Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Returning home: forced conscription, reintegration, and mental health status of former abductees of the Lord's Resistance Army in northern Uganda

<p>Abstract</p> <p>Background</p> <p>Since the late 1980s, the Lord's Resistance Army (LRA), a spiritualist rebel group in northern Uganda, has killed and mutilated thousands of civilians and abducted an estimated 52,000 to 75,000 people to serve as soldiers, porters, and sex slaves for its commanders. This study examines the types of violence to which former abductees have been exposed and the extent to which these acts have affected their psychological well-being.</p> <p>Methods</p> <p>This is a cross-sectional study of 2,875 individuals selected through a multi-stage stratified cluster sampling design conducted in 8 districts of northern Uganda. Multivariate logistic regressions were performed with symptoms for Post-traumatic Stress Disorder (PTSD) and depression as the main outcome measures.</p> <p>Results</p> <p>One-third of the respondents (33%) self-reported having experienced abduction (49% among the Acholi, the largest tribal group in northern Uganda). Over half (56%) of all the respondents and over two-thirds of those who experienced abduction met the criteria for symptoms of post-traumatic stress disorder (PTSD). Multivariate analysis shows that several factors increased the risk of former LRA abductees developing symptoms of PTSD. These factors included gender (females were more susceptible than males), being a member of the Acholi ethnic group, participating in or witnessing a cumulative number of traumatic events, and encountering difficulties re-integrating into communities after abduction. Factors associated with increased risk of meeting criteria for symptoms of depression included older age of males at the time of abduction, lower score on social relationship scale, high incidence of general traumatic event exposure, high incidence of forced acts of violence, and problems reintegrating into communities after abduction.</p> <p>Conclusion</p> <p>Abduction and forced conscription of civilians has affected the psychological well-being of a significant number of northern Ugandans. The sources of psychological trauma are multiple, ranging from witnessing to being forced to commit violent acts, and compounded by prolonged exposure to violence, often for months or years. Community-based mental health care services and reintegration programs are needed to facilitate the reintegration of former abductees back into their communities.</p

Effects of acute tryptophan depletion on affective processing in first-degree relatives of depressive patients and controls after exposure to uncontrollable stress

Rationale Individuals with a family history of depression may be more likely to develop depression due to an innate vulnerability of their serotonergic system. However, even though serotonergic vulnerability may constitute a risk factor in the development of depression, it does not seem to be sufficient to cause a depressive episode. Based on previous data, it is suggested that stress may be a mediating factor. Objectives This study examined the role of serotonin (5-HT) in stress coping in individuals with or without a family history of depression. Materials and methods Nineteen healthy first-degree relatives of depressive patients (FH+) and 19 healthy controls without a family history of depression (FH-) were tested in a double-blind placebo-controlled design for affective processing under acute stress exposure, following acute tryptophan depletion (ATD) or placebo. Results Significant negative effects were found of stress on affective processing in FH- and FH+. In addition, FH- responded slower to positive words after stress only following ATD, whereas FH+ responded marginally slower under stress already after placebo and before stress following ATD. Conclusion Acute stress exposure reduces positive affective bias; supporting the role of stress as an important predecessor in the development of depression. Furthermore, FH+ may be more susceptible than FH- to the negative effects of stress as well as to the negative effects of ATD. The results support the assumption that the 5-HT system is involved in stress resilience and may be more vulnerable in first-degree relatives of depression

Business process modelling to improve incident management process

Business process management (BPM) is an approach focused on the continuous improvement of business processes, providing for this a collection of best practices. These best practices enable the redesign of business processes to meet the desired performance. IT service management (ITSM) defines the management of IT operations as a service. There are several ITSM frameworks available, consisting in best practices that propose standardizing these pro- cesses for the respective operations. By adopting these frameworks, organisations can align IT with their business objectives. Therefore, the objective of this research is to understand how BPM can be used to improve of ITSM processes. An exploratory case study in a multinational company based in Lisbon, Portugal, is conducted for the improvement of the time performance of an inci- dent management process. Data were gained through documentation, archival records, interviews and focus groups with a team involved in IT support service. So far, the as-is process was elicited, and respective incongruences clarified. During the next months the authors intend to identify the main problems and simulate the appropriate BPM heuristics to understand the impact in the busi- ness organisation.info:eu-repo/semantics/acceptedVersio

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Evolution of response dynamics underlying bacterial chemotaxis

© 2011 Soyer and Goldstein; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The ability to predict the function and structure of complex molecular mechanisms underlying cellular behaviour is one of the main aims of systems biology. To achieve it, we need to understand the evolutionary routes leading to a specific response dynamics that can underlie a given function and how biophysical and environmental factors affect which route is taken. Here, we apply such an evolutionary approach to the bacterial chemotaxis pathway, which is documented to display considerable complexity and diversity.Results: We construct evolutionarily accessible response dynamics starting from a linear response to absolute levels of attractant, to those observed in current-day Escherichia coli. We explicitly consider bacterial movement as a two-state process composed of non-instantaneous tumbling and swimming modes. We find that a linear response to attractant results in significant chemotaxis when sensitivity to attractant is low and when time spent tumbling is large. More importantly, such linear response is optimal in a regime where signalling has low sensitivity. As sensitivity increases, an adaptive response as seen in Escherichia coli becomes optimal and leads to 'perfect' chemotaxis with a low tumbling time. We find that as tumbling time decreases and sensitivity increases, there exist a parameter regime where the chemotaxis performance of the linear and adaptive responses overlap, suggesting that evolution of chemotaxis responses might provide an example for the principle of functional change in structural continuity.Conclusions: Our findings explain several results from diverse bacteria and lead to testable predictions regarding chemotaxis responses evolved in bacteria living under different biophysical constraints and with specific motility machinery. Further, they shed light on the potential evolutionary paths for the evolution of complex behaviours from simpler ones in incremental fashion

Proctitis following stereotactic body radiation therapy for prostate cancer

Background Proctitis after radiation therapy for prostate cancer remains an ongoing clinical challenge and critical quality of life issue. SBRT could minimize rectal toxicity by reducing the volume of rectum receiving high radiation doses and offers the potential radiobiologic benefits of hypofractionation. This study sought to evaluate the incidence and severity of proctitis following SBRT for prostate cancer. Methods Between February 2008 and July 2011, 269 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. All patients were treated to 35-36.25Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Rectal bleeding was recorded and scored using the CTCAE v.4. Telangiectasias were graded using the Vienna Rectoscopy Score (VRS). Proctitis was assessed via the Bowel domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at 1, 3, 6, 9, 12, 18 and 24 months post-SBRT. Results The median age was 69 years with a median prostate volume of 39 cc. The median follow-up was 3.9 years with a minimum follow-up of two years. The 2-year actuarial incidence of late rectal bleeding ≥ grade 2 was 1.5%. Endoscopy revealed VRS Grade 2 rectal telangiectasias in 11% of patients. All proctitis symptoms increased at one month post-SBRT but returned to near-baseline with longer follow-up. The most bothersome symptoms were bowel urgency and frequency. At one month post-SBRT, 11.2% and 8.5% of patients reported a moderate to big problem with bowel urgency and frequency, respectively. The EPIC bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 6 months and 18 months before returning to near-baseline at two years post-SBRT. Prior to treatment, 4.1% of men felt their bowel function was a moderate to big problem which increased to 11.5% one month post-SBRT but returned to near-baseline at two years post-SBRT. Conclusions In this single institution cohort, the rate and severity of proctitis observed following SBRT is low. QOL decreased on follow-up; however, our results compare favorably to those reported for patients treated with alternative radiation modalities. Future prospective randomized studies are needed to confirm these observations