies
16.
J Am Acad Dermatol ; 59(3): 405-17, 2008 Sep.
Article En | MEDLINE | ID: mdl-18556089

BACKGROUND: There is concern that the immunologic tumor malignant melanoma (MM) may have worse outcomes in immunosuppressed hosts than in the general population. OBJECTIVE: We sought to describe outcomes of MM in immunosuppressed solid organ transplant recipients and compare them with the general population. METHODS: We conducted a retrospective review of medical charts and pathology slides of cases of MM and solid organ transplantation between 1978 and 2007, with comparison of outcomes. RESULTS: In all, 48 MMs were identified in 43 transplant recipients. No patient with MM before transplant receipt had melanoma recurrence, subsequent metastasis, or death caused by melanoma. Of patients with MM diagnosed after transplantation, metastases developed in 3 patients, and two patients died of melanoma. LIMITATIONS: Retrospective review and low number of cases are limitations. CONCLUSIONS: Outcomes of MM in immunosuppressed transplant recipients appeared similar to those in prognostically matched nonimmunosuppressed hosts. The small number of cases limited statistical comparisons.


Immunocompromised Host , Melanoma/etiology , Organ Transplantation , Skin Neoplasms/etiology , Skin/pathology , Adult , Aged , Female , Humans , Kaplan-Meier Estimate , Male , Melanoma/diagnosis , Melanoma/mortality , Melanoma/secondary , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Retrospective Studies , Skin Neoplasms/diagnosis , Skin Neoplasms/mortality , Skin Neoplasms/secondary , Time Factors , United States
17.
Cutis ; 81(5): 409-12, 2008 May.
Article En | MEDLINE | ID: mdl-18543591

We present a case of larva currens in a patient scheduled for renal transplant. Larva currens is an eruption caused by Strongyloides stercoralis, characterized most often by a pathognomonic, migratory, rapidly extending, serpiginous, urticarial eruption. Infected patients who are immunocompromised are at risk for disseminated and often fatal infection. In disseminated disease, diffuse petechiae and purpura may be present, and periumbilical ecchymoses may resemble thumbprints. The dermatologist may be in a unique position to diagnose this condition and institute therapy. Although found endemically in the United States, the increasingly international nature of medical practice and transplantation medicine causes an increase in the number of patients who may present for evaluation.


Skin Diseases, Parasitic/diagnosis , Strongyloides stercoralis/isolation & purification , Strongyloidiasis/diagnosis , Animals , Eosinophilia , Female , Humans , Immunocompromised Host , Kidney Transplantation , Middle Aged , Polycystic Kidney Diseases/complications , Polycystic Kidney Diseases/surgery , Skin/pathology , Skin Diseases, Parasitic/complications , Skin Diseases, Parasitic/immunology , Strongyloidiasis/complications , Strongyloidiasis/immunology
18.
Radiographics ; 27(2): 509-23, 2007.
Article En | MEDLINE | ID: mdl-17374866

A wide variety of superficial soft-tissue masses may be seen in clinical practice, but a systematic approach can help achieve a definitive diagnosis or limit a differential diagnosis. Superficial soft-tissue masses can generally be categorized as mesenchymal tumors, skin appendage lesions, metastatic tumors, other tumors and tumorlike lesions, or inflammatory lesions. With regard to their imaging features, these masses may be further divided into lesions that arise in association with the epidermis or dermis (cutaneous lesions), lesions that arise within the substance of the subcutaneous adipose tissue, or lesions that arise in intimate association with the fascia overlying the muscle. The differential diagnosis may be limited further by considering the age of the patient, anatomic location of the lesion, salient imaging features, and clinical manifestations.


Diagnostic Imaging/methods , Soft Tissue Infections/diagnosis , Soft Tissue Neoplasms/diagnosis , Diagnosis, Differential , Humans , Practice Guidelines as Topic
20.
Cutis ; 69(6): 439-42, 2002 Jun.
Article En | MEDLINE | ID: mdl-12078845

Cutaneous sporotrichosis is an uncommon infection, usually reported as sporadic cases resulting from inoculation with sharp environmental vegetative matter. We report such a case of multiple primary inoculations acquired from Solenopsis (fire ant) stings in a 54-year-old white man. The patient was treated effectively with itraconazole 200 mg twice a day for 4 months.


Ant Venoms/adverse effects , Ants/pathogenicity , Insect Bites and Stings/complications , Sporotrichosis/etiology , Animals , Antifungal Agents/therapeutic use , Humans , Insect Bites and Stings/drug therapy , Itraconazole/therapeutic use , Male , Middle Aged , Sporotrichosis/drug therapy
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