Semantic and Generalized Entropy Loss Functions for Semi-Supervised Deep Learning.

The increasing size of modern datasets combined with the difficulty of obtaining real label information (e.g., class) has made semi-supervised learning a problem of considerable practical importance in modern data analysis. Semi-supervised learning is supervised learning with additional information on the distribution of the examples or, simultaneously, an extension of unsupervised learning guided by some constraints. In this article we present a methodology that bridges between artificial neural network output vectors and logical constraints. In order to do this, we present a semantic loss function and a generalized entropy loss function (Rényi entropy) that capture how close the neural network is to satisfying the constraints on its output. Our methods are intended to be generally applicable and compatible with any feedforward neural network. Therefore, the semantic loss and generalized entropy loss are simply a regularization term that can be directly plugged into an existing loss function. We evaluate our methodology over an artificially simulated dataset and two commonly used benchmark datasets which are MNIST and Fashion-MNIST to assess the relation between the analyzed loss functions and the influence of the various input and tuning parameters on the classification accuracy. The experimental evaluation shows that both losses effectively guide the learner to achieve (near-) state-of-the-art results on semi-supervised multiclass classification.

PhenomeCentral: a portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases.

The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org). Each record includes a phenotypic description and relevant genetic information (exome or candidate genes). PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered.

A novel short-scar breast reduction technique in large breasts.

BACKGROUND: Short-scar breast reduction techniques have become very popular in the last two decades. These techniques cannot be used very often in patients with exceptionally large breasts because of the excessive amounts of redundant skin. In this article we describe our new approach for dealing with the extra skin remaining in patients with very large breasts so that they may also benefit from the short-scar breast reduction procedure. METHODS: In our technique the vertical suture line is divided into two separate suture lines. The first suture line follows the natural curve of the lower pole of the breast from the nipple to the chest wall. This line is elongated by elevating and anchoring the new inframammary fold higher on the chest wall with a suspensory suture and the skin is then closed in a straight line. The second suture line attaches the extra lower skin by closing the dermis to the chest wall and then closing the skin with a purse-string suture. This technique helps to deal with the extra skin resulting from the short-scar breast reduction technique. RESULTS: The technique was used in ten patients with large breasts. Patient satisfaction was excellent and there was no increase in complications. The technique also helped to obliterate the dead space beneath the breast and reduced seroma formation. CONCLUSION: We found that this new technique can be used safely and effectively in selected patients with large breasts without any increase in complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The hatchet and bilobed flaps revisited: shedding new light on traditional concepts.

BACKGROUND: The bilobed and hatchet flaps are well-accepted reconstructive options for the correction of defects of the lower third of the nose. Optimal utilization of these flaps depends on understanding the characteristics of each flap as well as anatomic considerations related to the distal nasal area. Disregarding the limitations of either method may lead to flap failure and unacceptable aesthetic results. OBJECTIVE: We present three original ideas: 1) a bilobed flap may be considered as a hatchet flap with a Z-plasty; 2) the trap door deformity (TDD) associated with a bilobed flap can be used as an advantage; and 3) an easy method for preoperative planning of a bilobed flap. METHODS: We collected data from patients who underwent excision of basal cell carcinoma (BCC) of the distal third of the nose and reconstruction with a hatchet or a bilobed flap within the last 20 years. RESULTS: Favorable cosmetic results were achieved when a hatchet flap was used to reconstruct defects of the inferior third of the nasal side wall, above or bordered with the alar crease, and when a bilobed flap was used to reconstruct nasal tip para-medial defects above the lower lateral cartilage convexity. CONCLUSIONS: We suggest choosing between the hatchet and bilobed flaps for nasal reconstruction according to the defect location as outlined by our findings.

Late-onset bloodstream infections in preterm infants: a 2-year survey.

BACKGROUND: We determined the prevalence and risk factors for late-onset bloodstream infections (LO-BSI), the distribution of pathogens and the outcomes of affected preterm infants. METHODS: The records of all preterm infants (<37 weeks gestation) born between 2004 and 2005 and hospitalized in the neonatal intensive care unit for >3 days were retrieved for this retrospective matched case-control study. RESULTS: A total of 108 out of 1459 preterm infants (7.4%) had 142 episodes of LO-BSI. The highest LO-BSI rate (44%) was among 198 very-low-birthweight infants (<1500 g). The most common causative organisms were Coagulase-negative staphylococci and Klebsiella (60% and 13%, respectively). The mean hospital stay was 64 days for LO-BSI preterm infants versus 48 days for non-LO-BSI preterm infants. Congenital malformations and peripheral catheters were independent risk factors for LO-BSI. Crude mortality rates were 6.9% (LO-BSI) and 3.0% (non-LO-BSI), with an LO-BSI-attributable mortality of 3.9%. CONCLUSION: LO-BSI frequently affect very-low-birthweight infants. Strategies to prevent LO-BSI should target peripheral catheters.

Authentication of Rembrandt's self-portraits through the use of facial aging analysis.

The Dutch painter Rembrandt van Rijn (1606-1669) left behind the largest collection of self-portraits in the history of art. Although about 40 of his oil paintings could be considered "self-portraits," controversy still exists regarding 14 of them. We undertook to determine the identity of the painter or the subject. Our work was based on the generally accepted premise that these portraits represent a "realistic" rendering of the subject. Self-portraits on which there is consensus regarding the authenticity were chosen as the basis for our measurements. Using a computerized technique we measured the brow ptosis. We also subjectively analyzed Rembrandt's facial aging and the unique asymmetrical elements in his face. We could not add any useful information on 6 of the 14 portraits and suggest that 8 should be considered authentic. Facial aging analysis and the unique surface anatomy allowed us to confirm Rembrandt as the painter in four of six self-portraits. We confirmed Rembrandt as the subject and painter in three more paintings. Of the two paintings in which the subject's identity was controversial, we determined Rembrandt as the subject in one. We were able to date Rembrandt's age in two other works and considered another portrait to be a copy. Our methodology may serve as an additional tool for the authentication of self-portraits.

The "Brown sisters": photogrammetric analysis of brow and cheek descent.

BACKGROUND: Due to the absence of accurate tools and appropriate photographic material there is a paucity of objective studies on facial aging in the modern literature. OBJECTIVES: To measure changes in two elements of the face: brow ptosis and cheek mass migration, using an objective tool that we developed which we then used to evaluate facial aging in two subjects studying serial professional photographs over a 25 year period. METHODS: We studied the photographic atlas of the "Brown Sisters," a record of the yearly group photograph of four sisters taken by the photographer Nicolas Nixon. For technical reasons only two of the sisters fulfilled the criteria we set for the study. We used the interpupillary distance of each photograph studied to standardize the brow height and cheek mass distance from the interpupillary line. RESULTS: We observed progressive medial brow descent occurring at about the age of 30, with apparent stabilization thereafter. In contrast, there was a continuous process of lateral brow descent through the years. A process of gradual cheek mass descent was noted in the second half of the third decade. CONCLUSIONS: Our results indicate that the dynamic brow changes start in the second half of the third decade, with more significant lateral brow descent than medial brow descent. The cheek mass reflective point moves in an inferior-lateral direction. The tool we developed can be used to follow aging changes and postoperative results, thereby helping the surgeon achieve true rejuvenation surgery.

Dr. Tulp's Anatomy Lesson by Rembrandt: the third day hypothesis.

An autopsy was an important event in 17th century Holland. Autopsies were held in an 'anatomy theater' and performed according to a fixed protocol that often took up to 3 days to complete. Of the five group portraits painted by Rembrandt over the course of his career, two were anatomy lessons given by Dr. Tulp and Dr. Deyman. An examination of Rembrandt's painting Dr. Tulp's Anatomy Lesson (1632) and an X-ray image of the painting, as compared to other paintings of anatomy lessons from the same period, reveal interesting differences, such as positioning, and light and shadow. Not only was the autopsy not performed according to the usual protocol, but in this painting Rembrandt created a unique dramatic scene in his effort to tell a story. We suggest that Dr. Tulp and Rembrandt "modified" the painting of Dr. Tulp's anatomy lesson to emphasize Dr. Tulp's position as the greatest anatomist of his era--"Vesalius of Amsterdam," and as a way of demonstrating God's greatness by highlighting the hand as a symbol of the most glorious of God's creations.

Lack of complications in minor skin lesion excisions in patients taking aspirin or warfarin products.

Many patients undergoing surgical procedures take medications that influence the coagulation system. It is common practice to discontinue the use of aspirin and warfarin products 7 to 10 days before any major surgical procedure. However, there is some controversy as to whether these medications should be discontinued for minor dermatological procedures. Our aim was to study the incidence of complications in patients receiving aspirin or warfarin and undergoing minor dermatological procedures. Two thousand three hundred twenty-six patients, operated on by a single surgeon, were studied for complications. Warfarin was used by 28 patients, 228 took aspirin, and the remainder took neither. There was no difference in the complication rate among the three groups as long as the surgeon diligently obtained hemostasis. It appears that patients taking aspirin or warfarin do not need to discontinue these medications before minor dermatological procedures.

Cutaneous photodamage in schizophrenia patients.

BACKGROUND: Schizophrenia patients frequently engage in unhealthy lifestyle behaviors. The adverse effects of sun exposure on the human skin are well studied but only sparse data in this area have been focused on schizophrenia patients. AIM: To assess the role of sun exposure and its effects on cutaneous photoaging in schizophrenia patients compared with age-matched healthy subjects. METHOD: Skin photoaging was assessed using a modification of Glogau's classification. We developed a rating for aged appearance, applied to facial skin, dorsal hand skin, and a total integrated score. The extent of photodamage was independently evaluated by two of the investigators certified in dermatology and plastic surgery. Each rater independently estimated the subjects' age. Raters were blinded to the subjects' demographic and clinical parameters as well as to each other's ratings. RESULTS: Seventy-four participants were enrolled. There were 37 patients, 24 men and 13 women, mean age: 42.7+/-9.7 years. The comparison group consisted of 20 men and 17 women, mean age: 42.4+/-9.2 years. Age, gender and BMI as well as smoking status did not differ significantly between groups. The variables found to differentiate between groups were: sun exposure, use of sunscreens, overall pigmentary changes, periorbital wrinkles and the intake of concurrent medications. CONCLUSION: Increased cutaneous photoaging in schizophrenia patients, evidenced by reduced sun safety behaviors, and objective clinical signs of skin photodamage were demonstrated in the present study. We suggest that preventive measures like sun safety education should be undertaken by mental health professionals.

Effect of aspirin and heparin on random skin flap survival in rats.

BACKGROUND: Aspirin and heparin are commonly given to patients undergoing microvascular procedures to increase flap survival and patency, yet there is scant information concerning the effect these flaps have on nonmicrovascular flaps. OBJECTIVE: The objective was to obtain baseline values concerning the effect of aspirin and heparin on the viability of standardized flap tissues. METHODS AND MATERIALS: One hundred rats were divided into five groups receiving high-dose aspirin, low-dose aspirin, high-dose aspirin in combination with heparin, and heparin alone and the final group were controls. The viability of the tissue was measured at 1 week by fluorescein fluorescence. RESULTS: There was significant improvement in flap survival in the high-dose aspirin and high-dose aspirin combination groups. CONCLUSIONS: It appears that high-dose aspirin increases survival of ischemic flap tissue irrespective of the presence of microvascular anastomosis and may be of clinical benefit in all flap surgery. The authors have indicated no significant interest with commercial supporters.

Complications of minor skin surgery performed under local anesthesia.

BACKGROUND: Minor surgical procedures performed under local anesthesia are the most common surgical procedures routinely carried out in every plastic surgical practice. OBJECTIVE: The objective was to evaluate the prevalence of immediate local and systemic complications of such procedures. METHODS AND MATERIALS: Records of 2,600 procedures performed under local anesthesia on 2,431 patients between November 2001 and May 2004 were reviewed. Local anesthetic complications and all surgical-related complications were recorded. RESULTS: Procedure-related complications were 51 presyncope (1.9%), 4 true syncope (0.16%), 2 minor burns (0.08%), and 1 facial laceration (0.04%). CONCLUSIONS: True allergic reaction to lidocaine is extremely rare and none was noted in our study. Most patients who claimed that they had suffered from such a reaction were probably experiencing symptoms related to intravenous injection administration, a reaction to the added vasoconstrictor (adrenaline), or a vasovagal reaction, which is a common trait among young adults.

Effect of hyaluronic acid on random-pattern flaps in rats.

BACKGROUND: Hyaluronic acid is a common component of the extracellular matrix, has many medical applications, and is widely used as a soft tissue filler in patients who simultaneously or eventually undergo cosmetic procedures to the areas treated. OBJECTIVE: The objective was to study the effect of hyaluronic acid on wound healing and viability of random-pattern flaps in rats. METHODS AND MATERIALS: Twenty-six male rats were randomly divided into two groups. A cephalically based random dorsal flap was used-14 rats received hyaluronic acid to the bed of the flap immediately after surgery; 12 served as controls. After 1 week, flap survival was evaluated by fluorescein fluorescence. A t-test statistical analysis of survival relationships was performed. RESULTS: Flap viability in hyaluronic acid-treated rats was slightly better than in controls (average flap length survival 46.7 and 40.6 mm, respectively; p<.2). CONCLUSIONS: Although hyaluronic acid had a slight beneficial effect on flap viability, no significant improvement in flap survival was shown. The lack of any deleterious effect of hyaluronic acid on relatively ischemic tissues is further evidence of its harmless effect during surgical intervention. Further studies should be performed to clarify the potential benefit of hyaluronic acid on random flaps. The authors have indicated no significant interest with commercial supporters.

Our experience with a "homemade" vacuum-assisted closure system.

BACKGROUND: Negative-pressure therapy for the closure of wounds, a technique to accelerate secondary wound healing, is clinically available as the V.A.C. system (KCI Inc, San Antonio, TX, U.S.A.). Budgetary considerations in our institution precluded widespread use of the expensive V.A.C. system in routine cases. OBJECTIVES: To develop a less expensive comparably effective dressing, based on the same principles. METHODS: We used our "homemade" system to treat 15 patients with appropriate complex wounds. Their hospital charts were reviewed and assessed retrospectively. Cost analysis was performed comparing our dressing with the V.A.C. system. RESULTS: Our homemade negative-pressure wound treatment system obtained results similar to what one could expect with the V.A.C. system in all parameters. Complications encountered were few and minor. Cost per day using our negative-pressure system for a 10 cm2 wound is about U.S. $1, as compared to U.S. $22, utilizing the V.A.C. system. CONCLUSIONS: Our homemade negative-pressure system proved to be a good cost-effective treatment for wound closure in hospitalized patients, yielding results comparable to those of the more expensive V.A.C. system.

[Diagnostic accuracy of skin lesions excised by a plastic surgeon].

BACKGROUND: Skin tumors are the most common malignancies in the western population, with surgical excision as the definitive treatment. OBJECTIVES: The author's objectives were to estimate the precision of clinical diagnosis of skin tumors by a plastic surgeon in a community clinic. METHODS: The study includes clinical and histological data of patients operated on solely by one plastic surgeon, between November 2001 to July 2003. The sensitivity and positive predictive value were measured and compared to the literature. RESULTS: The study included 1640 patients. Out of 1806 excised skin lesions, 17.4% were malignancies. Basal cell carcinoma was the most common tumor, followed by squamous cell carcinomas and melanomas. Sensitivity for skin malignancy was 94%, and 76.5% for specific skin malignancy. Positive predictable value for any malignancy was 69.4%, and 72% for the basal cell carcinoma, the most common skin malignancy. CONCLUSIONS: Clinical examination is the main diagnostic tool for the plastic surgeon and dermatologist in the evaluation of skin lesions. Surgical excision is considered when clinical diagnosis is not productive or when malignancy is suspected. For most malignancies, diagnostic excision is therapeutic as well. Positive predictable value is a prospective index estimating the clinical diagnostic skills of the clinician. In our opinion, new technologies such as dermatoscopy should be used more often in the evaluation of skin lesions.

The effect of postoperative aspirin on random pattern flaps in rats.

Our laboratory has been studying the effect of aspirin, given alone or in combination with other medications, on random pattern skin flaps. We have consistently found that preoperative aspirin in high doses (200 mg/kg) increases flap survival, apparently as a result of its ability to modify the inflammatory reaction and/or direct vasodilatation, and not as a consequence of antiaggregation of platelets. In an effort to further elucidate how this effect is modulated, we designed this experiment in which we gave aspirin after the operative procedure to simulate an acute clinical surgical problem such as a failing or ischemic flap. Our results failed to show any difference between the rats that received postoperative aspirin and the untreated control group. It would appear that aspirin given postoperatively is not able to counteract the noxious elements that affect flap survival. This work indicates an important relationship between the timing of administration and the beneficial effects of aspirin. By investigating fully the mechanism whereby aspirin is able to improve flap survival, we hope to isolate this mechanism so an alternative pharmacological agent, safer than aspirin, can be found for clinical use.

Rembrandt--aging and sickness: a combined look by plastic surgeons, an art researcher and an internal medicine specialist.

Rembrandt van Rijn (1606-1669) left behind the largest collection of self-portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had.

Asthma and psychiatric disorders in male army recruits and soldiers.

BACKGROUND: Numerous studies have shown an association between asthma and mental disorders. While elevated rates of asthma have been noted among psychiatric patients with anxiety disorders and post-traumatic stress disorder, several studies have found elevated rates of mental disorders among asthma patients. Such studies, however, have generally relied upon questionnaires and assessment by non-specialist physicians to diagnose mental disorders and asthma. OBJECTIVES: To examine a possible association between asthma and psychiatric diagnoses in Israeli military recruits and soldiers. METHODS: In this cross-sectional study we compared the prevalence of mental diagnoses in asthmatic recruits and soldiers with that in non-asthmatic recruits and soldiers. A total of 195,903 recruits and soldiers were examined by Israel Defense Forces recruiting offices and fitness boards. Diagnoses of asthma were based on a pulmonologist's diagnosis, including spirometry at rest and exercise testing as indicated; diagnoses of mental disorders were based on examination by a psychiatrist. RESULTS: The prevalence of asthma was found to be 7.8% (current) and 9.8% (lifetime). The prevalence of mental disorders was 13.4%. Current asthma was associated with an increased likelihood of any mental disorder (OR = 1.20, 95% Cl = 1.15-1.26), and specifically with mood and anxiety disorders (1.31, 1.19-1.46), introvert personality disorders (1.20, 1.12-1.28) and adjustment disorder (1.43, 1.26-1.62). Lifetime asthma was associated with an increased likelihood of the same disorders, but the association was not as powerful. CONCLUSIONS: The results validate the previously documented association between asthma and mental disorders, using a sample of unprecedented size and improved methodology. A multidisciplinary approach to asthma that incorporates mental health professionals in the treatment of poorly controlled asthma and perhaps of asthma in general is recommended.

Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

BACKGROUND: While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. METHODS: This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. RESULTS: Twenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs -0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size=0.17, significance lost following Bonferroni correction). CONCLUSIONS: Vitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation.

Increased use of mental health services related to isotretinoin treatment: a 5-year analysis.

BACKGROUND: The association between exposure to Isotretinoin, the development of depression and suicide attempts is controversial. OBJECTIVE: To retrospectively assess pattern of utilization of mental health services in the Israeli Defense Forces (IDF) during a 5-year period for all subjects exposed to Isotretinoin in comparison to a control group consisting of army conscripts suffering from psoriasis. All subjects were young adults (18 to 21 years old) in compulsory military service. METHOD: Exposure to Isotretinoin mandates reporting and marking as a coded medical profile in the IDFs' computerized medical record of each conscript and soldier. Medical data, tracked by military medical profiles, were summarized from medical records of all subjects treated by Isotretinion during the years 1999-2003 and for the control group for the same period. Use of mental health services was the a-priori defined primary outcome measure. RESULTS: During the study period 1419 subjects were exposed to Isotretinoin and 1102 suffered from psoriasis. Utilization of mental health services was highest for the index group wherein 17.2% (245/1419) of subjects were evaluated or treated compared to 12.5% in the control group (psoriasis). The inter-group differences were statistically significant; Chi-square=15.9 (df=2), p=0.0003. CONCLUSIONS: We suggest that psychiatric evaluation be regularly undertaken prior to initiation of Isotretinion treatment in young adults at risk, as well as providing follow-up visits during and at completion of treatment.