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By: H. Falk, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.

Co-Director, Rowan University School of Osteopathic Medicine

First, an initial correction of the large-scale variation in brightness found in most fundus photographs was applied. The main idea was to level the background such that the reflectance was uniform over the entire macula. The pixel gray levels were used as input for fitting into the custom software employing least-squares methods. After the geo- metric model of the macula was created, it was subtracted from the original image to obtain a leveled image. The process was automatically iterated until a sufficient leveling has been achieved. In other words, the range of gray levels in the image is minimized to an acceptable level. The drusen, which is superimposed on the image, appears brighter than the regular intensity of the background. The final threshold was obtained by applying a histogram analysis approach to the final leveled image (33). An optimal threshold defined the separation of background areas from drusen areas. One advantage of automation is portability of the software to use at other institutions. Despite the advances in automated quantification of drusen, some obstacles still remain. A computer ultimately must be taught how to differentiate drusen from other lesions. Implementation with neural networks or morphological criteria may prove effective in eliciting unique features in the lesions. For now, some cases may still require supervision in digital automated segmentation. Originally used as a research tool, it is increasingly favored with other clinical imaging standards now. Moreover, pupil dilation is unnecessary, and light levels are dim during acquisition (34). This light source reveals structures that intrinsically fluoresce, primarily due to lipofuscin and its main fluorophore, A2E (35,36). Using an algorithm that finds the lower and upper thresholds, the macula is divided into three sections: vessels and darker perivasculature, normal background, and bright drusen. The normal background was used to calculate the mathematical model, displayed as a contour graph (c). The model was subtracted from the original image to yield a background leveled image of uniform intensity in (d). The algorithm then uses the leveled image (d) to calculate a threshold that determines the drusen areas (segmented in green) and overlaid on top of the contrast enhanced layer (f). In the United States, less than one-half of the diabetic population received an annual eye examination (42). One of the goals of telemedicine is to bridge the gap between places where patients can be evaluated and where service is rendered. With the advent of telemedicine and digital photography, the patient and doctor do not even have to be in the same room. Telemedicine Framework the goal of telemedicine is to establish a screening system with the ability to reach out to millions of unexamined patients for primary prevention. The following guidelines can be used to set up a generalized framework for telemedicine. We will use an ophthalmology setting as an example: First, a patient will come into a primary care office to have their retina imaged. The fundus photograph is then sent electronically to a reading center, which can be established at a far away university or hospital. A grader at each institution independently ran the software and performed drusen quantification successfully, thus demonstrating portability and potential for automated software examinations. The results of the grading with software are comparable to grading manually by stereo-viewing.

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Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. Drug Maker Forest Pleads Guilty; to pay more than $313 million to resolve criminal charges and False Claims Act allegations. National trends in the office-based treatment of children, adolescents, and adults with antipsychotics. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Design and reporting modifications in industry-sponsored comparative psychopharmacology trials. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. They disturb the lucrative status quo where people around them benefit handsomely from industry money: colleagues and bosses, the hospital, the university, the specialist society, the medical association and some politicians. However, whistle-blowers are not motivated by possible financial bounty, but by their conscience. All the companies I have studied engage deliberately in criminal activities, and in the United States, there is a log of nearly a thousand healthcare qui tam cases (in which whistle-blowers with direct knowledge of the alleged fraud initiate the litigation on behalf of the government), and the Justice Department has suggested that the problem may get worse. Those who threaten the income from the crimes are exposed to violence, the difference being that in the drug industry, the violence is not of a physical but psychological nature, which can be equally devastating. This violence includes intimidation, instigation of fear, threats of firing or legal proceedings, actual firing and litigation, unfounded accusations of scientific misconduct, and other attempts at defamation and destruction of research careers. Astra had manufactured thalidomide, but the lawyer had enormous difficulty finding experts who were willing to testify against Astra. Maybe they should have thought about the malformed children, or about the millions of people the Nazis had murdered shortly before this that were also considered to be subhuman and of no value. No guilty verdict was ever rendered, no personal responsibility was assigned, and no one went to prison. It took 16 years before the incriminating evidence that had been described in an article the Sunday Times was forbidden to print finally came to public knowledge. This was only because the affair ended in the European Court where Prime Minister Margaret Thatcher was asked to explain the mysteries of English law, the rationale of which no one on the continent could understand. The threats can be particularly malignant when scientists have found lethal harms with marketed drugs that the companies have successfully concealed. He was interested in knowing how she had gotten access to documents that the company considered strictly confidential. He called again and threatened her by saying that journalists who are critical towards the drug industry may lose everything, their family, friends and job. This occurred despite the fact that the contract gave the researchers permission to publish. Out of courtesy, they showed a copy of the peer-reviewed article to the manufacturers, who threatened legal action. The article was never published, despite getting to proof stage, and it took another 12 years before the drug agency withdrew the marketing authorisation for evening primrose oil.

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Hallucinogenic stimulant: euphoria, disinhibition, hyperactivity, distorted sensory and time perception, teeth clenching. Lifethreatening effects include hypertension, tachycardia, hyperthermia, hyponatremia, serotonin syndrome. Long-acting oral opiate used for heroin detoxification or long-term maintenance therapy. Sublingually, buprenorphine (partial agonist) is absorbed and used for maintenance therapy. Alcoholism Physiologic tolerance and dependence on alcohol with symptoms of withdrawal when intake is interrupted. Complications: alcoholic cirrhosis, hepatitis, pancreatitis, peripheral neuropathy, testicular atrophy. Treatment: disulfiram (to condition the patient to abstain from alcohol use), acamprosate, naltrexone, supportive care. Support groups such as Alcoholics Anonymous are helpful in sustaining abstinence and supporting patient and family. May progress to irreversible memory loss, confabulation, personality change (Korsakoff syndrome). Symptoms may be precipitated by giving dextrose before administering vitamin B1 to a patient with thiamine deficiency. Characterized by autonomic hyperactivity (eg, tachycardia, tremors, anxiety, seizures), electrolyte disturbances, respiratory alkalosis. Low potency: Chlorpromazine, Thioridazine (Cheating Thieves are low)-anticholinergic, antihistamine, 1-blockade effects. Endocrine: dopamine receptor antagonism hyperprolactinemia galactorrhea, oligomenorrhea, gynecomastia. Treatment: benztropine (acute dystonia, tardive dyskinesia), benzodiazepines, -blockers (akathisia). Use clozapine for treatment-resistant schizophrenia or schizoaffective disorder and for suicidality in schizophrenia. Tremor, hypothyroidism, polyuria (causes nephrogenic diabetes insipidus), teratogenesis. Sedation, 1-blocking effects including postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). Confusion and hallucinations in elderly due to anticholinergic side effects (nortriptyline better tolerated in the elderly). Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in anorexic/bulimic patients. Toxicity: sedation (which may be desirable in depressed patients with insomnia), appetite, weight gain (which may be desirable in elderly or anorexic patients), dry mouth. Toxicity: nausea, sexual dysfunction, sleep disturbances (abnormal dreams), anticholinergic effects. Mesonephros-functions as interim kidney for 1st trimester; later contributes to male genital system. Degenerated pronephros Mesonephros Metanephric mesenchyme Ureteric bud Urogenital sinus Mesonephric duct Metanephros Potter sequence (syndrome) A Oligohydramnios compression of developing fetus limb deformities, facial anomalies (eg, low-set ears and retrognathia A, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs pulmonary hypoplasia (cause of death). As they ascend from pelvis Aorta during fetal development, horseshoe kidneys Renal artery get trapped under inferior mesenteric artery and remain low in the abdomen. Associated with hydronephrosis (eg, ureteropelvic Inferior junction obstruction), renal stones, infection, mesenteric artery chromosomal aneuploidy syndromes (eg, Turner syndrome; trisomies 13, 18, 21), and rarely renal cancer. A Congenital solitary functioning kidney Unilateral renal agenesis Multicystic dysplastic kidney Condition of being born with only one functioning kidney. Majority asymptomatic with compensatory hypertrophy of contralateral kidney, but anomalies in contralateral kidney are common.

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Cold treatments of rooms or buildings to control bedbugs have not been well studied or used often, but freezing of furniture or other items within containers or chambers may be a practical alternative for limited infestations or to augment other control measures. Controlled atmospheres In a small series of very preliminary laboratory tests conducted by the German Federal Environmental Agency, all life stages of common bedbugs were reportedly killed within 24 hours or less by constant exposure to very high concentrations of carbon dioxide gas at ambient atmospheric pressure, but they were not affected very much by high concentrations of nitrogen gas under those same conditions (Herrmann et al. Pesticide applications Currently, the exclusive use of non-insecticide control products and techniques is not effective or efficient enough to be practical. Even their use as a primary means for controlling or eliminating an established bedbug population is ineffective. Still one of the most effective, practical and quickest ways to reduce the size of an established bedbug infestation is the use of a precisely placed (but thorough) application of a properly labelled, registered and adequately formulated residual insecticide. Effective control usually consists of applying interior sprays or dusts to surfaces that the bedbugs crawl over to reach the host, as well as applying them to cracks and crevices where they rest and hide. Microencapsulated formulations and dust formulations have a longer residual effect than other formulations. Synergized pyrethrins not only show high lethal activity against the bugs, but they also show the ability to flush them out, allowing quicker analysis of the infested area. Modified diatomaceous earths with hydrophobic surfaces can also be used to treat cracks and crevices. Retreatment, however, is essential and should be carried out at not less than two-week intervals until the population has been eradicated. True fumigation of small volumes or limited amounts of furniture, clothing, or other personal items can kill all stages of bedbugs present, possibly including bedbug eggs. Such a treatment, however, would not prevent reinfestation immediately after the fumigant had been sufficiently removed for the items treated to be used again. Surface treatments Limited, precisely placed treatments of selected surfaces, using properly formulated residual insecticides, can provide at least a temporary lethal (or perhaps repellent) barrier and thus can help reduce biting of nearby hosts. Impregnated fabric and bednets Fabrics and bednets that are factory- or self-impregnated with licensed and commercially available formulations of residual insecticides can help deny bedbugs access to hosts and may even kill some of the bugs that crawl across them. This can be economical, since some spray, dipping or coating formulations of products containing permethrin will remain on clothing at their full applied strength through six or more launderings, or even for the life of the fabric (Lindsay et al. This treatment is done during the manufacture of the fabric and not by a pest control company when the fabric is in place. There is a recent report of pyrethroid resistance to the use of treated bednets in a population of tropical bedbugs (Myamba et al. Most of them can stimulate bedbugs hidden in harbourages to become active and move out into the open, allowing them to be noticed more easily. Some of those bugs may be killed by prolonged or repeated exposures, but control would be successful for only a small percentage of the bugs flushed from harbourages. Crack-and-crevice treatments Because bedbugs habitually hide clustered together in cracks and narrow harbourages, precisely applied crack-and-crevice treatments may often be among the most effective 146 control techniques to use against them. Several different active ingredients and formulations have been licensed and are currently used against bedbugs, and a variety of insecticide formulations and devices must be used to treat infested harbourages. As per label directions, applications of dust formulations should be used in electrical outlet boxes and in other places where it is desirable to use a minimum-risk, long-lasting insecticide. Most residual insecticides that are labelled (or licensed) or recommended for the control of bedbugs are only intended for use as a crack-and-crevice treatment, according to directions on their product labels. The vast majority of such currently available products are either natural or synthetic pyrethroids; some of these products include synergistic chemicals as well. For any class of insecticide product active ingredient included in products currently labelled for use to control bedbugs, type I pyrethroids are among the least toxic. The application concentration of pyrethroid active ingredients registered as bedbug control products is seldom more than 1% v/v. Also, most non-residual pyrethroids are rapidly detoxified by normal exposure to sunlight, oxygen in air, common household cleaning agents and microbes routinely found on nearly all exposed surfaces.

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