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The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice
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DOI: 10.1007/s00125-012-2696-9
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- Pardo, F.N., Altirriba, J., Pradas-Juni, M. et al. Diabetologia (2012) 55: 3331. doi:10.1007/s00125-012-2696-9
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Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function.
Rkip1 (also known as Pebp1) knockout (Rkip1−/−) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1−/− mice after streptozotocin treatment.
Rkip1−/− mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1−/− mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice.
These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration.
KeywordsBeta cell Diabetes Insulin Neonatal beta cell growth Proliferation Raf-1 RKIP
Extracellular signal-regulated kinase
Glycogen synthase kinase 3
Intraperitoneal glucose tolerance test
Mitogen-activated protein kinase
MAP kinase kinase
- NF-κB
Nuclear factor κB
Postnatal day
Platelet-derived growth factor
Raf-1 kinase inhibitor protein 1
Wild type
Type 2 diabetes results from pancreatic beta cell failure on a background of insulin resistance. To compensate for the increased insulin demand in insulin-resistant states, beta cells augment their insulin biosynthetic and secretory capacity in part by expanding their mass through hyperplastic and hypertrophic mechanisms [1]. However, when beta cells reach their maximum compensatory response and can no longer overcome insulin resistance, overt diabetes occurs. Hence, understanding how beta cells regulate their growth could lead to the development of therapeutic approaches to prevent and/or delay the onset of this disease.
During the last few years, our group has been investigating the actions of sodium tungstate on beta cell plasticity. We have shown that this agent can normalise blood glucose levels in streptozotocin (STZ)-treated rats and that this normalisation correlates with increased beta cell proliferation and neogenesis [2, 3, 4]. Recently, in a global transcriptome analysis, we identified the gene encoding the Raf-1 kinase inhibitor protein 1 (RKIP1) as one of the potential candidate genes involved in the ability of tungstate to modulate pancreatic beta cell mass [5].
RKIP1 is an evolutionarily conserved protein that was first recognised as a regulator of the MAPK signal transduction cascade through its interaction and inhibition of Raf-1 kinase activity [6]. However, upon phosphorylation by protein kinase C, RKIP1 can dissociate from Raf-1 and inhibit G protein-coupled receptor kinase 2 (GRK2) [7], a negative regulator of G protein-coupled receptors. Additionally, RKIP1 has been implicated as a negative regulator of nuclear factor κB (NF-κB)-signalling pathways and an activator of glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways [8, 9]. Therefore, RKIP1 mediates the crosstalk between various important cellular signalling pathways and, consequently, can influence a wide array of cellular functions including cell proliferation, differentiation and apoptosis. Thus, RKIP1 has been implicated in cancer, neurological functioning and reproduction (reviewed in [10, 11, 12]).
In the pancreas, RKIP1 is present at high levels in islets, whilst its presence in exocrine cells is somewhat controversial [13, 14]. The role of RKIP1 in beta cells is not fully understood. Because modulation of RKIP1 levels in the beta cell line HIT-T15 influences MAPK signalling and cell proliferation, it has been speculated that the presence of high amounts of RKIP1 in adult beta cells could partially explain the low proliferative capacity of these cells [13]. In line with this, overproduction of Raf-1 kinase in primary beta cells enhances cell proliferation [15]. Conversely, Raf-1 kinase inhibition results in increased beta cell apoptosis, indicating that modulation of this pathway may also contribute to beta cell survival [16]. Taken together, this in vitro evidence supports a possible role of RKIP1 in the modulation of pancreatic beta cell plasticity.
The aim of the present study was to investigate the involvement of RKIP1 in the regulation of beta cell mass using mice with a homozygous germ-line deletion of the Rkip1 gene (Rkip1−/−). The phenotypes of Rkip1−/− mice described to date include age-dependent learning and olfaction deficits and fertility defects within the males [12, 17]. Here we have characterised pancreatic morphology and glucose homeostasis in Rkip1−/− and provide evidence of a role of RKIP1 as a negative regulator of beta cell mass under physiological (normal growth) and pathological (STZ-induced diabetes) conditions in vivo.
Mouse studies
Rkip1−/− mice were generously provided by Dr Jan Klysik (Brown University, Providence, Rhode Island, USA), maintained in a C57BL/6 background and genotyped as described previously [17]. Protocols were approved by the Animal Ethics Committee of the University of Barcelona and the Principles of Laboratory Animal Care were followed. Diabetes was induced by intraperitoneal injection of 100 mg/kg STZ (Sigma-Aldrich, St Louis, MO, USA) in adult mice weighing 18–22 g that were fasted for 6 h. Blood glucose levels were measured weekly until the time they were killed.
For intraperitoneal glucose tolerance tests (IPGTTs), mice fasted for 6 h were injected with 2 g glucose/kg body weight. Blood samples were collected at 0, 15, 30, 60 and 120 min after injection and glycaemia was measured using a clinical glucometer and Accu-Chek test strips (Roche, Basel, Switzerland). Plasma was separated by centrifugation and kept at −80°C for insulin determination. For insulin tolerance tests, animals were injected with 0.75 U insulin/kg body weight. Blood samples were collected at 0, 15, 30 and 60 min and glucose levels were measured as indicated above.
Islet studies
Islets were isolated from 28-day-old (P28) or 8-week-old male mice by collagenase digestion. P28 islets were individually handpicked under a stereomicroscope after undergoing collagenase digestion, whereas adult islets were purified using a Histopaque gradient (Sigma-Aldrich) [18]. Insulin secretion was evaluated using freshly isolated islets in static incubation assays [19]. Insulin was measured by ELISA (Mercodia, Uppsala, Sweden).
Immunofluorescence and morphometric analysis
Pancreases from P28 and adult mice were dissected, fixed overnight in 10% formalin neutral buffered solution (Sigma-Aldrich) and embedded in paraffin. Sections (4 μm) were deparaffinised, rehydrated and treated with citrate buffer (10 mmol/l; pH 6.0) in a microwave oven. Primary antibodies used were: rabbit anti-RKIP (1:1,000; Calbiochem, Darmstadt, Germany), guinea pig anti-insulin (1:2,500; Dako, Glostrup, Denmark) and rat anti-cytokeratin 19 (DSHB, Iowa City, IA, USA). Cy2- and Cy3-labelled secondary antibodies (1:200; Jackson ImmunoResearch, Newmarket, UK) were used for immunofluorescence. Hoechst 33258 (Sigma-Aldrich) was used as nuclear marker. Images were taken with a Leica DMR HC epifluorescence microscope and a Leica TCS-SL confocal microscope (Leica Microsystems, Wetzlar, Germany).
For morphometric analysis, serial sections from three different levels for each pancreas block (six sections/animal) were stained with guinea pig anti-insulin antibody as used for immunofluorescence or with mouse anti-glucagon (1:1,000; Dako) using a modified avidin–biotin–peroxidase method and counter-stained with toluidine blue [20]. Slides were analysed using Image J (National Institutes of Health, Bethesda, MD, USA) software.
Proliferation and apoptosis measurements
For proliferation analysis, sections were stained with mouse anti-Ki67 (1:20; Dako, Denmark) as indicated above. A minimum of 3,000 insulin-positive cells per pancreas was counted in adult, P14 and P28 pancreases. For detection of apoptosis, the ApoAlert DNA fragmentation Assay Kit (Clontech, Mountain View, CA, USA) for tissue sections was used following manufacturer's instructions.
Western blot
Protein extracts from whole pancreas and islets were prepared in lysis buffer (50 mmol/l Tris pH7.5, 5 mmol/l EDTA, 150 mmol/l NaCl, 1% (vol./vol.) Triton X-100, 10 mmol/l sodium phosphate, 10 mmol/l sodium fluoride, 10 mmol/l sodium orthovanadate and protease inhibitors). Antibodies used for western blot were: RKIP (1:6,000), phosphorylated extracellular signal-regulated kinase 1 or 2 (ERK1/2) and total ERK1/2 (1:1,000; Cell Signaling, Beverly, MA, USA), GSK3 (1:1,000; Santa Cruz Biotechnology, Santa Cruz, CA, USA) and, as loading controls, actin (1:5,000; GE Healthcare, Hertfordshire, UK) or tubulin (1:1,000; Sigma-Aldrich).
RNA isolation and quantitative PCR analysis
Total RNA was prepared from whole pancreas using RNAgents Total RNA Isolation System (Promega, Madison, WI, USA) and from isolated islets using RNeasy Micro Kit (Qiagen, Venlo, the Netherlands). RNA was treated with DNase (Qiagen), and integrity was assessed using the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA). RNA was reverse transcribed using SuperScript VILO (Invitrogen, Carlsbad, CA, USA) following the manufacturer's instructions. Real-time PCR was carried out in a LightCycler 480 System (Roche) using SYBR Green (Mesa Green, Eurogentec, Seraing, Belgium). The primer sequences used are presented in electronic supplementary material Table 1. Expression levels were normalised to the expression of the gene encoding TATA box binding protein (Tbp) gene and expressed relative to the mean of the values of the same gene found in control wild-type (WT) animals, set at 1.
Microarray analysis
RNA from three WT and three Rkip1−/− pancreases was reverse transcribed, labelled and hybridised to mouse genome 430A 2.0 arrays (Affymetrix, Santa Clara, CA, USA) according to the manufacturer's protocol. Raw data was background-adjusted, normalised and summarised by robust multi-array analysis (RMA) using the Affy package [21]. Raw and processed data were submitted to several quality controls and analysed for statistical differences as described previously [5]. Briefly, analysis was performed with the LIMMA software package available from Bioconductor (www.bioconductor.org) [22], adjusting p values using Benjamini and Hochberg's method to control the false discovery rate at a value <5% [5]. Genes were clustered and represented in a heat diagram with dChip software (http://biosun1.harvard.edu/complab/dchip) [23]. Data have been deposited in NCBIs Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo/), accession number GSE31150.
Statistical analysis
Data are expressed as mean ± SEM and statistical significance determined by Student's t test. A p value <0.05 was considered statistically significant.
RKIP1 levels in the mouse pancreas
Glucose homeostasis in adult Rkip1−/− animals
Beta cell function and mass in Rkip1−/− animals
No differences in islet cell composition or beta cell volume were apparent between WT and Rkip1−/− mice (Fig. 4c,d). Yet, Rkip1−/− pancreases displayed significant alterations in islet size distribution, with more small islets and fewer medium and large islets in Rkip1−/− compared with WT animals (Fig. 4e). Islet density tended to be higher in Rkip1−/− mice than in controls (Fig. 4f), which could explain why, despite exhibiting a larger proportion of small islets, the relative beta cell area remained similar in Rkip1−/− mice to that in WT animals. The percentage of islets located near ducts (<5 μm) was significantly increased in Rkip1−/− animals (Fig. 4g).
Taken together, these data indicate that an augmented beta cell mass:body weight ratio, rather than alterations in beta cell functionality, is responsible for the improvement in whole body glucose control in Rkip1−/− mice [26]. Furthermore, while the relevance of altered islet size distribution and location in the control of glucose homeostasis remains unclear, our findings unravel additional potential effects of RKIP1 on islet morphogenesis.
Beta cell proliferation in Rkip1−/− animals
Our previous results suggested that RKIP1 might be involved in restricting beta cell expansion specifically around the lactation–weaning transition (P21–P28). To further support this possibility, we assessed whether changes in endogenous Rkip1 expression correlated with inhibition of beta cell proliferation during this transition in control mice. We observed a stepwise rise in the abundance of pancreatic Rkip1 mRNA, accompanied by a significant drop in beta cell proliferation rates between P14 and P28 (Fig. 5c,e). Remarkably, increased Rkip1 expression was not correlated with an increase in insulin (Ins1 and Ins2) gene expression (Fig. 5d). Thus, these findings support the notion that activation of Rkip1 expression could participate in restricting beta cell expansion at the end of lactation.
To elucidate the molecular basis for the enhanced beta cell proliferation in P28 Rkip1−/− animals we examined the phosphorylation status of the MAPKs ERK1/2, which are the canonical targets of the Raf-1/MAP kinase kinase (MEK) pathway. However, we found no significant changes in basal ERK1/2 phosphorylation in islets freshly isolated from Rkip1−/− mice relative to those from controls (Fig. 5f). RKIP1 also enhances GSK3β-dependent signalling through stabilisation of this kinase [9]. GSK3β is involved in β-catenin turnover and WNT/β-catenin signalling has been shown to regulate neonatal beta cell expansion [29]. Accordingly, GSK3β deficiency results in expanded beta cell mass [30]. These findings prompted us to examine whether the absence of RKIP1 affected GSK3β protein accumulation. However, we found no differences in GSK3β protein or Axin2 mRNA expression (an endogenous indicator of WNT/β-catenin signalling) between P28 Rkip1−/− and WT islets (ESM Fig. 2). Thus, although alterations in a small subset of beta cells or transient modulation of these pathways cannot be ruled out, these results indicate that neither MAPK nor GSK3β are constitutively changed in Rkip1−/− islets.
Pancreatic growth in Rkip1−/− animals
To elucidate the pathways responsible for increased pancreatic growth in Rkip1−/− mice, we performed whole genome expression profiling using pancreases from P28 Rkip1−/− and WT animals. Gene ontology analysis identified the cell cycle as the most significantly represented pathway among RKIP1-regulated genes (ESM Fig. 3). Among the genes most highly upregulated in P28 Rkip1−/− pancreases relative to controls, we identified those encoding the four members of the superfamily of C-type lectins known as regenerating islet-derived 3: Reg3a, Pap (also known as Reg3b), Ingap (also known as Reg3d) and Reg3g. Interestingly, Reg3 genes have been shown to function as stress response genes, antiapoptotic and growth factors in the digestive system and to specifically promote beta cell proliferation in the pancreas [31]. We confirmed these data by quantitative RT-PCR and found that Reg3 overexpression was only seen after weaning (ESM Fig. 3). However, Reg3 mRNAs were not overexpressed in isolated islets from P28 Rkip1−/− relative to WT animals (MPJ, RG unpublished observations), pointing to the exocrine pancreas as being responsible for Reg3 gene activation in Rkip1−/− animals.
Taken together, these data reveal RKIP1 as a negative regulator of postnatal pancreatic cell proliferation. Since cell cycle genes are mainly regulated at the post-transcriptional level, the molecular signature of Rkip1 ablation and its significance in pancreatic growth will need to be further explored through the identification of changes in cell cycle protein production in Rkip1−/− pancreases.
Rkip1 deletion ameliorates STZ-induced diabetes
How beta cell mass is regulated is a critical issue for understanding the pathophysiology of diabetes, which is characterised by a complete (type 1) or relative (type 2) deficiency in beta cell number. During mouse embryogenesis, new beta cells arise through the proliferation and differentiation of a population of progenitor cells. During postnatal development, between birth and weaning, there's an additional and massive increase in beta cell mass that mainly involves replication from pre-existing beta cells, even though neogenesis is maintained at least during the first week of life. By the time of weaning, beta cell proliferation decreases and is maintained relatively low throughout adulthood (for reviews, see [26, 32]). In this study we aimed to investigate the physiological role of RKIP1 in the regulation of beta cell mass. Our results indicate that RKIP1 participates in the control of pancreatic growth, particularly at the time of weaning. In addition, we demonstrate that the absence of RKIP1 confers significant protection against STZ-induced diabetes, thus indicating that this protein may negatively influence beta cell regeneration after injury in the adult pancreas.
Rkip1−/− animals exhibit increased beta cell mass relative to body weight and this augmentation, in the absence of changes in insulin sensitivity, is the likely cause for their improved glucose tolerance. Indeed, beta cell mass expansion and body weight follow a linear correlation throughout life [28], and alterations in this correlation are known to affect glucose homeostasis [26]. A recent study showed that beta cell-specific deletion of Raf-1 kinase results in the downregulation of Ins2 gene transcription and, consequently, in blunted insulin secretion [25]. In contrast, we have found that the insulin content, insulin gene expression and glucose-induced insulin secretion of Rkip1−/− islets is similar to that of WT islets (Fig. 3 and data not shown), arguing against a major involvement of altered islet function in enhanced whole body glucose control in Rkip1−/− mutant mice. Yet, it is conceivable that, in adult islets under normal physiological conditions, Raf-1 kinase is already maximally stimulated, so that elimination of RKIP1 has no measurable effects on Raf-1 kinase-dependent processes.
In accordance with prior in vitro experiments [13], we have observed that RKIP1 inhibits beta cell proliferation in vivo. Remarkably, the inhibitory effect of RKIP1 is only evident during early postnatal stages when the beta cell proliferative capacity is maximal. This age-dependent loss of the effects of RKIP1 may simply reflect changes in the repertoire of signalling factors available to the beta cell at any given moment in time. Alternatively, changes in the responsiveness of beta cells to specific signalling molecules, rather than their availability, may underlie the age-dependent effects of Rkip1 ablation. In line with this, Chen et al [33] have recently linked age-triggered loss of beta cell expression of the platelet-derived growth factor (PDGF) receptor to reduced beta cell proliferation. Hence, it is tempting to speculate that the proliferative response to Rkip1 ablation will be lost in parallel with the loss of the ability of the beta cell to respond to specific factors.
Genetic mouse models and in vitro studies have helped unravel the identity of growth factors that stimulate beta cell replication, but their role under normal physiological conditions remains uncertain. Among the pathways implicated, many transduce signals through the Raf-1/MEK/ERK cascade, including insulin, insulin-growth factor, hepatic growth factor, epidermal growth factor and PDGF [34, 35, 36], and thus could potentially be targeted by RKIP1. Yet, our data indicate that constitutive ERK1/2 activation may not be linked to enhanced beta cell proliferation in Rkip1 mutants. In a similar way, deletion of Raf-1 does not result in decreased ERK1/2 phosphorylation in pancreatic islets, indicating that other Raf-1-dependent pathways may be operative in beta cells [25]. Additionally, RKIP1 may function through Raf-1 independent mechanisms involving NF-κB [8], GSK3β [9] or G protein-coupled receptors [11]. Apoptotic rates are comparable between Rkip1−/− and WT P28 pancreases, implying that NF-κB-dependent survival pathways are not affected by Rkip1 deletion. On the other hand, RKIP1 deficiency does not alter levels of GSK3β in islets, as reported in other tissues [9], ruling out this possible mechanism. Future work should be aimed at delineating the signal cascades regulated by RKIP1 and their connection to beta cell mitogens during physiological beta cell growth.
This study reveals that RKIP1 is not only involved in restricting beta cell proliferation but it may also inhibit postnatal pancreatic growth. Gene expression profiling has identified the Reg3 gene family as potentially involved in the stimulatory effect of RKIP1 ablation on pancreatic growth at P28. Interestingly, the Reg3 genes have been previously associated to pancreatic regeneration and islet cell neogenesis [37, 38, 39, 40, 41]. Further supporting a role for Reg3 genes in pancreatic postnatal development, a recent study has described the upregulation of Reg3 genes in the mouse pancreas between P7 and P30 followed by their subsequent downregulation in adulthood [42]. In this scenario, our data suggest that RKIP1 may participate in restricting Reg3 gene expression after weaning and, in this way, control pancreatic growth. The question of whether exocrine Reg3 gene activation might contribute to enhanced beta cell proliferation in Rkip1−/− mice remains unresolved. Double Reg3 and Rkip1 mutants and beta cell-specific Rkip1−/− mice will be necessary to properly address this issue.
In summary, in this paper we show that RKIP1 inactivation results in enhanced beta cell and pancreatic growth in postnatal stages, leading to an increment in beta cell mass and improved glucose tolerance in adult animals. Furthermore, Rkip1 deletion confers recovery to STZ-induced hyperglycaemia in adult animals. These results have therapeutic implications for the development of novel strategies to trigger beta cell mass expansion in diabetes.
The authors thank A. Eriksson (Umeå University) for the optical projection tomography analyses.
This work has been supported by grants from: Spanish Ministerio de Ciencia e Innovación (SAF2010-19527 to R. Gomis and BFU2008-02299/BMC to R. Gasa), Generalitat de Catalunya (2009 SGR 1426 to R. Gomis), Fondecyt no. 1090694 (Chile) and Fundación Marcelino Botin (project 08/351) and the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PIAP-GA-2008-218130 (to R. Gomis). Predoctoral fellowships were provided by Fundación Marcelino Botin (F. N. Pardo), Conicyt-PhD (F. N. Pardo), IDIBAPS (J. Altirriba) and Spanish Ministerio de Economía y Competitividad (M. Pradas-Juni).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
Contribution statement
FNP designed, performed the study, analysed and interpreted data and drafted the manuscript. JA, MPJ, AG and UA made substantial contributions to the acquisition, analysis and interpretation of data and critically revised the manuscript. AB, JCS and AJY contributed to data analysis and interpretation and critically revised the manuscript. RGo and RGa designed the study, supervised the project, interpreted data and wrote the manuscript. All authors have approved the final version of the manuscript.


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Round-Up: Two more flu deaths; EPC passes MJ ban; New Belgium now 100% employee-owned
By Andrea Chalfin News Dir. On January 15, 2013 · Leave a Comment · In Andrea Chalfin, AP, Beer, Business, Children & Youth, El Paso County, Grace Hood, Health, KRCC News, RMCR, Round-Up
Two children have died from flu in Colorado, one in El Paso County. That brings the total this season to four pediatric deaths. As of January 12th, the Colorado Department of Public Health and Environment says more than 650 people across 36 counties have been hospitalized due to the flu.
El Paso County Commissioners gave final approval to an ordinance that bans recreational marijuana businesses in unincorporated areas of the county. The measure passed 4-1 with Commissioner Peggy Littleton opposing. According to a release from the county, Littleton encouraged the commissioners to wait until after the state makes decisions on marijuana regulation before finalizing county rules. The new rules do not affect medical marijuana businesses.
Fort Collins-based New Belgium Brewing is now completely employee owned. The nation's third largest craft brewer made the change earlier this week, which impacts more than 450 employees. CEO and co-founder Kim Jordan says the company had been partly owned by its workers since 2000. This week's announcement takes the company to the next level…
"One of the really great parts about this is that it's the next chapter for us in how you prove this concept of high involvement culture, open book management, employee ownership creativity making our own path and rules."
Jordan says she will remain CEO, and the company's management team will remain in place. She adds employee ownership could be a strategy other craft brewers consider as they navigate through an increasingly consolidated industry.
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what coordinate point is the solution to the system? {3x+2y=8 {x-y=1 (2,1) please don't think i just made that up, it's correct. you have to use substitution, when you do solve for x and y, you get: x= y+1 and y=x-1, plug in y for 3x+2y=8 and you get: y=1, then plug in "1" ...
7th Grade Math Help
Hi, I really need some help with this. What is one example of how prime factorization is used in real life? I really don't know and I know what example you can use for factoring in real life but not this one. Please help as fast as possible! I really appreciate it! :)
I really really need help with this, PLEASE. I need to list the nouns, verbs, and adjectives that establish and shape the mood of the poeom El Olvido by Judith Ortiz Cofer. Please, just give me some examples Thanks -MC
i really need help im really confused on what to do to find the percentage write 3 3/5 as a percentage
Modernist Poetry
I want to write a modernist poem about struggles, future, stress. How everything I do in grade 12 will affect my future. The amount of pressure that is put onto me by my parents to get into university. I need a lot of help. I've always struggled with poems. I really need help...
Math repost for Jordan
i have some math questions that i really ,really,need help with asap if any body can explain some of these questions that will be great help.Ok here are 3 of the questions i am about to type now ok the first one says,whole 16 nickels a.circle 3/a of the nickels b.how much ...
help whit math
I need a website to study off of I have a times and fractions test help. I really need help if I don't turn it in I get an f help.
Math ---Helper
Helper I really need ur help with some of my math questions down below, ur the best math tutor on here, need ur help please.
check please
hi ms. sue i was wondering if you had email that i can have to email you if i need help because i need help with accounting with some type of graph but it wont fit here is there anyway you could help me through your email or i can send it to your email and you help me out ...
I am doing a presentation on the efficiency of appliances. I am going to be comparing the past and the present and then France and the US. Do you guys know of any good websites that would talk about any of this. All I can really find is different brands of appliances and then ...
I am doing a presentation on the efficiency of appliances. I am going to be comparing the past and the present and then France and the US. Do you guys know of any good websites that would talk about any of this. All I can really find is different brands of appliances and then ...
A 4x4 grid with 5 blocks shaded in, I need to write a percent and a ratio for it. A. 1/5, 25% B. 5/16, 31.2% C. 1/4 , 20% D. 1/4, 25% C? Im not really sure on this one, I just need some help.
English III
Okay so I am reading the book The Scarlet Letter and it is like really boring, so far. I am about a chapter in and my homework is really hard! I have to read a sentence the packet gives me and interpret the darn thing. It's driving me insane because these things are really ...
Identify commonly used lab equipment. (beaker, graduated cylinder, triple beam balance, test tube, Patri dish) I really don't need answer. Does this means I have to write definitions for each lab equipment???? I really need help.
PreCalculus REINY HELP PLEASE
well yay thanks for the answer but i really need the formula lol I tried to derive it on my own but it was a little bit rough lol i need the formula it wasn't in my book and I don't know what the name of the formula would be so i can't really google it...
Science Fair Project
Please help any tutors around, i really need help on what topic to choose, and my science fair is in February 16, 2015!!!!!! I just want to get a really good mark so i get an A in Science again this year in my report card. From a Student in need!!!Wimbika
algebra 2
A. I need to write an equation to the linear equation..(-2,-2), (3,3). B. I need to graph the function of y=|x| on a coordinate plane. C. I need to give one similarity and one differnce for the equations and graphs in parts A and B. I really need your help on this i don't ...
PLEASE HELP! Math
I really need help with this one question on my math pretests and I have no idea what to do! The question is: Mandy begins bicycling west at 30 miles per hour at 11:00 am. If Liz leaves from the same point 20 minutes later bicycling west at 36 miles per hour, when will she ...
Algebra-I really need help, please?
I have to solve sqrt(2x-7) >=5 answers would be x>=16 x>=7/2 7/2<=x<=16 x<=16 I don't get this concept at all and I have 20 of these kinds of problems for homeowrk-can someone direct me how to start or give me an example or just help please? I really need to ...
Hi ! Can someone give me some really really really good websites about the "Manhattan Project" (WWI/WWII).. you know.. I need ONE primary resource and ONE secondary resource. I know you guys are really good at giving good websites. I cannot use wiki, or anything bogous and ...
Math - help really needed
I'm sorry to double post; I don't want to seem impatient, but I really need help with this. Prove each idenity. 1+1/tan^2x=1/sin^2x 1/cosx-cosx=sinxtanx 1/sin^2x+1/cos^2x=1/sin^2xcos^2x 1/1-cos^2x+/1+cosx=2/sin^2x and (1-cos^2x)(1+1/tan^2x)= 1 I haven't even gotten 'round to ...
I really, really need help! Solve for the indicated variable. 8x+4y=12 Solve for y. Explanation too, please! Please and thanks!
5th grade math
can you please explain &show me how to get these answers to common denominators,find the sum & difference,write in simplest form,7/10-3/5 =,2/3-1/6 =,5/6-7/12 =,5/12+1/4=,1/6+2/9=,5/8+1/2=,3/8+1/4= i'm really having a huge problem understanding this,it's getting late,i'm ...
I need to change this expression to postfix form. (12*A^2-2*A+31)/(4*A+6) I know how to do this except for the squaring part. I got stuck. This is my try. 12 A 2 ^ * 2 A * - 31 + 4 A * 6 + / When I test this in a calculator, it gives different results. Another problem is that ...
7th Grade Science
Hi, I really need help with this. I'm asked to write a paragraph about this. I just need some help working it out so I can get everything correct. I'm not cheating its just confusing this part of the assignment for me. So please help! I also have to study for Math State Test ...
Math help please
Sorreh I never really post question but I need help with this Write a real world problem that you can model with the two step equation 5x+7=10. Then solve the problem. I would really like it if Some one could explain this to me!! thanks agian ~lost gurls finding home in neverland
6th Grade Science
Hi, I really need help and I'm really confused I don't know what they are asking me to do. Provide three statements that demonstrate the importance of units when describing motion. Please someone help me because it is very important. Thank You :/
really need help!!! solve 25-y=7, 5 - y/3 y= -3 y/3 = -9, 3y + 8 = 3 and 5 - 3y =7
really need help in math
24x^2y^2 ?
i need help thinking of Criterion for my evaluative essay..i'm writing on a piece of literature..i need to write what criteria i'm going to use to evaluate the work.. i really need help with this..i need to come up with atleast 4 criterions and i'm stuck please give me some ...
English (I really need help!)
I need one more haiku for my assignment(I have already created 4, I need 5) My brain has run out of ideas! It should be about "A Lost Love"
Leiningen Versus the Ants" by Carl Stephenson.ASAP
Okay, so I really need help, I have read the story, but I realy need help. Has anyone read "Leiningen Versus the Ants" by Carl Stephenson. Before. I really need help so please help.
Math--need help fast
If the radius of a circle is x/6, what's the diameter and circumference? Diameter = 2*r Circumference = 2*pi*r ...or... Circumference = pi*d Note: I'm using * to mean multiply. Can you now determine what you need to know with this information? Not really. I just need to know ...
How do you do metric conversions? i really need help
Math! I really need help!
20y=17.5x How can I find x and y
Square root 2x-4 + 5=7 I really need help with this. Thanks
Mathmate, I really appreciate all your help regarding my composite function question below but I'm still in need of your help. I don't understand how the range of x^2-x+1 is R. Isn't this a parabola with a minimum for y? Also, I understand minimum and maximum values of sine ...
Can someone please explain to me how to graph sine and cosine step by step because I am so confused and I really really need help.
Can someone please explain to me how to graph sine and cosine step by step because I am so confused and I really really need help.
Please help find the rational roots of f(x)=4x^4 - 3x^3 + 2x^2 +x - 3 another is f(x)=-3x^3 - 2x^2 + x - 1 I tried but still confuse please help really really need help Thank you very much!
I really need to get a WORKING charger for my phone. Participle or verb? I think it's a verb, but I'm really not sure.
I really stuck on binomial theorem and I have a whole worksheet due Monday How do I solve (x+5y)^4 I need to really understand this-please explain the steps so I can learn from it and then use it to do the other problems
Help on social studies!
Hi! I was wondering if anyone could give me any websites to research on how forest, a resource, is collected and gathered. I try to look at some things, but nothing really captures what I need to type. Thank you! :) And, I really appreciate it!
i really need help! 6z=4(1/2z-8) I really don't know what to do
Hi, I really need help on two questions for the novel called 'In the heat of the night! Here's the questions btw its chapter three In the chapter 1 and 2, the racial issue has been hinted. Now we sees clear indication that this issue will be a major item in the story. ...
Art help me please i need it soon
haystacks in brittany by paul gauguin the artis most obviously showed experimentation through his use of perspective texture *** color line Achille de gas in the uniform of a cadet how was portion used in this image to create a mood of tranquility to create an optical illusion...
I need help with this equation, I am really bad at fractions. m^2 - (49/2 * m)= 1/2
I need help with this equation, I am really bad at fractions. m^2 - (49/2 * m)= 1/2
I really need help with these questions I am very confused !!! 16^-1(2^5) 3^-26^-2+3/2(-9)^-1 (5^0+5^2)^-1
Math; I really need help.
Write this in standard form. y=-5x
4/5 • m = 7 m=? simplest form. please I really need help!
math really need help!
let f(x)=-5x+6 find and simplify f(x+2) f(x+2)=___
1/5(2x-10) + 4x = -3(1/5x + 4. Solve for x. I need some really help! please and thank you
i really need help with this question solve the inequality x>7 a.9 b.5 c.1 d.7
i really need help with this question solve the inequality x>7 a.9 b.5 c.1 d.7
Again, I'm learning about trigonometric functions. I need to find the missing information for each triangle. I have the length of one leg as 24 and the opposite theta as 72. I need to figure out the other angles and side lengths, but I'm really not sure how to.
i really need help in math. im just in 6 grader and i don't understand this' 24x - 10 = 18x - 4
reading...please help
i need to know who the antagonist is in the story money hungry and i need to know what the conflict in the ook is please help me....i really need help i gotta know this by tomorrow!
math REALLY NEED SOME HELP
question 10 on unit math review find the are....its hard!
Kerry skates laps around the playgroung. The playground is 150 meters long and 50 meters wide. How many laps will it take her to skate 1 kilometer? I need els really badly and I av a math test tommorow I need to study perimeter and area.... I old appreciate ur help. Tnx😊
i really need some help!! i understand the parts of the heart and their names, but i am really confused on the cardiac cycle graph that shows the pressure of the heart at certains stages HELP ME PLEASE!
Without this system in the body, you would get really sick because toxins and waste would build up? (A) Cardiovascular (B) Excretory (C) Integumentary (D) Muscular I think its A, I really need this answered.
well this is not really a question i am not really good at spanish and i need help with writing an esay
I really need help with this problem!!! Solve for the unknown: 8/52=m/39 Help Please!!!!
What is an interpet in mathmatical terms? i really need help with my homeework!
Math Fractions
12/12 divided by 3/8 i really need help someone plz help!!!!
Math Fractions
12/12 divided by 3/8 i really need help someone plz help!!!!
Math Fractions
12/12 divided by 3/8 i really need help someone plz help!!!!
Math Fractions
12/12 divided by 3/8 i really need help someone plz help!!!!
Math Fractions
12/12 divided by 3/8 i really need help someone plz help!!!!
if i cross multiply 1/2*4/22 what will i get.... just really need an example
Math Help
Hi! I really need help with this. I'm so confused. Thanks! :) If h(x)=4/(5x+2)^2, find the two functions f and g so that f(g(x))=h(x).
Q. 460 divided by 30 A. I don't really get division,so I need help please.
math i really need help!!
What is (5.93x10^5)-(2.71x10^4) scientific notation..
1/5(2x-10) + 4x = -3(1/5x + 4. Solve for x. I need some really help! please and thank you. Ms.Sue?
I need help with magnitude estimates. They are really hard for me . Please help!
I really need help with this please help me. 360 kilometers is 24% of ______kilometers


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Pitted Against Each Other, NJ Incumbent Dems Battle for Party's Progressives
Democrat incumbent New Jersey Congressmen Bill Pascrell and Steve Rothman used their final broadcast debate Monday night to try make a pitch for the party's progressives ahead of the June 5 primary to decide who should represent the freshly drawn 9th district.
The two incumbents, with relatively similar voting records, are vying for the same seat because New Jersey lost a congressional district through redistricting.
During the heated debate at Montclair State University Monday, Rothman said his opponent was late to support same-sex marriage, voted for tax breaks for the wealthy and had an inconsistent voting record on reproductive rights.
"I'd say I am the progressive voice of the Democratic Party represented here. I am the Democrat's Democrat up here," Rothman said.
Pascrell accused Rothman of "deceitfully" distorting his voting record that Pascrell said included votes cast to help win compromises that set the stage for the passage of President Obama's Affordable Health Care Act.
Pascrell made his own pitch for left-of-center Democratic voters while also making a play for the veterans' vote.
"I have recommended and suggested and support cuts in the defense and I am a military guy. I am the veteran on this stage," Pascrell said.
Both candidates did their best to tie themselves to the current Democratic administration in the White House. Pascrell pointed to his endorsement by Bill Clinton, and Rothman reminded the audience of his early support for President Barack Obama.
Analysts say that without a presidential contest, the June 5 primary is likely to draw just one in five Democratic voters. That means both campaigns have to be extra attentive to key constituencies that are known to turn-out.
The 9th District is home to one of the largest concentrations of Arab-American voters in the nation.
In a pitch for those voters, Rothman reminded the audience of his response to the disclosure the NYPD had conducted covert surveillance in Muslims and their businesses in Newark.
"When the New York Police Department was charged with surveilling Muslim Americans in New Jersey, I was the only one of the two of us up here that wrote to Attorney General Holder demanding an investigation," Rothman said.
Pascrell expressed his support for Imam Mohammad Qatanani of the Islamic Center of Passaic County who faces deportation over allegations he concealed his support of Hamas. Qatanani denies the affiliation, and has been lauded for his post-9/11 work with law enforcement.
The new 9th includes eastern and southern Bergen and portions of Passaic and Hudson counties.
The two men will debate a third and final time on May 23 at the Ethical Culture Society in Teaneck. The debate will not be broadcast.


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Cops want to get paid, too.
From 1982 to True Detective.
And why we may soon not be able to measure it at all.
And why they're not likely to get everything they want.
You can do a lot of things while high, but driving shouldn't be one of them.
Learn it, live it.
How do you legalize drugs in the nation's capital?
A GIF to remember the endless snow of 2014.
In states with newly relaxed marijuana laws, it's difficult to see teen use not going up at least a little bit.
And what Florida is planning to do about it.
You've heard of stop-and-frisk. Now meet stop-and-identify.
A subtle, but crucial policy tweak recognizes the importance of officer behavior pre-shooting.
A lesson in bad government contracting.
Roughly 60 percent of Mexico's federal prison population is serving time for drug crimes.
A harbinger of things to come?
What if extra lights don't make us as safe as they make us feel?
Liquor stores and other independent retailers are set to profit off of the chain's move.
Russia has 40,000 police and military staff on the ground for the Olympics. Will it be enough?


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Reset My Password
This will send a password reset to your email address on file. A reminder that your email address on your account must be valid and working to receive the reset request.
We would love to hear your feedback and any suggestions you may have for our new VWVortex store.
Let us know if there is a color option you would like added or a particular merchandise item you would like to see in the store. Have you had a chance to buy an item from our store? Then we want to hear what you think about the merchandise you bought.
If you would like to provide feedback/suggestions please post in here in the Store Feedback forum.
Just an FYI to our most ardent readers and Audi fans, Audi will he holding an exclusive invitation only event this weekend at the Audi Forum New York at Park and 47th in Manhattan. We've got a number of invitations blocked for Fourtitude with the intention to share with our readers.
What's the event? We have it on good word that this will mark a premier of the new 'Truth
Thus far this week, we've posted galleries from three recent visits to the Audi Forum Ingolstadt on October 18 , October 20 and October 21 . Hitting the same place in just such a short amount of time, we'd expected to begin to see the same old same old... and were quite surprised when we were wrong. Our fourth and final visit (for now), came about a week later
As mentioned, over the last two weeks we've had the rare chance to visit the Audi Forum Ingolstadt on four separate occasions. What we found was that there's nearly always something very, very unique in the Audi lexicon to see in and around the brick piazza that makes up the heart of the forum at Audi's headquarters. Of course intended destinations like the Museum
Over several years of Super Bowl advertising Audi has taken various levels of interest in the on-site aspect of its promotion. This year, with the all-new A8 in the mix, Audi went big by creating the temporary but no less impressive Audi Forum Dallas in which to entertain its guests.
As things tend to go, celebrity sightings are a big part of the process and this year was not short on this particular
Check out these images of an S5 Cabriolet we've found over at Audiblog.nl. The car appears to be a stock Ibis White S5 Cabriolet with 20-inch wheel option other than what appears to be an OEM front fascia from the RS 5.
There's no actual confirmation that the piece is the RS 5 piece or something new from Audi but we're guessing it is the stock RS piece. Knowing though is interesting because


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Roger Williams University is a leading independent, coeducational university with programs in the liberal arts and the professions, where students become community- and globally-minded citizens through project-based, experiential learning. The University's fundraising priorities are focused on a dedication to the success of students through a commitment to a set of core values, the pursuit of Affordable Excellence and by providing an educational experience that is relevant, accessible and affordable.
One of the hallmarks of an RWU education is the opportunity for students - at both the undergraduate and graduate levels - to engage in meaningful, project-based educational experiences which address real community needs through coursework, team projects, scholarships, internships and externships. The Roger Williams University Community Partnerships Center (CPC) is a centralized home to an array of RWU resources from within RWU's liberal arts and professional degree programs, as well as from strong relationships with external organizations. Through the CPC, these resources are organized and made available to a wide spectrum of non-profit, municipal and community groups to carry out projects throughout Rhode Island and Southeastern Massachusetts.
By supporting RWU with your philanthropic donations, you are helping to preserve and improve an institution that is helping generations of young men and women on their own paths of professional and personal growth. In addition to Affordable Excellence and the CPC, the University has identified key priority areas requiring on-going support, including; capital projects, scholarships, faculty support and research. In addition, the University offers opportunities to support special campaigns and program initiatives.
The Office of Institutional Advancement
(401) 254-5383


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"Though I speak with the tongues of men and of angels, and have not charity, I am become as sounding brass, or a tinkling cymbal. And though I have the gift of prophecy, and understand all mysteries, and all knowledge; and though I have all faith, so that I could remove mountains, and have not charity, I am nothing."
- 1 Corinthians 13:1-2
Anyone visiting or driving by St. Charles Catholic Church may notice a bright, white statue depicting the crucifixion of Jesus. The statue was first built in 1946 in memory of a former student at St. Mary's College, and it was recently restored.
"It is my hope that future generations of the community will visit it as a reminder of what it represents," said John Browning, a member of the St. Charles cemetery committee.
Seven monks from the Labrang Tashi Kyil Monastery in Dehra Dun, India, will be visiting Marion County through Sunday. These monks are part of the same tradition as the Dalai Lama.
• Every day through Friday, Oct. 11: Mandala sand painting at the Marion County Public Library, starts at 9 a.m. Come once or make multiple visits to see the monks' progress. For more information, call 270-692-4698.
Calvary's Way Church will be presenting "In His Presence Ministry" at 6:30 p.m. Monday, Oct. 7 at Hampton Inn. Revivalists will be Glenn and Jessica Meldrum from Phoenix, Arizona. Pastors are Steve and Sandra Rawlings. For more information call 270-692-0789.
By Dr. David B. Whitlock
Friends and Family Day
First Baptist Church on N. Depot St. will be having a Friends and Family Day at 11 a.m. Sunday, Sept. 29.
Bible Day Camp
Gravel Switch United Methodist Church will be hosting a Bible Day Camp from 2 to 6 p.m., Saturday, Sept. 21. The event will include music, lessons, crafts, games, and at 5:30 p.m. there will be a community cookout and live music with a campfire and story telling.
Prayer Day
Copyright © 2017
The Lebanon Enterprise is your source for local news, sports, events, and information in Marion County and Lebanon, KY, and the surrounding area.


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Patient Privacy
Alliance Citizens Health Association
Alliance Community Hospital
Alliance Hospice
Alliance Visiting Nurses Association
Caring Hands, Inc.
Alliance Medical Associates
Health Alliance
Community Care Center
ACH Family Care - Urgent Care Center
Alliance Community Medical Foundation
After Hours Care
Alliance Community Hospital and its affiliated health provider entities listed above ("we" or "our") are committed to safeguarding the privacy and security of your Protected Health Information ("PHI") in paper and electronic (computer) form. We have adopted practices that comply with HIPAA's Privacy Rule (as amended) to protect the use and disclosure of your PHI. It is posted on our website: www.achosp.org. If you do not have a computer or internet access, or if you want a paper copy of this notice, you may request a paper copy at any time by calling (330) 596.6000.
Please read this notice and share it with your family or personal representative. Not every use or disclosure of PHI, with or without a signed authorization, may be listed. Uses or disclosures not specified in this notice generally will require an authorization. If you have questions, please call our Privacy Officer at 330.596.7161.
Use and Disclosure of PHI for Treatment, Health Care Operations, and Payment (TOP)
We will create, receive, or access your PHI, which we may use or disclose to other covered entities for treatment, Health Care Operations, and Payment ("TOP") without your need to sign an authorization.
Covered Entities
Covered entities include health care providers (e.g. hospitals, doctors, nurses, nursing homes, home health agencies, durable medical equipment suppliers, and other health care professionals and suppliers) and group health and plans.
Use means our accessing, sharing, employing, applying, utilizing, examining, or analyzing your PHI within the hospital and its affiliated health provider entities.
Disclose or Disclosure
Disclose means our releasing, transferring, providing access to, or divulging in any other manner your PHI to a third party outside of the hospital and its affiliated health provider entities.
Treatment means the provision, coordination, or management of health care and related services by one or more health care providers, including referrals and consultations between providers. We will use your PHI for your treatment, which includes (but is not limited to) radiology, laboratory and other diagnostic tests, medical treatment, surgery and other procedures. We will disclose your PHI to other hospitals, doctors, pharmacies, health care professionals, and facilities that are involved in your treatment or to whom you are being referred as part of continuity of care. We will not disclose your PHI to persons who are not involved in your treatment, unless they are participating in health care operations, without your authorization. We have physical, technical, and administrative safeguards in place to protect against unauthorized access.
Health Care Operations
We will use PHI for health care operations, which include (but are not limited to) quality assurance, performance improvement, peer review, risk management, and compliance. Health care operations also include preventive, wellness, case management and related services.
We will use and disclose PHI when checking with your health plan or third-party payer about eligibility, coverage, pre-certification, or when billing and submitting claims for payment of treatment we provided. You may ask us not to submit a claim containing certain PHI to your health plan or third-party payer. We will honor your request if you pay your claim out-of-pocket in full.
HIPAA permits us to disclose information to collection agencies if you do not pay your bill. If you are injured in an accident, or if another party is responsible for paying for your medical care, we may be legally obligated to send our bill for treatment first to the responsible party's commercial payer or to the responsible party if the commercial payer is not known. This also applies (without limitation) to our obligation under Medicare's Secondary Payer Rules.
Business Associates
We may contract with outside persons or entities called business associates who access PHI to perform covered functions for us. Business associates, including their agents and subcontractors, must protect the privacy and security of your PHI to the same extent we do.
Minimum Necessary
Except when PHI is used or disclosed for treatment, we will limit the use or disclosure of your PHI to the minimum necessary to accomplish the intended purpose of the use, disclosure, or request of PHI.
Communicating with You, Your Family, Personal Representative, and Persons Involved in Your Care
Communicating with You
We may contact you for scheduling or reminding you of appointments, giving you test results, or refill reminders. We may contact you by mail or telephone. If we call you, we will identify ourselves and ask to speak with you. If you are not available, we may leave a message for you to call us, but we will not disclose details about your medical condition or PHI in that message.
Services and Programs
We or a business associate may contact you about health care services, prescription refills, treatment alternatives or health-related benefits, services, case management, wellness and preventive care programs, such as smoking cessation, weight management, and education programs. We or a business associate also may contact you in follow-up to services regarding your satisfaction. We will not sell your PHI to third-parties for marketing. Any use or disclosure of your PHI for marketing will require your signed authorization. If you do not want to be contacted or receive information about these services and programs, you may opt out by contacting (330) 596.6000. Opting out will not affect any care, treatment, or services we provide to you.
We may contact you about fundraising. If you do not want to be contacted or receive fundraising materials, you may opt out by contacting (330) 596.6000. Opting out will not affect any care, treatment, or services we provide to you.
You May Request that we Contact You by Alternate Means
You may request us to contact you by alternate means or at a different telephone number, address, or email address from what you usually use. Let us know if you do not want us to send information to you at your home address, a particular email address, call you at home, or leave a message. You do not have to explain the reason for your request.
Family and Friends
We will include you in our patient directory, which may list your name, room number, general condition and religion. Directory information is available to family, friends, clergy and others who ask about you by name. You may request that we do not list you in the directory, or you may restrict access to certain persons whom you identify by notifying Patient Registration. If you are not listed in the directory, we will not disclose or confirm any information about you, including whether you are a patient.
Most patients allow us to discuss their PHI with family members, guardians, persons named in a health care power of attorney or advanced directive (living will), personal representatives, or others who are assisting in your care or helping you with your medical bills. This may include discussing or answering questions a family member (spouse, adult children, parents, guardians, or personal representatives) may have about your condition, treatment, medication and refills, or appointments. It also may include answering questions about your medical bill. We will assume that you will permit us to talk with family members and those assisting you, unless you direct us not to. We will communicate with family members or others involved in your care in emergencies, or if required by law.
Emancipated and Mature Minors
We usually will share the PHI of a minor (a person less than 18 years old) with the minor's parent(s) or guardian. We will not share PHI with the parent(s) or guardian of an emancipated minor. A minor is considered emancipated if he or she: (1) does not live with his or her parent(s); (2) is not covered by parental health insurance; (3) is financially independent of parent(s); (4) is married; (5) has children; or (6) is in the military.
In some cases, if requested, we may not share PHI of a mature minor (over 14 but less than 18) with the minor's parent(s), guardian, or health plan for certain conditions, including alcohol or substance abuse, obstetrical care, or STDs. We will encourage the minor to involve parent(s) or guardian.
Deceased Patients
We will disclose PHI of deceased patients to the probate court's appointed executor or administrator of the deceased patient's estate. We also may disclose PHI to the patient's spouse, family, personal representative, or others involved in the patient's care or management of the patient's affairs, unless doing so is inconsistent with the patient's expressed wishes known to us. We may disclose PHI of any deceased patient without an authorization after 50 years.
Use and Disclosure of PHI You Authorize and Your Right to Cancel Authorization
We will not use or disclose your PHI other than for treatment, health care operations, or payment ("TOP") without your signed authorization, except as stated in this notice or otherwise required by law. we will not condition your treatment on your signing an authorization.
The date on your authorization generally should not be more than 30 days before your give it to us. we may ask you to sign a new authorization if the date is more than 60 days, or we have other questions. This is for your protection. You may fax a copy of your authorization to us at (330) 821.6471.
We will not disclose psychotherapy notes without a signed authorization unless required by law.
We will not disclose your PHI to your employer without your authorization. We will not release medical records if we are subpoenaed, unless you sign an authorization, or the lawyers sign a qualified protective order, or if we receive a court or administrative order.
You may authorize us to disclose PHI to persons who are not covered entities or business associates under HIPAA. Once that information is disclosed to a non-covered person, HIPAA no longer applies. A person or entity not covered by HIPAA may use or re-disclose medical information it receives in any way that is not prohibited by law.
You may cancel your authorization in writing at any time by notifying us in person or faxing us the written cancellation at (330) 821.6471. Once we receive your written cancellation, we no longer will disclose your PHI. We are not responsible for any use or disclosure of PHI according to the Authorization before we receive your written cancellation.
Use and Disclosure of Health Information Permitted or Required by Law
We may use or disclose PHI, without an Authorization, as permitted or Required by Law, including the following:
Workers' Compensation. Ohio law permits us to disclose health information, without a separate Authorization, when an employee files a Workers' Compensation Claim or seeks benefits for work-related injuries or illnesses.
Public Health Agencies. Ohio law requires us to disclose PHI to public health agencies for reporting births and deaths, to help control disease, injury or disability. The law requires us to report cases of suspected abuse, neglect, or domestic violence.
FDA and OSHA. Certain Federal laws from the FDA and OSHA require us to disclose PHI in reporting adverse events, product problems, and biological product deviations, so safety precautions, recalls and notifications can be conducted.
Regulatory Agencies. We will disclose PHI to certain Ohio and Federal governmental regulatory and health oversight agencies for purposes of their reviewing health care system, civil rights, privacy laws, and compliance with other governmental programs.
National and Homeland Security. We may disclose information concerning patients to authorized federal officials for intelligence and other national and homeland security purposes.
Protective Services for the President and Others. We may disclose medical information about you to authorized federal officials, so they may provide protection to the President, other authorized persons, or foreign heads of state and officials, or to conduct special investigations.
Red Cross and Armed Forces. We may disclose PHI to the Red Cross or armed forces to assist it in notifying the patient's family member of the patient's location, general condition, or death.
Coroners, Medical Examiners, and Funeral Directors. We may disclose PHI to coroners, medical examiners, or funeral directors for them to perform legally authorized responsibilities.
Law Enforcement. We may disclose PHI to law enforcement officials when it: (1) is limited to identification purposes; (2) applies to victims of crime; (3) involves a suspicion that injury or death has occurred because of criminal conduct; (4) is needed in a criminal investigation; (5) necessary to prevent or lessen the threat to the health or safety of a person or to the public; (6) in response to a valid court order; (7) to identify or locate a suspect, fugitive or missing person; (8) to report a crime on our premises; or (9) is Required by Law.
Emergency or Disaster. If the President declares an emergency or disaster, and the Secretary of HHS declares a public health emergency, the Secretary may waive our obligation to comply with any or all of the following Privacy requirements to: (1) obtain the patient's agreement to speak to family members or friends involved in the patient's care; (2) honor a request to opt out of the facility directory; (3) distribute a Notice of Privacy Practices; (4) patient's right to request privacy restrictions; or (5) the patient's right to request confidential communications. Waiver only applies if the Hospital is in the emergency area for the emergency period and for up to 72 hours until the Hospital implements its disaster protocol.
Prevent Threat of Serious Harm. We may disclose PHI if a reasonable belief exists that it may prevent or lessen a serious and imminent threat to the health or safety to you, another person, or the public, and disclosure is made to a person(s) reasonably able to prevent or lessen the threat, including the target of the threat.
Proof of Immunization. We may disclose PHI to schools for the limited purpose of showing proof of immunization of a student or prospective student, and the parent, guardian, person acting in loco parentis, or emancipated minor does not object.
Organ and Tissue Donation. If you are an organ or tissue donor, we may disclose medical information to the organizations that handle: (1) organ procurement; (2) organ, eye, or tissue transplantation; or (3) an organ donation bank, as applicable, to facilitate organ or tissue donation and transplantation.
Correctional Institution or Custody. If you are an inmate of a jail, prison, correctional institution, or under the custody of law enforcement officials, we may release medical information about you for purposes of: (1) the institution's providing you with health care; (2) protecting your health and safety and the health and safety of others; and (3) protecting the safety and security of the correctional institution or custodial facility.
Your Rights
You have the Right to Request Restrictions on Certain Uses and Disclosures of PHI
You may request that we do not disclose certain PHI to family members, personal representatives, friends or others. HIPAA's Privacy Rule gives hospitals and doctors the right to deny a patient's request to restrict the use or disclosure of PHI when it is being used or disclosed to other covered entities for treatment purposes.
We will honor your request to restrict the use or disclosure of PHI when submitting a claim to insurance or health plan for reimbursement if you agree in writing to pay out-of-pocket the claim in full. We will consider all other requests for restricted use or disclosure of PHI on a case-by-case basis. If we cannot accommodate your request, we will let you know.
You have a Right to Access, Inspect, and Receive a Copy of Your Own PHI
Generally, you have the right to inspect and have a copy of your own PHI in our records maintained as a "designated record set." There are exceptions. You may not have the right to inspect or copy psychotherapy notes or information compiled for civil, criminal or administrative proceedings. Your right may not extend to information covered by other laws or information obtained from someone other than another health care provider. We may deny access if, in our judgment, seeing that information could endanger the life or safety of you or another. We may charge you at the rate the law permits for copying records.
You may request access to your PHI in writing and giving or sending it to us. We will consider all requests according to our legal responsibilities under the privacy rule.
We usually will respond within 30 days from when we receive the request. Sometimes, it may take more than 30 days in which case we will act as soon as reasonably practical. If we grant your request, we will set up an appointment for you to inspect your PHI.
If you request access to PHI that is maintained in an electronic record or electronic designated data set, we will provide an electronic "machine readable copy" in a standard format enabling the ePHI to be processed and analyzed by a computer in a manner that accommodates Individual requests for specific formats.
Alternatively, you may ask for a written summary of your health information instead of inspecting or copying your records. We may charge you for a summary. If we are unable to grant your request, we will notify you in writing of the basis for the denial and your rights for review.
You have the Right to Amend Incorrect or Incomplete Facts in Your PHI
You may request that incorrect or incomplete PHI in your record be amended by contacting our Privacy Officer at (330) 596.7161, or mailing your request to us. We will respond to your request within 60 days from when we receive your written request.
We will grant your request if PHI that we created is incorrect or incomplete. We will not amend your health information if it is not part of a designated record set or was not created by us, if it would not be available for you to inspect, or if the information is accurate and complete.
If we grant your request, we will amend the PHI in the designated record set. We will inform you that we have made the amendment, and we will inform persons who have received and may have relied on PHI that it has been amended.
If we deny your request, we will: (1) tell you in writing the reason for denial; (2) inform you of your right to submit a written statement of disagreement, which we will keep with your record and will include with future disclosures; and (3) inform you of your right to file a complaint. If you file a statement of disagreement, we may prepare a written rebuttal. If you have questions about this right, please contact our Privacy Officer at (330) 596.7161.
You have a Right to Receive an Accounting of Disclosures of Health Information
You have a right to receive an accounting of disclosures we have made to others of your PHI up to six years prior to the date in which the request for an accounting is made. There are certain exceptions and limitations, including, but not limited to disclosures made: (1) for treatment, Health Care Operations, or Payment; (2) to the Individual (or Personal Representative) of his or her own PHI; and (3) according to a signed Authorization.
You may request an accounting of disclosures by contacting our Privacy Officer at (330) 596.7161. The first accounting you request within a 12-month period will be free. For additional accountings, we may charge you for the cost of preparing the list.
The accounting will include the date of disclosure of PHI; the name of the third-party to whom PHI was disclosed; if known, the address of the third-party; a brief description of the disclosed PHI; and a brief explanation of the purpose for disclosure.
Your Have a Right to Receive a Breach Notification
We will promptly notify you by first-class mail, at your last known address, if we discover a breach of Unsecured PHI, which includes the unauthorized acquisition, access, use, or disclosure of your PHI, unless we determine by Risk Assessment that a low probability exists that the compromise of your PHI would cause you financial, reputational, or other harm. We will include in the breach notification a brief description of what happened, a description of the types of unsecured PHI involved, steps you should take to protect yourself from potential harm, a brief description of what we are doing to investigate the breach and mitigate potential harm, as well as contact information for you to ask questions and learn additional information.
Health Information Exchange
We, along with other area hospitals, physicians, and health care providers may participate in a Health Information Exchange (HIE), which allows covered entities to share patient information electronically for treatment purposes. An HIE is considered a business associate and is required to safeguard the privacy and security of your PHI.
Only health care providers caring for you, or who may be involved in your care, may access PHI from the HIE. Administrative, physical and technical safeguards, such as password protection, encryption, audit and tracking capability, that comply with HIPAA and other privacy laws protect the privacy and security of your PHI in the HIE.
We are committed to protecting your PHI. Despite our best efforts, questions, concerns, or problems may arise. If you have a concern, or you believe that your privacy rights have been violated or breached, we encourage you to contact us immediately. You may send us a written complaint, or call our Privacy Officer at (330) 596.7161.
We take all concerns and complaints very seriously and will investigate each one promptly. If we made a mistake or learn of an unauthorized disclosure or breach, we will do what we can to correct it and take steps to prevent such mistakes or problems in the future. If we did not make a mistake, we will provide you with an explanation. Either way, we will make every effort to get back to you within 30 days.
We will never retaliate against you for expressing a concern or filing a complaint relating to your privacy rights. If you are not satisfied by our response, you may contact the Office for Civil Rights of the Department of Health and Human Services in Washington, D.C. in writing within 180 days of the suspected violation or breach.
Changes to this Notification of Privacy Practices
We reserve the right to change this notice at any time, which we may make effective for PHI we already used or disclosed, and/or for any PHI we may create, receive, use, or disclose in the future. We will make material amendments based on changes in the HIPAA laws.
We will post a current version of our Notice of Privacy Practices (with the effective date) on our website and at Alliance Community Hospital and its health provider affiliates listed above. You may request a paper copy of the notice whenever you come for treatment or at any time by calling 330-596-6000.
Effective 5-15-2015


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Minor League Depth — Catcher
This is the first of a series covering the Pirates' minor league depth position by position. The idea is to take a look at the players the system has available at a position, level by level. No organization has prospects at every position and every level. It's interesting to see just how well the Pirates are covered at each spot by players who at least have some chance to turn into major leaguers, and how many spots will have to be manned by organizational players.
The first installment covers the catchers. As we all saw in 2011, a team can run through its catching depth in a hurry. This can happen in the minors as well as the majors; it's not unusual for a team to have to pick up a catcher or two late in the season to fill vacancies created by injuries and/or promotions. The Pirates ha...
This content is for Pirates Prospects subscribers only. Subscribers get access to all of our daily articles on the Pirates and their minor league system, with live coverage throughout the system on a daily basis. Our lowest rates are $2.22 per month under our Top Prospect Plan, which also gets you a 40% discount on the 2017 Prospect Guide. Subscribe today to access all of our daily coverage of the Pirates' system.
If you're already a member, you can log in below. If you think you're receiving this message in error, please e-mail email@example.com.
Wilbur Miller joined the site in July 2010. He has long been known for his excellent Player Profiles, which he brought to the site in February 2011, combining them with the existing Pirates Prospects Player Pages. Wilbur maintains the player pages section of the site, and provides regular articles to the main portion of the site, including a weekly Prospects Trend piece, featuring the best and worst prospects from the previous week.
My guess is Lindblom stays with Indianapolis, though I'm not…
MLB should fine umps for such blatant incompetence. Makes one…


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Director's Desk
Positive Thinking is a Way of Life to get what you want
Positive thinking is a mental and emotional attitude that focuses on the bright side of life and expects positive results. A positive person anticipates happiness, health and success, and believes he or she can overcome any obstacle and difficulty. According to Remez Sasson, Positive thinking is not a concept that everyone believes and follows. Some, consider it as nonsense, and scoff at people who follow it. However, there is a growing number of people, who accept positive thinking as a fact, and believe in its effectiveness. It seems that this subject is gaining popularity, as evidenced by the many books, lectures ... Read More
- Positive Thinking is a Way of Life to get what you want
- The Other Half of Communication is Listening
- ALMA Paces Ahead to Motivate Youth Empowerment through Education
- Grow and Succeed Through Generating Self Improvement
- The past is dead and gone and today is all you have
- Not Much Happens Without a Dream
- Time does not change things, we do
- Measure Your Degree of Persistence
- Don't follow the crowd
- Success is a daily habit
- Steps to Evolving a Passion and Making it Work
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- Do you have a winning attitude at work and in business?
- The Certainty of Success
- Alma Wishes You Happy New Year…!


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By Steve Stone for MSNsportsNET.com
April 25, 2009
TAMPA, FLA. - Six runs given up in the first two innings put the West Virginia University baseball team in an early bind as it fell to BIG EAST leader USF, 11-2, on Saturday evening at Red McEwen Field in Tampa, Fla.
The Mountaineers (28-11, 11-6) fall into a third-place tie in the BIG EAST with St. John's, but hold the tiebreaker after defeating the Red Storm in two of three games at Hawley Field.
USF right-hander Derrick Stultz (5-1) earned the victory after giving up two runs on six hits in eight innings pitched. He received plenty support from an offense that recorded 18 hits overall, tied for the most that WVU has given up in 2009.
WVU starter Billy Gross (5-4) took the loss after giving up nine runs on 15 hits in 4.2 innings. The right-hander from Frederick, Md., did not allow a hit to three of his four leadoff hitters, but was unable to throw his offspeed pitches effectively and finished the outing with no strikeouts against a high-contact Bulls (26-15, 14-3) squad.
WVU used four pitchers overall, as Jesse Darby, Justin Ellis and Andy Podolinski allowed just two runs combined in relief. Darby entered the game with two outs in the fifth and struck out USF's Stephen Hunt looking. Ellis and Podolinski combined to give up one run on two hits in three innings pitched.
Dan DiBartolomeo led the Mountaineers with two hits, including his 14th double of the season. The Margate, N.J., native is among the conference leaders with a .430 batting average.
WVU began the game well by scoring one run in the first inning. Justin Parks led off with a single through the left side, and Austin Markel followed with a single to right field to advance Parks to third base. Jedd Gyorko hit a sacrifice fly to right field to bring in Parks, making it 1-0.
USF responded with a run of its own in the bottom half, as Todd Brazeal hit an RBI groundout to tie the game at 1-1.
The Bulls hit six singles in the second inning to propel their five-run outburst. Peter Brotons hit an RBI single up the middle, and Ryan Lockwood followed with another run-scoring hit up the middle to give USF a 3-1 advantage. Jonathan Koscso added an RBI single, and Brazeal finished the scoring with an RBI of his own to extend USF's lead to 6-1.
In the fifth, Brotons added a run-scoring single and Lockwood followed with a triple down the first base line to bring in another run. WVU countered with a run in the sixth inning on a run-scoring groundout by Vince Belnome, who tallied his conference-leading 60th RBI of the season.
USF came back in the sixth with an RBI double to center field by Trey Manz to give the Bulls a 10-2 lead. Junior Carlin then sliced an opposite-field single to left field to make it 11-2.
The Mountaineers will try to salvage their three-game set on Sunday when they face USF at 1 p.m. at Red McEwen Field.


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There were powerful women in Bible times. Some were godly, others were not. But nowhere in the Bible is there an indication that God did not approve of these women leaders because they were female.
This article looks especially at the queen of the South (mentioned in the Old Testament and the gospels) and Bernice (mentioned in the book of Acts). Continue reading»


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Feminism | Posted by Gina H on 01/6/2014
Recovering from an Abusive Relationship
After I escaped my abusive relationship I overexerted and exhausted myself at my own expense for the sake of resolving public opinion. I felt I needed to explain why I had been behaving so differently. I wanted to make sure people knew what had really been happening behind closed doors and that it was out of my control. I felt I needed to let other people in, to make them understand, sympathize and care.
I believe this was a mistake, and one that isn't often discussed. Nobody should feel that they need to protect their abuser's image. You are hurting yourself in doing that. Your abuser is not fighting for your reputation. Most likely, they are saying whatever they can to negate you, to prove you wrong, to label you as jealous or obsessive or what have you. Remember that these attempts aren't about you, personally, but that people who try to sabotage others' images are at war with themselves. If your abuser succeeds and other people believe them, don't take it to heart and don't emotionally exhaust yourself trying to change their minds. They will never know what really happened and the sad truth is abuse doesn't make sense to and is hard to accept for many, especially if the abuser is someone they know, love and party or work with.
The main thing I've realized after escaping an abusive relationship is that one's experience is no one else's but their own: you alone have been exposed to this. You are the only one who will ever know exactly what happened between the two of you and why. You may be panicked. You are probably genuinely scared for people he will continue to hurt in his life. You are distraught with worry. Is he really going to get away with this?
I urge you to consider this: use your knowledge of the truth, of what really happened, not to defeat you, but to reignite your indelible passion for life. If you are like me, so much of your time and hunger and excitement for learning has been cruelly taken away. Now is the time to experience the joy of getting it back. Delve into knowledge now. Be a student. Revitalize your mind and heart with everything you'd been missing out on while your abuser had you under their control. You're free and get to stay the fuck away from their manipulative control and run full-speed ahead toward the things you've always wanted to do in your life. Write, paint, explore, kiss someone genuinely sweet, make new friends, get lost in a really delicious book, get involved in the community, reconnect with someone you loved and lost along the way, experience the bliss in solitude and promise yourself you'll accept only the ultimate kindness and respect from others.
View this not as the end of a horrible experience but the begging of a fantastic new one. Be warmed with peace knowing that it's finally over and that you have done everything in your power to make the best of a bad situation.
Let go of any need to justify the way you chose to face your abuse. A vital key to finding happiness after abuse is that we must accept that some people are disturbed, ugly, violent, fake, and manipulative. I hate this. These words are so tough to write because I will always be an eternal optimist and a believer in people. But charm is deceptive. It is a tool that works. It is such an ugly lesson to learn in life. I have had the hardest time learning this for myself. Reality can be dark and we typically subject ourselves only to what we want to see or believe; however, when that precious, esteemed image of life and others is disturbed or shaken, we completely lose our sense of self. We get lost in our inability to understand this new abrupt image.
Let's cut to the heart of abuse: it begins when our psyche is intruded, invaded, threatened, twisted and jerked around in any kind of repetitive cycle. Afraid of this sudden invasive energy, we stop thinking for ourselves and we stop acting like ourselves. We start to send mixed signals and push people away. Over time, our belittlement becomes severe, and we even begin to lie for our abusers to keep their reputation whole. We build them up not just to protect them, but also ourselves, so that we can use it as a tool to justify being with them when it's just the two of us alone and the abuse is obvious. We subject ourselves to their demands, as cruel and perverted as they are. We do anything.
But in the end, you must save yourself. Joy is only possible if you allow yourself to see the sickness and perversion in your abuser. It is not your fault. You were targeted, taken advantage of, used, manipulated, charmed or threatened after every attack, constantly submitted to a cycle of twisted, unprecedented, perverse behavior. You should be confused. You had every right to be confused while you were with him.
In your innocence, you sought explanation. You sought justification. You sought to see anything other than the truth. You tried to look for the best. But you eventually accepted the signs of abuse, found your strength, and did what you had to do to protect yourself, and that's what matters.
Some abusers will stop at nothing to win control. Some will never be able to see anything wrong with the way they treated you. Some are incapable of self-blame. They are excellent at convincing others they are the victim. These abusers are not healthy – perhaps they struggle with depression, narcissism or addiction. It is necessary for victims to know deep within their hearts that these things are out of their control. You could not have known.
I reiterate: it is not your fault. These things happen. I can only wonder why they do. I have my beliefs. Form yours. Allow yourself that inevitable period of questioning. Embrace your confusion. Embrace your hurt. Embrace your disappointment. Acknowledge your pain. Do not let it swallow you. Do not let it devour your beautiful, vivacious, creative hunger for life. Renew your strength. Kick life right back in the balls. Be fabulous. Recognize this experience not as a setback, but as an opportunity for a comeback — you can come back in any way, shape, or form that you please. Be adventurous with your new you.
Originally posted on Happiness Enlisted
Read other posts about: abuse, abusive relationship, domestic abuse, Feminism, feminist relationships, relationships
Post Your Comment
Monika_K @ at 9:49 am, January 8th, 2014
Dear Gina, thank you very much for this article. I was crying while I was reading it. You have just opened my eyes. I experienced everything you write about. However, now I know that I was psychically abused.
I wish each woman is self-confident enough to be herself in whatever situation. Good luck, Gina!