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In Section 3 of our paper, the confusion with indices resulted in the incorrect statement of Theorems 3.3, 3.4, 3.3 ′ and 3.4 ′ (pp. 864–867), as well as influenced Example 4.3 (pp. 872–873). We sincerely apologize and present the corrected version below. [ABSTRACT FROM AUTHOR]

Abstract Introduction Adult Growth hormone Deficiency is a well known phenomenon effecting both males and females. Adult Growth Hormone Deficiency is marked by a number of neuropsychiatric, cognitive performance, cardiac, metabolic, muscular, and bone symptoms and clinical features. There is no known standardized acceptable therapeutic modality to treat this condition. A recent meta-analysis found that after 16 years of Growth Hormone replacement therapy a large proportion of the patients still had Growth Hormone associated symptoms especially related to executive functioning. A major goal is to increase plasma levels of both insulin-like growth factor (insulin-like growth factor-1) and insulin-like growth factor binding protein 3. Case Presentation We report a case of a 45-year-old caucasian woman with early ovarian failure for 2 years and amenorrhea since the age of 43, who presented with Adult Growth Hormone Deficiency and an IGF-1 of 126 ng/mL. Since her insulin-like growth factor-1 was lowest at 81 ng/mL, she was started on insulin-like growth factor-1 Increlex at 0.2 mg at bedtime, which immediately raised her insulin-like growth factor-1 levels to 130 ng/mL within 1 month, and 193 ng/mL, 249 ng/mL, and 357 ng/mL, after 3, 4, and 5 months, respectively, thereafter. Her insulin-like growth factor binding protein 3 continued to decrease. It was at this point when we added back the Growth Hormone and increased her Increlex dosage to 1.3 - 1.5 mg that her insulin-like growth factor binding protein 3 began to increase. Conclusion It appears that in some patients with Adult Growth Hormone Deficiency, insulin-like growth factor-1 elevation is resistant to direct Growth Hormone treatment. Furthermore, the binding protein may not rise with insulin-like growth factor-1. However, a combination of Growth Hormone and insulin-like growth factor-1 treatment may be a solution.

For dynamic equations on time scales with positive variable coefficients and several delays, we prove that nonoscillation is equivalent to the existence of a positive solution for the generalized characteristic inequality and to the positivity of the fundamental function. Based on this result, comparison tests are developed. The nonoscillation criterion is illustrated by examples which are neither delay-differential nor classical difference equations.

Abstract Background Albeit other prospective randomized controlled clinical trials on H-Wave Device Stimulation (HWDS), this is the first randomized double-blind Placebo controlled prospective study that assessed the effects of HWDS on range of motion and strength testing in patients who underwent rotator cuff reconstruction. Methods Twenty-two patients were randomly assigned into one of two groups: 1) H-Wave device stimulation (HWDS); 2) Sham-Placebo Device (PLACEBO). All groups received the same postoperative dressing and the same device treatment instructions. Group I was given HWDS which they were to utilize for one hour twice a day for 90 days postoperatively. Group II was given the same instructions with a Placebo device (PLACEBO). Range of motion was assessed by using one-way ANOVA with a Duncan Multiple Range Test for differences between the groups preoperatively, 45 days postoperatively, and 90 days postoperatively by using an active/passive scale for five basic ranges of motions: Forward Elevation, External Rotation (arm at side), External Rotation (arm at 90 degrees abduction), Internal Rotation (arm at side), and Internal Rotation (arm at 90 degrees abduction). The study also evaluated postoperative changes in strength by using the Medical Research Council (MRC) grade assessed strength testing. Results Patients who received HWDS compared to PLACEBO demonstrated, on average, significantly improved range of motion. Results confirm a significant difference for external rotation at 45 and 90 days postoperatively; active range at 45 days postoperatively (p = 0.007), active at 90 days postoperatively (p = 0.007). Internal rotation also demonstrated significant improvement compared to PLACEBO at 45 and 90 days postoperatively; active range at 45 days postoperatively (p = 0.007), and active range at 90 days postoperatively (p = 0.006). There was no significant difference between the two groups for strength testing. Conclusion HWDS compared to PLACEBO induces a significant increase in range of motion in positive management of rotator cuff reconstruction, supporting other previous research on HWDS and improvement in function. Interpretation of this preliminary investigation while suggestive of significant increases in Range of Motion of Post -Operative Rotator Cuff Reconstruction, warrants further confirmation in a larger double-blinded sham controlled randomized study.

Abstract Background Numerous studies have reported that age-induced increased parathyroid hormone plasma levels are associated with cognitive decline and dementia. Little is known about the correlation that may exist between neurological processing speed, cognition and bone density in cases of hyperparathyroidism. Thus, we decided to determine if parathyroid hormone levels correlate to processing speed and/or bone density. Methods The recruited subjects that met the inclusion criteria (n = 92, age-matched, age 18-90 years, mean = 58.85, SD = 15.47) were evaluated for plasma parathyroid hormone levels and these levels were statistically correlated with event-related P300 potentials. Groups were compared for age, bone density and P300 latency. One-tailed tests were used to ascertain the statistical significance of the correlations. The study groups were categorized and analyzed for differences of parathyroid hormone levels: parathyroid hormone levels 30 (n = 62, mean = 62.4 ± 28.3 SD, p ≤ 02). Results Patients with parathyroid hormone levels 30, which demonstrated greater P300 latency (P300 = 345.7 ± 3.6 SE, p = .02). Participants with parathyroid hormone values 30 (n = 48, M = -1.85 ± .19 SE, p = .04). Conclusion Our findings of a statistically lower bone density and prolonged P300 in patients with high parathyroid hormone levels may suggest that increased parathyroid hormone levels coupled with prolonged P300 latency may become putative biological markers of both dementia and osteoporosis and warrant intensive investigation.

Abstract Background Aging is marked by declines in levels of many sex hormones and growth factors, as well as in cognitive function. The P300 event-related potential has been established as a predictor of cognitive decline. We decided to determine if this measure, as well as 2 standard tests of memory and attention, may be correlated with serum levels of sex hormones and growth factors, and if there are any generalizations that could be made based on these parameters and the aging process. Findings In this large clinically based preliminary study several sex-stratified associations between hormone levels and cognition were observed, including (1) for males aged 30 to 49, both IGF-1 and IGFBP-3 significantly associated negatively with prolonged P300 latency; (2) for males aged 30 to 49, the spearman correlation between prolonged P300 latency and low free testosterone was significant; (3) for males aged 60 to 69, there was a significant negative correlation between P300 latency and DHEA levels; (4) for females aged 50 to 59 IGFBP-3 significantly associated negatively with prolonged P300 latency; (5) for females at all age periods, estrogen and progesterone were uncorrelated with P300 latency; and (6) for females aged 40 to 69, there was significant negative correlation between DHEA levels and P300 latency. Moreover there were no statistically significant correlations between any hormone and Wechsler Memory Scale-III (WMS-111). However, in females, there was a significant positive correlation between estrogen levels and the number of Attention Deficit Disorder (ADD) complaints. Conclusion Given certain caveats including confounding factors involving psychiatric and other chronic diseases as well as medications, the results may still have important value. If these results could be confirmed in a more rigorously controlled investigation, it may have important value in the diagnosis, prevention and treatment of cognitive impairments and decline.

We obtain new explicit exponential stability results for difference equations with several variable delays and variable coefficients. Several known results, such as Clark's asymptotic stability criterion, are generalized and extended to a new class of equations.

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine., Competing Interests: Declaration of Competing Interest KB and ERB are members of the Kenneth Blum Behavioral and Neurogenetic Institute. KB is the inventor of the GARS test to measure hypodopaminergia in patients and the general public and precision Pro-dopamine regulation. He is credited with both domestic and foreign patents licensed to iVitalize. There are no other conflicts of interest to report., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: In this genomic era of addiction medicine, ideal treatment planning begins with genetic screening to determine neurogenetic antecedents of the Reward Deficiency Syndrome (RDS) phenotype. Patients suffering from endotype addictions, both substance and behavioral, and other mental health/comorbid disorders that share the neurobiological commonality of dopamine dysfunction, are ideal candidates for RDS solutions that facilitate dopamine homeostasis, addressing the cause, rather than symptoms., Objective: Our goal is to promote the interplay of molecular biology and recovery as well as provide evidence linked to RDS and its scientific basis to primary care physicians and others., Methods: This was an observational case study with a retrospective chart review in which an RDS treatment plan that utilized Genetic Addiction Risk Severity (GARS) analysis to evaluate neurogenetic challenges was used in order to develop appropriate short- and long-term pharmaceutical and nutraceutical interventions., Results: A Substance Use Disorder (SUD) treatment-resistant patient was successfully treated utilizing the GARS test and RDS science., Conclusion: The RDS Solution Focused Brief Therapy (RDS-SFBT) and the RDS Severity of Symptoms Scale (SOS) may provide clinicians with a useful tool for establishing neurological balance and helping patients to achieve self-efficacy, self-actualization, and prosperity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The COVID-19 pandemic has accelerated neurological, mental health disorders, and neurocognitive issues. However, there is a lack of inexpensive and efficient brain evaluation and screening systems. As a result, a considerable fraction of patients with neurocognitive or psychobehavioral predicaments either do not get timely diagnosed or fail to receive personalized treatment plans. This is especially true in the elderly populations, wherein only 16% of seniors say they receive regular cognitive evaluations. Therefore, there is a great need for development of an optimized clinical brain screening workflow methodology like what is already in existence for prostate and breast exams. Such a methodology should be designed to facilitate objective early detection and cost-effective treatment of such disorders. In this paper we have reviewed the existing clinical protocols, recent technological advances and suggested reliable clinical workflows for brain screening. Such protocols range from questionnaires and smartphone apps to multi-modality brain mapping and advanced imaging where applicable. To that end, the Society for Brain Mapping and Therapeutics (SBMT) proposes the Brain, Spine and Mental Health Screening (NEUROSCREEN) as a multi-faceted approach. Beside other assessment tools, NEUROSCREEN employs smartphone guided cognitive assessments and quantitative electroencephalography (qEEG) as well as potential genetic testing for cognitive decline risk as inexpensive and effective screening tools to facilitate objective diagnosis, monitor disease progression, and guide personalized treatment interventions. Operationalizing NEUROSCREEN is expected to result in reduced healthcare costs and improving quality of life at national and later, global scales.

We stabilize a prescribed cycle or an equilibrium of a difference equation using pulsed stochastic control. Our technique, inspired by Kolmogorov's law of large numbers, activates a stabilizing effect of stochastic perturbation and allows for stabilization using a much wider range for the control parameter than would be possible in the absence of noise. Our main general result applies to both prediction-based and target-oriented controls. This analysis is the first to make use of the stabilizing effects of noise for prediction-based control; the stochastic version has previously been examined in the literature, but only the destabilizing effect of noise was demonstrated. A stochastic variant of target-oriented control has never been considered, to the best of our knowledge, and we propose a specific form that uses a point equilibrium or one point on a cycle as a target. We illustrate our results numerically on the logistic, Ricker, and Maynard Smith models from population biology.

The purpose of this retrospective study was to identify the coexisting factors for EIR and to characterise EIR clinically and demographically. All cases of EIR that were referred to the endodontic department between 2011 to 2016 and diagnosed by an endodontist were evaluated. Demographic and clinical characteristics were collected and evaluated. Thirty-eight cases of EIR diagnosed between 2011 and 2016 were included in the study. Seventy-one percent of EIR cases were misdiagnosed by general practitioners. The most affected teeth were the maxillary central incisors (29% of cases) and mandibular molars (26%). Sixty-eight percent of EIR cases were diagnosed in teeth with clinically normal pulp. Pulp necrosis was observed mainly in the advanced stages (class 3 and class 4) of EIR (75%) and in teeth with a history of trauma (63%). Histories of previous trauma and orthodontic treatment were reported in 29% and 23% of cases, respectively., (© 2018 Australian Society of Endodontology Inc.)

The paper explores the influence of harvesting (or culling) on the outcome of the competition of two species in a spatially heterogeneous environment. The harvesting effort is assumed to be proportional to the space-dependent intrinsic growth rate. The differences between the two populations are the diffusion strategy and the harvesting intensity. In the absence of harvesting, competing populations may either coexist, or one of them may bring the other to extinction. If the latter is the case, introduction of any level of harvesting to the successful species guarantees survival to its non-harvested competitor. In the former case, there is a strip of "close enough" to each other harvesting rates leading to preservation of the original coexistence. Some estimates are obtained for the relation of the harvesting levels providing either coexistence or competitive exclusion., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The United States are amid an opioid overdose epidemic; we are challenged to provide non-addicting/non-pharmacological alternatives to assist in pain attenuation. There are proven strategies available to manage chronic pain effectively without opioids. Utilization review providers for insurance companies often ignore medicine based scientific peer-reviewed studies that warn against the chronic use of opioid medications, as well as the lack of evidence to support long-term use of opioids for pain. This paradigm must change if we are to indeed change the drug-embracing culture in American chronic pain management. A barrier to treatment is pushback on the part of insurance companies especially as it relates to fighting against pain relief alternatives compared to classical analgesic agents. Pain specialists in the U.S., are compelled to find alternative solutions to help pain victims without promoting unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain." It is noteworthy that reward center of the brain plays a crucial role in the modulation of nociception, and that adaptations in dopaminergic circuitry may affect several sensory and affective components of chronic pain syndromes. Possibly knowing a patient's genetic addiction risk score (GARS™) could eliminate guessing as it relates to becoming addicted., Competing Interests: Conflict of Interests K. Blum is 100% owner of Synaptamine Inc. holding a number of nutrigenomic patents worldwide including Geneus Health holding genetic testing for RDS. All other authors have no conflict of interest to report.

In contrast with unstructured models, structured discrete population models have been able to fit and predict chaotic experimental data. However, most of the chaos control techniques in the literature have been designed and analyzed in a one-dimensional setting. Here, by introducing target-oriented control for discrete dynamical systems, we prove the possibility to stabilize a chosen state for a wide range of structured population models. The results are illustrated with introducing a control in the celebrated LPA model describing a flour beetle dynamics. Moreover, we show that the new control allows to stabilize periodic solutions for higher-order difference equations, such as the delayed Ricker model, for which previous target-oriented methods were not designed.

With aging, there is decline in both short-term and long-term memory. This effect is magnified by epigenetic insults on specific, dopamine- related genes (e.g., DRD2, DAT1) as well as by impaired or reduced mRNA transcription. In addition, long-term memory ability is positively correlated with dopamine function and there is evidence that aging is associated with a reduction in brain dopamine D2 receptors, with an acceleration seen in aging-induced dementia. As a result, the authors tested the acute effect of a Pro-Dopamine Regulator (KB220Z, liquid Nano variant) on an aspect of long-term memory performance in a 77-year-old, highly functional male, using the Animal Naming Test (ANT). An improvement in long-term memory retrieval had initially been noted during the subject's follow-up neurology exam, after he had been, for other reasons, taking KB220z. The patient had been given a number of ANTs by his primary and, later, another neurologist, from 2013 to 2016. Because the number of ANT observations was small (N = 7 with two groups) and the data uncorrelated, a non-parametric Wilcoxon-Mann-Whitney test was performed to test mean differences. After KB220z, the patient had much higher scores (p = 0.04762) on the ANT vs. when not taking it. His scores increased from the 30 th percentile (pre-test) to the 76 th percentile, after the first administration of KB220z and, later, to the 98 th percentile, after a second administration of KB220z, six months later. The results indicate that KB220z, given acutely, increased a form of long-term memory retrieval in a highly functional, elderly male. Larger, double-blind, randomized controlled studies are encouraged., Competing Interests: Disclosure There are no other conflicts.

For three different types of angiogenesis models with variable delays, we consider either continuous or impulse therapy that eradicates tumor cells and suppresses angiogenesis. For the cancer-free solution, explicit conditions of global stability for the continuous and impulsive systems are obtained, together with delay-dependent estimates for the rates of decay for the tumor volume and pathological angiogenesis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Investigating a method of chaos control for one-dimensional maps, where the intervention is proportional to the difference between a fixed value and a current state, we demonstrate that stabilization is possible in one of the two following cases: (1) for small values, the map is increasing and the slope of the line connecting the points on the line with the origin is decreasing; (2) the chaotic map is locally Lipschitz. Moreover, in the latter case we prove that any point of the map can be stabilized. In addition, we study pulse stabilization when the intervention occurs each m-th step and illustrate that stabilization is possible for the first type of maps. In the context of population dynamics, we notice that control with a positive target, even if stabilization is not achieved, leads to persistent solutions and prevents extinction in models which experience the Allee effect.

Addictions to smoking, alcohol, illicit drugs, and certain behaviors like gambling, overeating, and sex, are prevalent worldwide. These behaviors are highly destructive and costly to individuals and society due to health consequences, criminality and lost productivity. The genetic vulnerability, environmental exposures, and individual behaviors that contribute to the brain dysfunction and compulsive tendencies that mark addiction make it one of the most complicated diseases to study and treat. Although much has been learned about the genetic basis of and biochemical imbalances associated with the addictions, research leading to effective treatments has been slow. Addictions are often accompanied by an inner sense of disintegration, enslavement and meaninglessness that can be viewed in terms of a spiritual craving for wholeness, freedom, and transformation. Arguably, progress towards effective treatment has been retarded by insufficient attention being paid to understanding the role of spirituality in helping to heal addicts. Assuming one accepts the belief that the brain mediates all conscious and unconscious experiences- including spiritually experiences -healing, like addictions, can be related to the processes by which the human brain is organized for controlling pleasure and pain. Here we hypothesize that a healthy spirituality may come more naturally to some individuals because of the unique interaction of their genes and their environments, and we review the evidence in support of this view.

This article co-authored by a number of scientists, ASAM physicians, clinicians, treatment center owners, geneticists, neurobiologists, psychologists, social workers, criminologists, nurses, nutritionist, and students, is dedicated to all the people who have lost loved ones in substance-abuse and "reward deficiency syndrome" related tragedies. Why are we failing at reducing the incidence of 'Bad Behaviors'? Are we aiming at the wrong treatment targets for behavioral disorders? We are proposing a paradigm shift and calling it "Reward Deficiency Solution System" providing evidence for its adoption.

Over time, based on evidence-based medicine, a number of hormonal test levels including IGF-1 had been raised or lowered to meet new criteria standards. In particular, IGF-1 plasma levels have been shown in several studies to be an independent diagnostic tool in Adult Growth Hormone Deficiency (AGHD). Many endocrinology studies link low IGF-1 plasma levels with low levels of other anterior pituitary hormones (i.e., LH, FSH, and TSH). Low IGF-1 is considered by most to be between 84-100 µ/l and numerous studies recommend that raising IGF-1 to high normal range reverses Chronic Medical Diseases (CMD), improves bone mineral density (BMD), and fibromyalgia. Moreover, some studies suggest that low levels of IGF-1 by itself independent of anterior pituitary deficiencies is sufficient to determine AGHD in humans. In order to determine the relationship of low IGF-1 with that of LH, FSH, and TSH levels in subjects with CMD, we evaluated these levels (± SD) in 944 patients. Patients with IGF-1 below 84 µ/l, 100 µ/l, and 150 µ/l were accessed. 9.22% had less than 84 µ/l (SD ± 12.52); 19.9% had less than 100 µ/l (SD ± 9.54); and 51.6 had less than 150 µ/l (SD ± 26.0). Specifically, the percentages found for low LH, FSH, and TSH were only 4.2%, 4.8%, and 6.5%. We conclude that IGF-1 deficiencies occur independent of comorbid deficiencies of LH, FSH, and TSH. Finally, we propose that based on the present investigation, IGF-1 low levels between the range of 84-100 µ/l may be too low to be considered as an independent diagnostic marker to treat AGHD with CMD.

Now after many years of successful bariatric (weight-loss) surgeries directed at the obesity epidemic clinicians are reporting that some patients are replacing compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. This review article explores evidence from psychiatric genetic animal and human studies that link compulsive overeating and other compulsive disorders to explain the phenomenon of addiction transfer. Possibly due to neurochemical similarities, overeating and obesity may act as protective factors reducing drug reward and addictive behaviors. In animal models of addiction withdrawal from sugar induces imbalances in the neurotransmitters, acetylcholine and dopamine, similar to opiate withdrawal. Many human neuroimaging studies have supported the concept of linking food craving to drug craving behavior. Previously our laboratory coined the term Reward Deficiency Syndrome (RDS) for common genetic determinants in predicting addictive disorders and reported that the predictive value for future RDS behaviors in subjects carrying the DRD2 Taq A1 allele was 74%. While poly genes play a role in RDS, we have also inferred that disruptions in dopamine function may predispose certain individuals to addictive behaviors and obesity. It is now known that family history of alcoholism is a significant obesity risk factor. Therefore, we hypothesize here that RDS is the root cause of substituting food addiction for other dependencies and potentially explains this recently described Phenomenon (addiction transfer) common after bariatric surgery.

Unlabelled: Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the "brain reward cascade," a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH])., Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members., Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants., Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific "reward" phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.

As the growth rate parameter increases in the Ricker, logistic and some other maps, the models exhibit an irreversible period doubling route to chaos. If a constant positive perturbation is introduced, then the Ricker model (but not the classical logistic map) experiences period doubling reversals; the break of chaos finally gives birth to a stable two-cycle. We outline the maps which demonstrate a similar behavior and also study relevant discrete spatial models where the value in each cell at the next step is defined only by the values at the cell and its nearest neighbors. The stable 2-cycle in a scalar map does not necessarily imply 2-cyclic-type behavior in each cell for the spatial generalization of the map., ((c) 2010 American Institute of Physics.)

Prediction of accurate and meaningful force sharing among synergistic muscles is a major problem in biomechanics research. Given a resultant joint moment, a unique set of muscle forces can be obtained from this mathematically redundant system using nonlinear optimization. The classical cost functions for optimization involve a normalization of the muscle forces to the absolute force capacity of the target muscles, usually by the cross-sectional area or the maximal isometric force. In a one degree of freedom model this leads to a functional relationship between moment arms and the predicted muscle forces, such that for constant moment arms, or constant ratios of moment arms, agonistic muscle forces increase or decrease in unison. Experimental studies have shown however that the relationship between muscle forces is highly task-dependent often causing forces to increase in one muscle while decreasing in a functional agonist, likely because of the contractile conditions and contractile properties of the involved muscles. We therefore, suggest a modified cost function that accounts for the instantaneous contraction velocity of the muscles and its effect on the instantaneous maximal force. With this novel objective function, a task-dependent prediction of muscle force distribution is obtained that allows, even in a one degree of freedom system, the prediction of force sharing loops, and simultaneously increasing and decreasing forces for agonist pairs of muscles.

While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.

We consider both autonomous and nonautonomous population models subject to either impulsive or continuous harvesting. It is demonstrated in the paper that the impulsive strategy can be as good as the continuous one, but cannot outperform it. We introduce a model, where certain harm to the population is incorporated in each harvesting event, and study it for the logistic and the Gompertz laws of growth. In this case, impulsive harvesting is not only the optimal strategy but is the only possible one.

A class of linearly perturbed discrete-time single species scramble competition models, like the Ricker map, is considered. Perturbations can be of both recruitment and harvesting types. Stability (bistability) is considered for models, where parameters of the map do not depend on time. For models with recruitment, the result is in accordance with Levin and May conjecture [S.A. Levin, R.M. May, A note on difference delay equations, Theor. Pop. Biol. 9 (1976) 178]: the local stability of the positive equilibrium implies its global stability. For intrinsic growth rate r-->infinity the way to chaos is broken down to get extinction of population for the depletion case and to establish a stable two-cycle period for models with immigration. The latter behaviour is also studied for models with random discrete constant perturbations of recruitment type. Extinction, persistence and existence of periodic solutions are studied for the perturbed Ricker model with time-dependent parameters.

Although situational judgment tests have a long history in the psychological assessment literature and continue to be frequently used in employment contexts, there has been virtually no summarization of this literature. The purpose of this article is to review the history of such tests and present the results of a meta-analysis on criterion-related and construct validity. On the basis of 102 coefficients and 10,640 people, situational judgment tests showed useful levels of validity (rho = .34) that were generalizable. A review of 79 correlations between situational judgment tests and general cognitive ability involving 16,984 people indicated that situational judgment tests typically evidence relationships with cognitive ability (rho = .46). On the basis of the literature review and meta-analytic findings, implications for the continued use of situational judgment tests are discussed, particularly in terms of recent investigations into tacit knowledge.

Ambras syndrome (AMS) is a unique form of congenital universal hypertrichosis. The syndrome has been found in association with rearrangements of chromosome 8 in two isolated cases. One of these patients was reported to have an apparently balanced paracentric inversion of chromosome 8, inv(8)(q12q22). Our cytogenetic analysis on this patient showed that the rearrangement of chromosome 8 is more complex than initially reported. We detected an insertion of the q23-q24 region into a more proximal region of the long arm of chromosome 8 as well as a large deletion in 8q23:46,XX, rea(8)(8pter-->8q13::8q23.2-->8q24.1::8q13-->8q23.1::8q24.1-->8qter). Given the large number of breakpoints and the presence of a substantial deletion, it is surprising that the proposita did not show anomalies other than these characteristic of Ambras syndrome., (Copyright 2001 Wiley-Liss, Inc.)

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this hypodopaminergic trait under the rubric of a reward deficiency syndrome.

This is the first report in humans of the effects of daily ingestion of a specific amino acid mixture, Kantroll, on cognitive event-related potentials (ERPs) associated with performance. Cognitive ERPs were generated by two computerized visual attention tasks, the Spatial Orientation Task (SOT) and Contingent Continuous Performance Task (CCPT), in normal young adult volunteers, where each subject acted as his own control for testing before and after 28-30 days of amino acid ingestion. A statistically significant amplitude enhancement of the P300 component of the ERPs was seen after Kantroll for both tasks, as well as improvement with respect to cognitive processing speeds. The enhancement of neurophysiologic function observed in this study on normal controls is consistent with the facilitation of recovery of individuals with RDS (i.e., substance use disorder, ADHD, carbohydrate bingeing) following the ingestion of the amino acid supplement, Kantroll, and warrants additional placebo-controlled, double-blind, studies to confirm and extend these results.

In order to investigate the prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with and without comorbid substance use disorder, a total of 40 patients, from an outpatient neuropsychiatric clinic in Princeton, New Jersey, were genotyped for presence or absence of the Taq I DRD2 A1 allele. The primary inclusion criterion for 40 obese subjects was a body mass index (BMI) equal to or over 25 (uncharacterized); 11 obese subjects had severe substance use disorder; 20 controls had a BMI below 25; and, 33 substance use disorder (less severe) patients had a BMI below 25. The data were statistically compared with three different sets of controls divided into three separate groups (Group I, n = 20; Group II, n = 286; Group III, n = 714). They differed according to screening criteria (drug, alcohol, nicotine abuse/dependence, BMI below 25 and other related behaviours including parental history of alcoholism or drug abuse and DSM IV, Axis I and Axis II diagnoses). Groups II and III were population controls derived from the literature. The prevalence of the Taq I A1D2 dopamine receptor (DRD2) alleles was determined in 40 Caucasian obese females and males. In this sample with a mean BMI of 32.35 +/- 1.02, the A1 allele of the DRD2 gene was present in 52.5% of these obese subjects. Furthermore, we found that in the 23 obese subjects possessing comorbid substance use disorder, the prevalence of the DRD2 A1 allele significantly increased compared to the 17 obese subjects without comorbid substance use disorder. The DRD2 A1 allele was present in 73.9% of the obese subjects with comorbid substance use disorder compared to 23.5% in obese subjects without comorbid substance use disorder. Moreover, when we assessed severity of substance usage (alcoholism, cocaine dependence, etc.) increasing severity of drug use increased the prevalence of the Taq I DRD2 A1 allele; where 66.67% (8/12) of less severe probands possessed the A1 allele compared to 82% (9/11) of the most severe cases. Linear trend analyses showed that increasing use of drugs was positively and significantly associated with A1 allelic classification (p < 0.00001). These preliminary data suggest that the presence of the DRD2 A1 allele confirms increased risk not only for obesity, but also for other related addictive behaviours (previously referred to as the Reward Deficiency Syndrome) and that a BMI over 25 by itself (without characterization of macroselection or comorbid substance use disorders) is not a sufficient criterion for association with the DRD2 A1 allele.

Objective: To assess by brain electrical activity mapping whether cocaine and alcohol abuse and dependence would exacerbate electro-physiological abnormalities in a psychiatrically-ill population., Design, Setting, and Participants: Utilizing a brain mapping system, we assessed EEG, Spectral Analysis (Quantitative EEG[QEEG]). Evoked Potentials (Auditory and Visual), and P300 (cognitive evoked potential), in a total of 111 probands divided into three groups: controls (N = 16), psychiatrically-ill without comorbid substance use disorder (N = 34), and psychiatrically-ill with comorbid substance use disorder (cocaine and alcohol abuse and dependence) (N = 61), at an outpatient neuropsychiatric clinic. With regard to demographic data, the group participating in this study did not differ significantly. A comparison was made among the groups to assist in differentiating the effects of substance use disorder compared to psychiatric disease on brain electrical activity., Main Outcome Measures: An assessment of electrophysiological abnormalities and their brain location in psychiatric and substance use disorder patients was done with a brain electrical activity mapping test., Main Results: Among the non-substance use disorder, psychiatrically-ill (PI) and substance use disorder, psychiatrically-ill (PI/SD) groups, significantly different brain map abnormalities were observed relative to an assessed normal population MANOVA (P = .017). Moreover, with regard to Spectral Analysis, ANOVA was significant at a P = .038, and we found a weighted linear trend of increased abnormal total spectral analysis (P = .0113), whereby substance use was significantly worse than controls. Moreover among the PI and PI/SD groups, significantly greater total evoked potential (EP) brain trap abnormalities were observed when compared with a characterized normal population (P = .0023) with increasing abnormalities as a function of substance use disorder as measured by a weighted linear trend (P = .0022). In order to determine the site of the EPS abnormalities, we evaluated these abnormalities by location. In this regard, we found all temporal abnormalities (AVBITA, see Table 2) among the PI and PI/SD groups to be significantly greater relative to an assessed normal population (P = .0026). Furthermore, we observed a linear trend of increased temporal abnormalities with increasing substance use disorder (P < .0008). In terms of bitemporal abnormalities (AVBIT) among the PI and PI/SD groups, we also found significantly more bitemporal lobe abnormalities in the PI/SD group compared to our control population (P = .009). Additionally, a weighted linear trend of increased abnormal bitemporal lobe abnormalities was observed with increasing substance use disorder (P = .0022). In the frontal lobe similar findings were observed. With AVBIFA the ANOVA was P < .011, with a weighted linear trend of P < .005 and the PI/SD group were significantly more abnormal than PI or CS on a Duncan Range test. It is noteworthy that in a selected group of depressed (Major Depressive Disorder Recurrent, 296.3) patients, we found profound abnormalities in the various brain map parameters tested. MANOVA and Univariate ANOVA's revealed significantly greater abnormalities in the PI and PI/SD groups compared to assessed controls. A MANOVA for total brain abnormalities was significant at P = .043 and univariate ANOVA's for composite measurements of TSA (P = .017), EPS (P = .0002), AVBITA (P = .000015), and AVBIT (P < .00002) are also significant. With regard to EPS and AVBITA a weighted linear trend was observed where there were increasing abnormalities with increasing substance use disorder, P = .0001 and P = .000003, respectively. Most importantly we found that in addition to increased abnormalities with increasing substance use disorder the PI/SD group had significantly more abnormalities compared to the PI group with regard to both the TSA (P < .05) and AVBIT (P < .05) composite parameters as meas

Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.

The dopaminergic system, and in particular the dopamine D2 receptor, has been profoundly implicated in reward mechanisms in the meso-limbic circuitry of the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance (alcohol, drug, tobacco and food) seeking behavior. Decades of research indicate that genetics play an important role in vulnerability to severe substance seeking behavior. We propose that variants of the D2 dopamine receptor gene are important common genetic determinants in predicting compulsive disease.

The role of the dopaminergic system in P300 has been implicated and previous studies have suggested the presence of a heritable component in the genesis of P300 or P3, a late positive component of the event-related potential. In the present investigation, 155 Caucasian male and female diagnosed neuropsychiatrically-ill patients with and without comorbid drug and alcohol abuse/dependence were genotyped for the presence or absence of the A1 allele of the D2 dopamine receptor gene (DRD2). The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between all groups studied with A1 and A2 allele carriers. However, we now report prolonged P3 latency in neuropsychiatrically-ill patients (with or without polysubstance abuse) with those carrying two copies of the A1 allele (homozygote) of the DRD2 gene (quadratic trend, p = 0.01). Moreover, the age-adjusted mean P3 latency in the D2A2/A2 allele group was 327.8 +/- 3.08 ms compared by ANOVA, to 360.04 +/- 4.86 ms in the D2A1/A1 group. Our work suggests an association of polymorphisms of the DRD2 gene and a biological marker previously indicated to have predictive value in vulnerability to substance abuse.