text:
P- Reviewers Kumar V, Wang B S- Editor Wen LL L- Editor A E- Editor Li JY
Published online Jun 27, 2013. doi: 10.4254/wjh.v5.i6.302
Revised: May 15, 2013
Accepted: May 18, 2013
Published online: June 27, 2013
Management of hepatocellular carcinoma (HCC) has been continuously evolving during recent years. HCC is a worldwide clinical and social issue and typically a complicates cirrhosis. The incidence of HCC is increasing, not only in the general population of patients with cirrhosis, but particularly in some subgroups of patients, like those with human immunodeficiency virus infection or thalassemia. Since a 3% annual HCC incidence has been estimated in cirrhosis, a bi-annual screening is generally suggested. The diagnostic criteria of HCC has recently had a dramatic evolution during recent years. HCC diagnosis is now made only on radiological criteria in the majority of the cases. In the context of cirrhosis, the universally accepted criteria for HCC diagnosis is contrast enhancement in arterial phase and washout in venous/late phase at imaging, the so called "typical pattern". However, recently updated guidelines slightly differ in diagnostic criteria. Apart from liver transplantation, the only cure of both HCC and underlying liver cirrhosis, all the other treatments have to match with higher rate of HCC recurrence. The latter can be classified into curative (resection and percutaneous ablation) and palliative treatments. The aim of this paper was to review the current knowledge on management of HCC and to enlighten the areas of uncertainty.
Core tip: Management of hepatocellular carcinoma (HCC) has been continuously evolving during recent years. The aim of this paper was to review the current knowledge on management of HCC and to enlighten the areas of uncertainty.
Citation: Mancuso A. Management of hepatocellular carcinoma: Enlightening the gray zones. World J Hepatol 2013; 5(6): 302-310
Management of hepatocellular carcinoma (HCC) has been continuously evolving during recent years. However, albeit overall similar, the main Societies of Hepatology differently defined their own guidelines. In fact, despite an evident agreement in the general lines of HCC management, some gray zones still persist[1-4]. The aim of this paper was to review the current knowledge on management of HCC and to enlighten the areas of uncertainty.
HCC is a worldwide clinical and social issue. Actually, it is the sixth most common cancer and the third cause of cancer-related death. Incidence increases with advancing age, with a median age at onset of about 70 year-old in developed countries and there is a male preponderance, with a male to female ratio of about 2.4[5,6].
HCC is typically a complication of cirrhosis, although it can rarely develop in the absence of cirrhosis[1-4]. Known underlying diseases at risk for HCC development are chronic viral hepatitis C and B, alcoholic hepatitis, non- alcoholic fatty liver disease, autoimmune hepatitis, hemochromatosis, alpha-1-antitrypsin deficiency, Wilson's disease, Budd-Chiari syndrome (BCS). Diagnostic algorithm follows the same radiological criteria for HCC (see above) despite the different aetiologies of underlying liver disease. However, an exception is HCC developing in BCS. In fact, the radiological pattern of regenerative nodules in BCS is similar to that of HCC[7]. Moreover, as a consequence of the hindered hepatic venous outflow, radiological criteria for HCC can be altered[8,9]. Finally, although the risk of procedure-related bleeding is probably increased[10], generally diagnosis of HCC in BCS still needs histological confirmation[8,9].
Overall, the incidence of HCC is increasing, not only in the general population of patients with cirrhosis[11,12], but particularly in some subgroups of patients, like those with human immunodeficiency virus (HIV) infection or thalassemia. In fact, in both HIV and thalassemia, a recent significant outcome improvement due to, respectively, iron chelating drugs in the latter and highly active antiretroviral therapy in the former, has allowed the appearance of the complication of the underlying hepatic disease[13-18].
Surveillance of HCC is important simply because as little is HCC size at diagnosis as high is the probability of curative treatment. Since a 3% annual HCC incidence has been estimated in cirrhosis[19], a bi-annual screening is generally suggested[1-4]. Although less stringent, there is a risk of HCC development also in non-cirrhotic chronic hepatitis and treated viral hepatitis, for which an annual screening is generally performed[1-4]. Ultrasound (US) is the test of choice for surveillance. In fact, US is a cheap and safe test, due to the absence of contrast medium and radioactivity[20-23]. Moreover, differently from computed tomography (CT) and magnetic resonance (MR), US does not expose to the risk of false positive results. However, CT or MR should be preferred for surveillance of patients for which US is not adequate because of technical reasons or in liver transplantation (LT) waiting list[1-4].
Once hepatic nodules are discovered at US screening, the further work-up depends on the size[1-4]. Nodules < 1 cm should prompt a strict US surveillance every 3 or 4 mo for the first year and, in the absence of size increase, every six months after one year, like patients with cirrhosis without liver nodules. In fact, hepatic nodules < 1 cm rarely are HCC. Moreover, for such little size nodules, diagnostic value of either CT and MR is inadequate.
Nodules between 1 and 2 cm in size should be studied with CT and MR and, in case of non diagnostic imaging, undergo nodule biopsy. Moreover, a second biopsy should be contemplated in case of inconclusive findings at histology, nodule growth or change in enhancement pattern.
Nodules > 2 cm should undergo CT and MR and, in case of atypical imaging findings, nodule biopsy[1-4].
The diagnostic criteria of HCC has recently had a dramatic evolution during recent years[1-4,24]. In fact, till the first half of the past decade, the Golden Standard for HCC diagnosis was histology. Then, since radiological diagnostic criteria have been shaped and established[1], HCC diagnosis is now made only on radiological criteria in the majority of the cases[1-4]. In the context of cirrhosis, the universally accepted criteria for HCC diagnosis is contrast enhancement in arterial phase and washout in venous/late phase at imaging, the so called "typical pattern" (Figures 1-3). However, recently updated guidelines slightly differ in diagnostic criteria[2-4].
Hepatic lesions > 1 cm with typical pattern at one imaging (CT or MR) have diagnosis of HCC in both the American Association for the Study of Liver Disease (AASLD) 2011 and European Association for the Study of the Liver (EASL) 2012 guidelines[2,4]. However, EASL 2012 guidelines specify that for lesions between 1 and 2 cm the concordance of typical pattern at two imaging (CT and MR) should be advices in suboptimal settings (technology, local skills)[4]. Both AASLD 2011 and EASL 2012 guidelines suggest lesion biopsy in the absence of typical pattern. Finally, both AASLD 2011 and EASL 2012 guidelines exclude from diagnostic criteria contrast-enhanced US (CEUS) and alpha-fetoprotein value[2,4].
Japanese Society of Hepatology (JSH) 2012 guidelines agree with the diagnostic value of typical pattern at one imaging (CT, MR, CEUS) regardless of the size, and maintains the diagnostic value of CEUS and biochemistry (AFP > 200 ng/dL, PIVKA-II > 40, AFP L3 > 15%)[3]. However, the main difference between JSH 2012 and both AASLD 2011 and EASL 2012 guidelines is that the former consider a diagnostic criteria the lesion hypo-intensity in hepatic image of Gd-EOB-MR[2-4].
Apart from LT, the only cure of both HCC and underlying liver cirrhosis, all the other treatments have to match with higher rate of HCC recurrence. The latter can be classified into curative (resection and percutaneous ablation) and palliative treatments[2-4].
Resection is considered the First-Line treatment for patients with solitary tumours and preserved liver function (normal bilirubin and, either HVPG ≤ 10 mmHg, PLT > 100000 or no varices at endoscopy). Resection can also be performed for multi-focal HCC inside Milan criteria or in case of mild portal hypertension when patients are not suitable for orthotopic LT (OLT), although it is debated if such patients could benefit from other locoregional therapies, avoiding the risk of surgery and of liver de-compensation after surgery. In fact, perioperative mortality in cirrhotics after HCC resection is about 2%-3%. Moreover, there is a risk of tumor recurrence after surgery of about 70% at 5 years, enclosing both true recurrence and the novo tumours[25-39].
Percutaneous local ablation, namely radiofrequency ablation (RFA) and ethanol injection (EI) are the standard of care for BCLC O-A not suitable for surgery. Although RFA is recommended in most instances as the main ablative therapy in tumors less than 5 cm, the probability of complete necrosis is very high for little tumors (< 2 cm) and progressively decreases with the increase of tumor size. In tumours ≤ 2 cm both RF and EI achieve complete responses in more than 90%, making percutaneous local ablation competitive with resection. EI is better indicated when RFA in not technically feasible. This is the case of tumors overflowing the liver margin or near organs, just like gallbladder or bowel, because of the risk of thermal injury and perforation, or when tumor is adjacent to a main vessel, because of the concern of thermal dispersion and inefficacy of RFA[40-64].
Trans-arterial chemoembolization (TACE) is the recommended treatment for BCLC stage B multinodular asymptomatic tumors without vascular invasion or extrahepatic spread. Drug-eluting beads have similar efficacy to gealfoam-lipiodol with probably less adverse events. Both should be discouraged in decompensated liver disease and in case of macroscopic vascular invasion or extrahepatic spread[65-80]. An alternative to TACE is radioembolization. However, radioembolization , although promising and with advantage of being indicated also in the case of portal vein neoplastic thrombosis, is expensive and further data are needed. In fact, to our knowledge there are not well designed studies comparing radioembolization with neither TACE nor sorafenib[81-84].
LT is actually a consolidated therapeutic option for HCC because it cures both tumor and underlying cirrhosis[1-4]. However, the indication of LT for HCC treatment has evolved over recent years[85-109]. Moreover, initial experiences tended to offer LT as the last therapeutic chance when resection was not feasible. In fact, till the first half of nineties, the discouraging results of some experiences had questioned the possibility of LT efficacy as HCC treatment. In 1996, the publication of a pivotal prospective study on less than 50 patients, transplanted for HCC under predefined criteria (single HCC ≤ 5 cm or 3 HCC ≤ 3 cm each), the so called "Milan criteria", showed a 4-year survival of 75%[85]. Subsequent experiences of LT for HCC inside the Milan criteria, confirmed a survival rate exceeding 70% at 5 years, with a recurrence in less than 15%. Due to these data, LT is now the first-line treatment for one HCC ≤ 5 cm or 3 HCC ≤ 3 cm each[1-4].
Although all published guidelines go on considering the Milan criteria as the only fence inside which LT should be considered as treatment of HCC[2-4], the possibility of an extension of Milan criteria as indication for LT is already a debated issue. In fact, while it is universally recognized that LT for HCC inside Milan criteria guaranties an acceptable outcome, numerous heterogeneous experiences explore the possibility of extending the Milan criteria.
A line of experiences studies the applicability of the University of California San Francisco (UCSF) criteria, that is single nodule ≤ 6.5 cm or 2-3 nodules ≤ 4.5 cm and total diameter ≤ 8 cm. In fact, UCSF criteria on explant identified retrospectively a cohort of patients whose survival was not significantly different from those of patient transplanted for HCC inside the Milan criteria[93]. The same results had other retrospective experiences by other groups using UCSF criteria. Moreover, a recent prospective study showed a 5-year survival not significantly different in patients transplanted for HCC inside Milan and UCSF criteria[103].
A recent multicenter restrospective study on over 1700 found that HCC inside the "up-to-seven" criteria at explant (those HCCs having the number 7 as the sum of the size of the larger tumor and the number of tumors) and without microvascular invasion had a 5-year survival not significantly different from those inside the Milan criteria, while survival was significantly worst in case of HCC inside the "up-to-seven" criteria and with microvascular invasion[104].
Another line of studies suggest that down-staging for HCC exceeding conventional criteria could be effective for extending LT without worsening survival. These studies are heterogeneous in design, inclusion criteria and philosophy. In fact, while some suggests to offer LT to those patients who achieve an effective downstaging, so selecting patients with a less aggressive HCC and likely reducing the probability of HCC recurrence after LT, others indicate LT for those HCC without an effective downstaging, as a rescue treatment[107-109].
Despite all the above studies, guidelines still give indication to LT only to HCC inside Milan criteria[2-4]. However, as published experiences show, many center actually perform LT outside the Milan criteria, using criteria different from centre to centre[85-109].
Whatever the criteria adopted, a significant problem of HCC candidates for LT is the drop out, that is patients who do not reach the goal of LT because of progression of HCC or of causes unrelated to HCC. Many studies have investigated the risk of drop out that remains difficult to define, although some factors, like tumor multinodularity, neoadjuvant treatment failures, elevated AFP or model for end-stage liver disease score, have been correlated with a higher probability of drop out. From an opposite point of view, given the organ shortage, some patients with single HCC < 2 cm may benefit from alternative treatments and avoid LT at least until recurrence occours, highlighting the possibility of salvage transplantation in low risk population. Moreover, it is still uncertain which is the role of LT after surgery and high risk of recurrence at pathology[2-4].
Living donor LT (LDLT) is an alternative option if waiting list is long and offers the possibility of a LT after a short time. However, there is a donor risk of death of about 0.3% and of life threatening complications of about 2%. In fact, LDLT should be restricted to centers of excellence[110-120].
The mainstay of palliative therapy for advanced HCC is Sorafenib, which is indicated in advanced HCC (BCLC C) or HCC progressing upon loco-regional therapies in patients with well preserved liver function and good performance status. Registrative studies have shown a 3-mo increase in median overall survival of sorafenib compared to placebo. Moreover, adverse events are frequent a can be severe (Diarrea, Hand-foot skin-reaction)[121-125].
The role of Sorafenib in some subgroup of patients is debated. In fact, while some experiences report encouraging results of sorafenib therapy after HCC recurrence post OLT, others suggests that adverse events could affect sorafenib efficacy[126-135]. Moreover, our preliminary experience on HCC in HIV positive patient report a high incidence of hepatotoxicity. In both the subgroup the possibility of drug interections should be investigated.
I thank Prof Angelo Vanzulli for imaging supply.
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|Lin DY, Liaw YF, Lee TY, Lai CM. Hepatic arterial embolization in patients with unresectable hepatocellular carcinoma--a randomized controlled trial. Gastroenterology. 1988;94:453-456. [PubMed]
|Pelletier G, Roche A, Ink O, Anciaux ML, Derhy S, Rougier P, Lenoir C, Attali P, Etienne JP. A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J Hepatol. 1990;11:181-184. [PubMed] [DOI]
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|Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology. 2004;127:S179-S188. [PubMed] [DOI]
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|Goldberg SN, Grassi CJ, Cardella JF, Charboneau JW, Dodd GD, Dupuy DE, Gervais DA, Gillams AR, Kane RA, Lee FT. Image-guided tumor ablation: standardization of terminology and reporting criteria. J Vasc Interv Radiol. 2009;20:S377-S390. [PubMed] [DOI]
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|Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)-embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev. 2011;CD004787. [PubMed] [DOI]
|Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010;33:41-52. [PubMed] [DOI]
|Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52-64. [PubMed] [DOI]
|Kulik LM, Carr BI, Mulcahy MF, Lewandowski RJ, Atassi B, Ryu RK, Sato KT, Benson A, Nemcek AA, Gates VL. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008;47:71-81. [PubMed] [DOI]
|Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, Heusner T, Cicinnati VR, Paul A, Bockisch A. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52:1741-1749. [PubMed] [DOI]
|Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Marchianò A, Bongini M, Lanocita R. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013;57:1826-1837. [PubMed] [DOI]
|Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003;37:429-442. [PubMed] [DOI]
|Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693-699. [PubMed] [DOI]
|Mela M, Mancuso A, Burroughs AK. Review article: hepatocellular carcinoma: indications for liver transplantation. Aliment Pharmacol Ther. 2003;17 Suppl 2:130-137. [PubMed] [DOI]
|Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13:e11-e22. [PubMed] [DOI]
|Iwatsuki S, Starzl TE, Sheahan DG, Yokoyama I, Demetris AJ, Todo S, Tzakis AG, Van Thiel DH, Carr B, Selby R. Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg. 1991;214:221-228; discussion 228-229. [PubMed] [DOI]
|Iwatsuki S, Esquivel CO, Gordon RD, Shaw BW, Starzl TE, Shade RR, Van Thiel DH. Liver transplantation for fulminant hepatic failure. Semin Liver Dis. 1985;5:325-328. [PubMed] [DOI]
|Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 1999;19:311-322. [PubMed] [DOI]
|Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg. 1993;218:145-151. [PubMed] [DOI]
|Jonas S, Bechstein WO, Steinmüller T, Herrmann M, Radke C, Berg T, Settmacher U, Neuhaus P. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080-1086. [PubMed] [DOI]
|Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394-1403. [PubMed] [DOI]
|Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D'Amico G, Dickson ER, Kim WR. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464-470. [PubMed] [DOI]
|Pomfret EA, Washburn K, Wald C, Nalesnik MA, Douglas D, Russo M, Roberts J, Reich DJ, Schwartz ME, Mieles L. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262-278. [PubMed] [DOI]
|Sala M, Fuster J, Llovet JM, Navasa M, Solé M, Varela M, Pons F, Rimola A, García-Valdecasas JC, Brú C. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transpl. 2004;10:1294-1300. [PubMed] [DOI]
|Mazzaferro V, Battiston C, Perrone S, Pulvirenti A, Regalia E, Romito R, Sarli D, Schiavo M, Garbagnati F, Marchianò A. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg. 2004;240:900-909. [PubMed] [DOI]
|Lu DS, Yu NC, Raman SS, Lassman C, Tong MJ, Britten C, Durazo F, Saab S, Han S, Finn R. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology. 2005;41:1130-1137. [PubMed] [DOI]
|Majno PE, Adam R, Bismuth H, Castaing D, Ariche A, Krissat J, Perrin H, Azoulay D. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg. 1997;226:688-701; discussion 701-703. [PubMed] [DOI]
|Decaens T, Roudot-Thoraval F, Bresson-Hadni S, Meyer C, Gugenheim J, Durand F, Bernard PH, Boillot O, Boudjema K, Calmus Y. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl. 2005;11:767-775. [PubMed] [DOI]
|Porrett PM, Peterman H, Rosen M, Sonnad S, Soulen M, Markmann JF, Shaked A, Furth E, Reddy KR, Olthoff K. Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl. 2006;12:665-673. [PubMed] [DOI]
|Llovet JM, Mas X, Aponte JJ, Fuster J, Navasa M, Christensen E, Rodés J, Bruix J. Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut. 2002;50:123-128. [PubMed] [DOI]
|Yao FY, Xiao L, Bass NM, Kerlan R, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587-2596. [PubMed] [DOI]
|Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35-43. [PubMed] [DOI]
|Raj A, McCall J, Gane E. Validation of the "Metroticket" predictor in a cohort of patients transplanted for predominantly HBV-related hepatocellular carcinoma. J Hepatol. 2011;55:1063-1068. [PubMed] [DOI]
|Schwartz M, Dvorchik I, Roayaie S, Fiel MI, Finkelstein S, Marsh JW, Martignetti JA, Llovet JM. Liver transplantation for hepatocellular carcinoma: extension of indications based on molecular markers. J Hepatol. 2008;49:581-588. [PubMed] [DOI]
|Yao FY, Kerlan RK, Hirose R, Davern TJ, Bass NM, Feng S, Peters M, Terrault N, Freise CE, Ascher NL. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48:819-827. [PubMed] [DOI]
|Ravaioli M, Grazi GL, Piscaglia F, Trevisani F, Cescon M, Ercolani G, Vivarelli M, Golfieri R, D'Errico Grigioni A, Panzini I. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant. 2008;8:2547-2557. [PubMed] [DOI]
|De Carlis L, Di Sandro S, Giacomoni A, Slim A, Lauterio A, Mangoni I, Mihaylov P, Pirotta V, Aseni P, Rampoldi A. Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation? J Clin Gastroenterol. 2012;46:78-86. [PubMed] [DOI]
|Trotter JF, Wachs M, Everson GT, Kam I. Adult-to-adult transplantation of the right hepatic lobe from a living donor. N Engl J Med. 2002;346:1074-1082. [PubMed] [DOI]
|Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007;356:1545-1559. [PubMed] [DOI]
|Siegler M, Simmerling MC, Siegler JH, Cronin DC. Recipient deaths during donor surgery: a new ethical problem in living donor liver transplantation (LDLT). Liver Transpl. 2006;12:358-360. [PubMed] [DOI]
|Ghobrial RM, Freise CE, Trotter JF, Tong L, Ojo AO, Fair JH, Fisher RA, Emond JC, Koffron AJ, Pruett TL. Donor morbidity after living donation for liver transplantation. Gastroenterology. 2008;135:468-476. [PubMed]
|Brown RS. Live donors in liver transplantation. Gastroenterology. 2008;134:1802-1813. [PubMed] [DOI]
|Cronin DC, Millis JM. Living donor liver transplantation: The ethics and the practice. Hepatology. 2008;47:11-13. [PubMed] [DOI]
|Sarasin FP, Majno PE, Llovet JM, Bruix J, Mentha G, Hadengue A. Living donor liver transplantation for early hepatocellular carcinoma: A life-expectancy and cost-effectiveness perspective. Hepatology. 2001;33:1073-1079. [PubMed] [DOI]
|Lo CM, Fan ST, Liu CL, Chan SC, Ng IO, Wong J. Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma. Br J Surg. 2007;94:78-86. [PubMed] [DOI]
|Fisher RA, Kulik LM, Freise CE, Lok AS, Shearon TH, Brown RS, Ghobrial RM, Fair JH, Olthoff KM, Kam I. Hepatocellular carcinoma recurrence and death following living and deceased donor liver transplantation. Am J Transplant. 2007;7:1601-1608. [PubMed] [DOI]
|Kulik L, Abecassis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology. 2004;127:S277-S282. [PubMed] [DOI]
|Majno P, Mazzaferro V. Living donor liver transplantation for hepatocellular carcinoma exceeding conventional criteria: questions, answers and demands for a common language. Liver Transpl. 2006;12:896-898. [PubMed] [DOI]
|Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390. [PubMed] [DOI]
|Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25-34. [PubMed] [DOI]
|Kim JE, Ryoo BY, Ryu MH, Chang HM, Suh DJ, Lee HC, Lim YS, Kim KM, Kang YK. Sorafenib for hepatocellular carcinoma according to Child-Pugh class of liver function. Cancer Chemother Pharmacol. 2011;68:1285-1290. [PubMed] [DOI]
|Hollebecque A, Cattan S, Romano O, Sergent G, Mourad A, Louvet A, Dharancy S, Boleslawski E, Truant S, Pruvot FR. Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the Child-Pugh score. Aliment Pharmacol Ther. 2011;34:1193-1201. [PubMed] [DOI]
|Iavarone M, Cabibbo G, Piscaglia F, Zavaglia C, Grieco A, Villa E, Cammà C, Colombo M. Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy. Hepatology. 2011;54:2055-2063. [PubMed] [DOI]
|Fujiki M, Aucejo F, Kim R. Adjuvant treatment of hepatocellular carcinoma after orthotopic liver transplantation: do we really need this? Clin Transplant. 2013;27:169-177. [PubMed] [DOI]
|Sotiropoulos GC, Nowak KW, Fouzas I, Vernadakis S, Kykalos S, Klein CG, Paul A. Sorafenib treatment for recurrent hepatocellular carcinoma after liver transplantation. Transplant Proc. 2012;44:2754-2756. [PubMed] [DOI]
|Zavaglia C, Airoldi A, Mancuso A, Vangeli M, Viganò R, Cordone G, Gentiluomo M, Belli LS. Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature. Eur J Gastroenterol Hepatol. 2013;25:180-186. [PubMed] [DOI]
|Welker MW, Bechstein WO, Zeuzem S, Trojan J. Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge. Transpl Int. 2013;26:109-118. [PubMed]
|Vitale A, Boccagni P, Kertusha X, Zanus G, D'Amico F, Lodo E, Pastorelli D, Ramirez Morales R, Lombardi G, Senzolo M. Sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation? Transplant Proc. 2012;44:1989-1991. [PubMed] [DOI]
|Castroagudín JF, Molina-Pérez E, Ferreiro-Iglesias R, Abdulkader I, Otero-Antón E, Tomé S, Varo-Pérez E. Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed? Transplant Proc. 2012;44:1565-1567. [PubMed] [DOI]
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|Truesdale AE, Caldwell SH, Shah NL, Argo CK, Al-Osaimi AM, Schmitt TM, Northup PG. Sorafenib therapy for hepatocellular carcinoma prior to liver transplant is associated with increased complications after transplant. Transpl Int. 2011;24:991-998. [PubMed] [DOI]
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text:
July 31, 2012
|batterychargerstore.co.uk offers a range of award-winning smart chargers covering cars, motorcycles and other vehicles.
London, UK (rushPRnews) 07/31/12 — People who have recently purchased a second-hand vehicle and do not know the full history of its use would be wise to begin a battery maintenance routine in order to prolong the battery's life and ultimately save themselves money in the long-run, says leading smart charger brand, CTEK.
The car, motorbike or van may have experienced long periods of inactivity, meaning the battery cells could have become discharged. Or if it was used for short journeys and the battery did not often have the chance to fully charge, a high concentration of acid can result in stratification and therefore low battery plate conductivity. If conditions such as these are not remedied they will bring about the failure of a battery.
Not only can effective battery charging and care extend a battery's usage by as much as 300 per cent, but it also reduces the likelihood of not being able to start the vehicle due to a failed battery; the inconvenience and expense of buying a new battery, especially just after acquiring a second-hand vehicle is an annoyance that nobody would wish for. Optimising the performance of and reconditioning a battery though regularly using a smart charging device gives vehicle owners peace of mind about unexpectedly breaking down and the cost of replacing a battery.
Jan-Ulf Soderberg, head of brand and marketing at CTEK, comments: "A CTEK smart battery charger is ideal for someone who has just bought a second-hand car or motorbike and is not fully aware of how the vehicle was used and cared for day-to-day. Caring correctly for a vehicle's battery can prolong its life by up to 300 per cent and, of course, this means less expense and also fewer worries about being stranded with a failed battery.
"The MXS 5.0 for example, an eight step 12V battery charger, provides a battery diagnosis so owners can determine whether a charge can be received and held. Furthermore, it reconditions batteries that are deeply discharged or stratified and has optimised charging for periods of cold weather. Like many other chargers in the CTEK range, it also comprises a unique maintenance function and it can be left connected to the battery safely, even for long periods of time, while it continually tops up the charge to the ideal amount."
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subset: commoncrawl


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Western Byways is a magazine committed to the promotion of our "out-of-the-way" rural communities in our own backyards that make wonderful, economical travel destinations. This fosters a more productive local economy on all levels.
environment, living & lifestyle, travel & events
travel / hunting / local / hiking / driving / idaho / rural / outdoors / explore / byways / carey
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Hello, I'm CC! Starting February 2013, I will be leaving the life I know and starting my travels around the world. I'll be starting in Waimanalo, Hawaii as a WWOOFer on an organic farm. My unplanned plan is to live in Hawaii for 6 to 9 months then work my way to New Zealand. I'll be documenting everything on here and look forward to sharing the world through my eyes :-)
reading; listening to music; meeting new people; learning new cultures; most things outdoors
Haiti; New York City
Visiting: USA.
Visiting: USA.
Visiting: USA and Haiti.
CC Ya Later hasn't been active in the wiki travel guide yet. Have you?


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|Topic Review (Newest First)
Indie had a spay and gastropexy Wednesday. The vet said she needs to stay quiet for two weeks. Because of the gastropexy, the incision is pretty long. I keep her in crate full time right now. She acts like she's not sore at all but if I let her out, I know she will start playing too hard. We have been taking slow walks around the yard and up and down the street. It's hard keeping her calm. Just keep checking the incision.
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|I walked mine the day after her surgery . She never showed any signs of being fixed. The incision was not even a half inch and there was no stitches. I did not allow her to run or jump.
I've done a lot of spay-recovery in foster, and I don't think I'd take her out to walk today if she had surgery yesterday. I try to keep them very quiet (crate rest or the like) for about 3 days, then we do a little more up to the 7 day mark (including some light walking). After 7 days, if every thing is nice and dry and closed up, we start giving more freedom.
I've had some fosters who opened up stitches and needed to have them redone, so I keep the girls in an e-collar for the first few days, and if they are the type that try to scratch with rear feet (some do), a vet tech showed me a way of putting them in an old t-shirt (knotting it up around their belly) and covering the back feet in tube socks (no rubber bands around the feet--that's not safe). It looks awful, but better a few days looking like a GSD-Hausfrau than opening up stitches.
Here are the post-op instructions for the spay place a lot of rescues in my area use - it says keep them as calm as possible for 7-10 days (which may differ from your own vet's instructions):
|I've always done on leash quiet walks as needed. No running, jumping, or Tom foolery just slow easy walking for short periods. I found it much preferable to having a stir crazy dog and haven't had any issues so far with complications
|My vet told me the same thing and although my girl went crazy, she got no walks for 3 weeks. Her incision did open a bit the first weekend so that's why she had to rest another week. It wasn't fun but I'd do what the vet recommended. If her incision opens, you'll be bummed you have to wait even longer.
Walking after being spayed?
Hi everyone, my girl just turned 6 months and was spayed yesterday. Everything went well and today she is acting 100% normal already. The instructions from the vet says no walking for 2 weeks until her stitches are removed but when I asked the tech about it she said walks are fine. I tried not walking her today as I was worried about hurting her stitches but she goes insane without her walking and at 5pm I took her on a short 10 minute walk since even those help her. I figured her being so insane and wild in the house from not getting her walks would hurt her more than a short walk on mostly flat side walk. Is walking her really ok? Shes on a short leash healing and no running or off leash stuff.
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Massachusetts > Secretary Of State > Corporations Division > Nonprofit Corporations
Certificate Of Change Of Address Of Resident Agent - Massachusetts
|Certificate Of Change Of Address Of Resident Agent Form. This is a Massachusetts form and can be used in Nonprofit Corporations Corporations Division Secretary Of State .
|Get this form for FREE as a print-only pdf
Filing Fee: $10.00 IDENTIFICATION no. ____________________ The Commonwealth of Massachusetts William Francis Galvin Secretary of the Commonwealth One Ashburton Place, Room 1717, Boston, Massachusetts 02108-1512 CERTIFICATE OF CHANGE OF ADDRESS OF RESIDENT AGENT (General Laws, Chapter 180, Section 10C) I, _____________________________________________________________________________________________ , Resident Agent (Exact name of resident agent) of _________________________________________________________________________________________________________ , (Exact name of corporation) having a principal office at ______________________________________________________________________________________ , (Street address of corporation in Massachusetts) certify that my business address has been changed to: ___________________________________________________________________________________________________________ . (Business address of resident agent in Massachusetts, including number, street, city or town and zip code) SIGNED UNDER THE PENALTIES OF PERJURY, this __________ day of________________________________ , 20 ___________, ______________________________________________________________________________________________ , Resident Agent. Note: By law, this certificate must be filed within five (5) days of such change of address. American LegalNet, Inc. www.FormsWorkFlow.com 180ccara 11/7/13 THE COMMONWEALTH OF MASSACHUSETTS CERTIFICATE OF CHANGE OF ADDRESS OF RESIDENT AGENT (General Laws, Chapter 180, Section 10C) I hereby approve the within Certificate of Change of Address of Resident Agent and, the filing fee in the amount of $ _______________ having been paid, said certificate is deemed to have been filed with me this ____________ d a y of ____________________ , 20 _______. WILLIAM FRANCIS GALVIN Secretary of the Commonwealth TO BE FILLED IN BY CORPORATION Contact information: _________________________________________________________ _________________________________________________________ _________________________________________________________ Telephone: _________________________________________________ Email: __________________________________________________________ A copy this filing will be available on-line at www.state.ma.us/sec/cor once the document is filed. American LegalNet, Inc. www.FormsWorkFlow.com


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Hello, Greetings from Seoul, Korea! I love reading books, listening to music, playing chess/piano, and writing. Harry Potter rules!!!
|< 1 2 3 4 5 6 7 8 9 10 11 12 13>|
: The Chronicles Of The Dark Lord, Part I by She Who Must Not Be Named
The Chronicles Of The Dark Lord, By Miss Hermione Granger...And with the Second Rising of the Dark Lord so began the final years of the Boy Who Lived, and it must be asked that had we done something different, had he not lost so much, would we have been able to change that which followed. And I myself must bear the burden of knowing that I too aided in his downfall, for I lost not only my friend, but also my hope to him.
Genres: Drama, Horror/Dark, Angst Era: Hogwarts Characters: Draco, Dumbledore, Ginny, Harry, Hermione, Neville, Ron, Snape, Voldemort
Advisory: Strong Language, Strong Violence, Sensitive Topic/Issue/Theme,
Published: 2004.02.25 Latest Chapter: 2004.05.08 Updated: 2006.05.05 Status: COMPLETED (59016 words)
: Harry Potter and the Wizard's Debt by RavenGryffendor
Set in Harry's sixth year. He deals with Sirius death, more characters become actively involved in his life, a few new secrets revealed, an enemy becomes unwanted but potentially necessary ally, and more. my first fanfic...we'll see how it goes.
Genres: Romance, Action/Adventure, Angst Era: Hogwarts Characters: Cho, Draco, Dumbledore, Ginny, Harry, Hermione, Lupin, Ron, Sirius, Snape Pairings: Harry/Cho
Advisory: Mild Language, Mild Violence
Published: 2004.01.06 Latest Chapter: 2004.04.08 Updated: 2005.09.14 Status: COMPLETED (121991 words)
: Harry Potter and the Silent Siege by swishandflick
Lord Voldemort has finally found a way to break Dumbledore's old magic and appears to kill Harry when his Death Eaters attack Privet Drive. For the Dark Lord, however, Harry's easy death seems almost regrettable for if he had not succeeded his next intricate plan would have proved "even more pleasurable to spring," a plan that would have involved Ginny Weasley's destiny with the Boy Who Lived and her own haunted past. R/H, H/G.
Genres: Romance, Action/Adventure Era: Hogwarts Characters: Draco, Dumbledore, Ginny, Harry, Hermione, Luna, Neville, Ron, Snape, Voldemort Pairings: Harry/Ginny, Ron/Hermione, Neville/Luna
Advisory: Mild Violence
Published: 2003.12.21 Latest Chapter: 2004.04.08 Updated: 2005.04.03 Status: COMPLETED (229476 words)
: Living inside Yesterday by Potter47
They say the truth will set you free...but do you want to be? They say that memories are the diary we all carry about with us...what a coincidence. They say that time flies...but in which direction?
Part I of the Yesterday Sequence. COMPLETE!
Genres: Romance, AU Characters: Ginny, Harry Pairings: Harry/Ginny
Advisory: Mild Language,
Published: 2004.01.04 Latest Chapter: 2004.04.07 Updated: 2004.04.07 Status: COMPLETED (79772 words)
: Changed By Staff by demongurl
Based on the movie Heartbreakers. LIly Evans and Cara Kurtis are almost Partners in crime, Cara marries the man, Lily gets him to cheat on Cara and they both cheat him out of his money, leave. While scamming their latest victim, things go wrong for Lily when she bumps into some people she hasn't seen for almost four years.....Finished at last, please read and review, tell me what you think
Genres: Romance Characters: James, Lily Pairings: James/Lily
Advisory: No Warnings
Published: 2004.02.18 Latest Chapter: 2004.04.04 Updated: 2005.10.22 Status: COMPLETED (25343 words)
: The Year Everything Changed by lilperuvybabi
It has everything from love, lust, practical jokes, and friendship.
Genres: Romance, Humor Characters: James Pairings: James/Lily
Advisory: No Warnings
Published: 2003.12.17 Latest Chapter: 2004.03.31 Updated: 2005.07.06 Status: WIP (152506 words)
: Harry Potter and the Rise of the Dark Lord by LogicalRaven
Continuation to Harry Potter and the Perils of the Unknown. This year Harry is going to make a choice. A choice that will affect the rest of his life. Set in his seventh year.
Genres: General, Romance, Action/Adventure Era: Hogwarts Characters: Draco, Dumbledore, Ginny, Harry, Hermione, Lupin, OC , Ron Pairings: Harry/Cho, Ron/Hermione, Other Pairing
Advisory: Mild Language, Mild Violence
Published: 2003.12.04 Latest Chapter: 2004.02.28 Updated: 2004.02.28 Status: COMPLETED (129874 words)
: The Warmth by Alisha0715
Summary: Draco Malfoy and Hermione Granger were in an intense relationship, but when Hermione grew to fear him instead of love him, she split up with him. Draco would do anything to get her back, but what happens when his jealousy, anger, and love get in the way? Slightly AU.
Genres: Romance, General, Angst Characters: Draco, Hermione Pairings: Draco/Hermione
Advisory: Strong Language, Scenes of a Sexual Nature, Scenes of a Mild Sexual Nature
Published: 2004.01.25 Latest Chapter: 2004.02.27 Updated: 2004.02.27 Status: COMPLETED (90979 words)
: Harry Potter and the Web of Prophecies by SarahLupin
*Written pre-HBP and now AU* Takes place directly after OotP ends. Harry is still mourning the death that has changed his life. When he hears about a second death, discovers that Voldemort is following him, finds out about his past , discovers another prophecy, along with Remus Lupin's long-lost love, what will happen? Remus/OC, Ron/Hermione, Harry/OC Read/review please!!!
Genres: Romance, Action, General, Angst Characters: Draco, Dumbledore, Ginny, Harry, Hermione, James, Lily, Neville, OC, Remus Lupin, Ron, Sirius Black, Snape
Advisory: No Warnings
Published: 2003.09.24 Latest Chapter: 2003.12.06 Updated: 2006.03.04 Status: COMPLETED (68938 words)
: Harry Potter and the Perils of the Unknown by LogicalRaven
Warning OotP Spoilers. Harry starts his sixth year at Hogwarts, but he's in for some surprises. He's going to learn the true story of his parents, and learn to deal with loss. There might be a little romance and adventure.
Genres: General, Romance, Angst Era: Hogwarts Characters: Cho, Dumbledore, Ginny, Harry, Hermione, Lupin, OC, Ron, Snape Pairings: Harry/Cho, Ron/Hermione, Other Pairing
Advisory: Mild Language, Mild Violence
Published: 2003.09.14 Latest Chapter: 2003.12.03 Updated: 2004.03.27 Status: COMPLETED (115622 words)


text:
we both made our own prom dress!
I'm not sure if you have heard of the scholarship you can get if you make your prom suit/dress entirely out of duck tape. When I first thought about it, I thought of a crappy grey jacket. But after going on the website, I am truly stunned!
After prom party at hilton hotel, such a nice room! at 3am we went out to mcd drive thru and there were 3 guys standing by the drive through menu, we asked them what they're doing and one of them was holding a flyer and a permanent marker, "I'm writing down my orders" except in Chinese. Turns out they're from Vancouver, around 30 years old and smoking out of a pipe. I couldn't help but crack up, we ended up ordering for them and in return they gave my bf some random old style cigarette!
The next day, ate breakfast at Sunset Grill and met up with everyone before heading to wasaga. SUCH a delicious all day breakfast place! yummm.
how was your prom day?


text:
Southeast Transportation Study (SETS)
Keeping Seattle Moving
SDOT would like to thank all those who worked with us to shape the Southeast Transportation Study (SETS). SETS will help guide public and private transportation investments in Southeast Seattle through 2030 to provide greater safety, mobility, and access for all modes of travel.
SETS contains 72 project recommendations estimated to cost $67 million. SETS established priorities and, as project recommendations in this report move towards implementation, SDOT will again reach out to affected neighborhoods to provide information and secure their input.
Download the full report here.
The Southeast Transportation Study (SETS) builds on existing planning to provide a comprehensive, transportation plan for the area. It will serve as a blueprint for financing and programming transportation improvements in Southeast Seattle over the next two decades.
The study's goals are to:
Get Involved
For more information, please contact Tony Mazzella, SDOT Project Manager, firstname.lastname@example.com, telephone 206.684.0811.
March 28th Agenda


text:
If you have product information to contribute to our community, join the forum for free and post up!
You can interact with other users of your product and trade tips and advice on its use.
Ask someone in our forums for help!
Do-It-Yourself Product Repair Forum
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someone else.
We encourage all product guru's to help others here.
List Links To Your User Manuals
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that you need. We have a wide selection of
manuals and important documentation and will be locating more each week. So be sure to keep us in mind when you need
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to the site you can trust!
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text:
SigmaScan Pro 5.0
Related Software Categories: Applications | Business Finance | Database Management | E-mail | Inventory Systems | Legal | Market-Tracking Tools | More Business... | MS Office | Other
Sigma Scan Pro automated image analysis program provides you with image solutions for your scientific image collections with its powerful suite of image analysis tools which will count, measure and analyze images from any TWAIN supported device. The program provides more than 50 measurement options for converting your images into analytical data and its built-in algorithms will allow you to count and number up to 64,000 image objects and collect the data in a spreadsheet. Using the program for biological science purposes, you can quickly count and measure organisms or cells and apply automation to your growth studies and the program can also enable you to measure particle sizes and shapes from your microscopic slides or micro graphs. Overlay planes featured in Sigma Scan Pro can be used to produce a count and distribution of bacterial colonies on an agar plate. For your astrophysical images in physics or astronomy, the program will turn your images into qualitative data and enable you to prepare descriptive presentations. You will be also provided with color look up tables that can be applied to grayscale images for highlighting image features to aid you in the diagnostics of your field if your field is in Medical Research. Whether you're investigating coral coverage and diversity, studying the distribution of oil droplets, and Engineer requiring circuit board design analysis from an image, or you need to determine the distances and highlight specific areas of your satellite photography, Sigma Scan Pro program will meet your requirements.
System requirements: Not specified
Price: $1,499.00
SigmaScan Pro 5.0 user reviews
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Pinterest's dramatic rise as the visual social media mecca for content makes it a critical component of your 2013 social media and content marketing plans.
Pinterest has gathered force in terms of numbers. From a top-line perspective, it attracts over 20 million unique visitors a month who spend almost 16 minutes on the site per visit yielding 1.5 billion page views per month, based on Fast Company's infographic. If that doesn't convince you, Pinterest is the fourth largest source of traffic, according to Shareaholic.
Here's a five-step strategy to get your Pinterest presence on track to yield measurable results. When you implement these actionable tactics, make sure you follow Pinterest etiquette.
Set Marketing Objectives for Your Pinterest Activity
Your Pinterest goals must be specific and measurable. Here are five options.
- Attract traffic. Leverage Pinterest to drive traffic to your website or blog.
- Present your brand visually. While many businesses, offerings, and brands aren't instinctively visual, Pinterest forces marketers to translate their brand into graphic format. SEOmoz does a great job.
- Build your brand. Like other forms of social media, Pinterest enhances your brand by leveraging the visual strength of your 360-degree brand through images, hashtags, and descriptions.
- Support community. Using Pinterest to create a conversation around relevant topics enables businesses to build community, recommends Beth Hayden, author of "Pinfluence: The Complete Guide to Marketing Your Business With Pinterest." To understand how to do this for your organization, Hayden pointed to the Pinterest presence PediaStaff, a national staffing firm that recruits and places pediatric therapists, has developed. With two distinct target audiences – the therapists it places, and the schools, hospitals, and clinics for which it provides therapists – PediaStaff runs ongoing discussions through its boards.
- Drive sales. Visitors are 10 percent more likely to purchase than visitors who arrive from other sites, according to Tamba's infographic.
Know your Pinterest Audience
Define your target market on Pinterest through the use of a marketing persona and a social media persona. Further, don't assume that it's a female-only online scrapbook site. The male-female mix is changing as men are increasingly joining the site, although the ratio is still predominately female.
Show Your 360-Degree Brand on Pinterest
Like any social media site, you must extend your brand to take advantage of the social media platform's strengths. In addition to the use of your 360-degree brand, here are three brand elements to include.
- Optimize your Pinterest profile settings. Here's another tip from Pinterest expert Beth Hayden. Check that your business name is on your Pinterest home page. Complete your firm's information with optimized keywords. Also, link your Pinterest profile to your website and other social media outposts.
- Create targeted pinboards. Use your pinboards to reflect different aspects of your brand.
- Develop brand by association. Consider how the pins you curate relate to your brand. Examine their target audience and how they're regarded.
Create a Pinterest Content Marketing Strategy
Pinterest content is visual in nature and draws on the exponential growth of shared images on social media. On Pinterest, there are two major forms of content: original content and curated content, including repins. Regardless of which approach you use, ensure that each image maximizes results.
- Incorporate compelling images into every piece of content you publish. Before you create the graphic element, make it appealing and share-worthy for your target audience. Think like a magazine editor to condense your story into an image. Here are five tips to help you extend your use of images.
- Curate other people's content. As with other social media venues, it's bad form to just pin your own content. Therefore to stand out, actively seek interesting and visually alluring content that satisfies your Pinterest followers' needs. While 80 percent of Pinterest content is repins, only following a repin strategy doesn't enhance your image as an expert.
Measure Pinterest Results
Track your Pinterest results back to your key objectives for the platform. Start by counting the number of pins from your website, the number of repins your content receives, and the number of followers you get on your overall Pinterest account and on individual pinboards. This'll provide insight into how Pinterest supports your marketing objectives.
Since Pinterest is becoming a top social media venue, at least stake out your organization's position and build the foundation for future growth, especially given how strong images are in today's marketing mix. These five tactics provide the basis for a Pinterest strategy.
Do you have a Pinterest strategy in place? If so, what have your key learnings been? What have the major stumbling blocks been?
Happy marketing,
Heidi Cohen
Pinterest image via http://www.softicons.com/free-icons/system-icons/windows-8-metro-invert-icons-by-dakirby309/pinterest-alt-icon.
This column was originally published on Oct. 1, 2012.
Related reading
Influencing the customer journey is just as important as understanding it
For years, marketers have scrutinized every aspect of the customer journey--but it is becoming increasingly apparent that just understanding it isn't enough. Here's how technology is enabling marketers to go from understanding to influencing their customers' journeys.
Five ways to maintain data quality in your analytics
A data-driven strategy is an essential part of any marketing role, making data quality a top priority for senior marketers. But how can you ensure your data is clean and accurate?
How to measure the ROI of social media campaigns
What's the best way to measure Return on Investment when planning social media campaigns? How can you justify the time and the budget spent on them?
The 4 key metrics to a successful email
Now that you've written your high-performing email, there's one last thing you need to do after you send it: measure how it performs. Unfortunately, not all metrics are made equal. Which is why it's important to know exactly which metrics to base your email performance assessment off of.


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There are over 12,200 children under the age of 5 living in Saginaw County. Brain research has shown us that by age 4, 85% of a child's brain is formed. Those first few years of life are pivotal in shaping a child's future!
The Saginaw Great Start Collaborative is a partnership of parents, community agencies, business leaders, educators, health care providers, faith and philanthropic leaders - all working together and committed to establishing and maintaining a comprehensive early childhood system that addresses all factors that have an impact on a child's readiness for school and life. A priority this year is to reduce infant mortality in our community.
The Annual Meeting PowerPoint details our accomplishments for the last fiscal year. Our local collaborative is part of a larger state-wide Great Start system.


text: Hello, I have a 1993 Fleetwood Brougham whose heater-A/C fan has a mind of its own. It turns on an off all by itself, if I have it turned on. I can wiggle the wires to the fan motor under the dash on the right side and sometimes it will turn on the fan. I've removed the plug and reduced the opening on the female plug and wired brushed the male part on the plug in the A/C unit. It still only works sometimes. I have folded some paper up and wedged it under the one side of the plug and that worked for a day or two. Has anyone had this problem before and what did you do to fix it. Thanks Don


text:
Schools & Colleges
A-Z Index | Find a Health Care Provider
Contact Us | Maps and Parking
Contact Info:
Faculty Advisor Julie Paranka, MD
Coordinator Steven Cruse
Academic Office 1, MSF49612631 E. 17th Ave.Aurora, CO 80045
Phone: 303.724.0975Fax: 303.724.0977
Family Medicine Interest Group (FMIG) is comprised of medical students interested or thinking about pursuing a career in Family Medicine. It is run by a student volunteer steering committee. This committee is responsible for planning all events with the support of personnel in the Family Medicine Medical Student Education office, including Steven Cruse, Program Coordinator and Julie Paranka, MD, FMIG advisor.
An important activity of the FMIG is the monthly Family Medicine lectures. These are noon-time talks open to the campus on various topics related to Family Medicine and Primary Care. Other activities sponsored by the FMIG are workshops on IVs, immunizations, casting and suturing.
For more information about FMIG, please visit the FMIG page on the new Medical Student Education website: FMStudentEd.org
© The Regents of the University of Colorado, a body corporate. All rights reserved.
Accredited by the Higher Learning Commission. All trademarks are registered property of the University. Used by permission only.


text:
once my initial mistake of placing the networks close
to my preamp has been corrected the slight buzz is gone;
now each small network is connected to each of the four IC's
at just 1 inch of each amp input
also, the initial impression of darkness has decreased
considerably, so i've to assume some breaking in has been
taking place with so minute resistors & caps
i believe the resolving power of my maggies is now
increased about 30%, and the consequences are clear in
every department: more low level detail & ambience, no more
brightness (even when listening at deafening vol), much better
bass & dynamics, better, more cohesive imaging, etc, etc,
so in a word much more musicality
yesterday i was listening to particular orquestral recordings which
formerly were difficult to me: 1st act of Karajan's Die Walküre
(now Vicker's beautiful, big, very expressive voice no
longer does any harm to my ears), Hogwood's Bach's Orquestral
Suites (no longer unbearably bright and harsh), and Lindberg's
recent Aura (now perfectly listenable and enjoyable in all
its higly dense orquestral complexity & power)
summing up: vertical biamping with a well designed passive
line xover (thanks once again Davey!!) is able to allow
my 1.6 to offer even much more musical pleasure & emotion
next? to replace my present junk resistors & caps by much
better ones
best, paco
This post is made possible by the generous support of people like you and our sponsors:
Topic - 1.6 passive line xo update - paco 04:34:03 02/08/01 (11)
- addition on bass - paco 10:12:15 02/09/01 (2)
- Did you also notice an increase in "slam"? (nt) - MikeCh 10:17:32 02/09/01 (1)
- yes! e.g. percussion with more engaging, visceral impact (nt) - paco 10:21:46 02/09/01 (0)
- Re: 1.6 passive line xo update - MikeCh 11:23:57 02/08/01 (7)
- Re: 1.6 passive line xo update - paco 13:34:32 02/08/01 (6)
- Re: 1.6 passive line xo update - MikeCh 14:15:50 02/08/01 (5)
- Re: 1.6 passive line xo update - paco 17:35:29 02/08/01 (4)
- Re: 1.6 passive line xo update - MikeCh 10:14:18 02/09/01 (0)
- resistors - Arbelos 06:03:51 02/09/01 (2)
- now seriously... - paco 06:44:37 02/09/01 (0)
- hey Arbelos! why do you make me suffering so much? :-) (nt) - paco 06:16:29 02/09/01 (0)
You can not post to an archived thread.


text: Mountaineer Montessori offers camp sessions By Staff reports May 15, 2013 Story Share CHARLESTON, W.Va. -- Registration is now open for the "Best. Summer. Ever.," six-week series of unique experiential learning and camp sessions for children ages 3-12, offered by the Mountaineer Montessori School, 308 20th Street. A wide variety of specialty and theme-week programs, including geocaching in the Kanawha State Forest, drama classes with the Charleston Theatre Arts Workshop and "Amiguitos" Spanish activities will be offered in two separate but complementary camp programs. Faculty and camp leaders are subject-matter experts and highly experienced and professionally trained in both educational and camp settings for children.MMS Summer Program 2013, featuring focused exploration activities each week, will be held June 17 to Aug. 2. Full (9 a.m. to 3 p.m.) and half-day (9 a.m. to noon) sessions and after-camp (3 to 5:30 p.m.) programs will be offered. Learn to Swim classes at the University of Charleston are included for full-day campers. Registration is open to all children and is not limited to MMS students.Children may register for one or all of the following sessions:June 17-21: "Geocaching, Maps and Wilderness Exploration," for children ages 3-12 with Jessica Rodecker. (Geocaching is a high-tech treasure hunt using GPS to hide and seek containers, called "geocaches" or "caches."). Transportation will be provided from the school to the Kanawha State Forest.June 24-28: "Amiguitos" Spanish Camp for children ages 3-6 with Ana Wentz. July 8-12: "Around the World Magic Carpet Ride" for children ages 3-6 with Samantha Van De Berghe.July 15-Aug. 2: Drama with Charleston Theatre Arts Workshop with Jessica Rodecker.With the exception of week one, weekly registration is $215 for a full day and $120 for half-day sessions; the after camp plus program is $45 per week. A sibling discount is available. Registration for the geocaching session is $225. To register, go to www.MountaineerMontessori.org or call 304-342-7870. A second program, "Summer Fun Camp with Nancy and Sophia," is scheduled for June 24-July 26. Registration is open to rising first graders and older. Activities include: storytelling; swimming at UC; bike riding; cooking classes; natural arts and crafts; and Friday in the Kanawha State Forest. Leaders are Nancy Johnston, an MMS physical education and art instructor with more than 16 years of experience, and MMS alumna Sophia Kaufman, a certified lifeguard and former counselor at Camp Glenburn in New Brunswick, Canada."Summer Fun Camp" will run from 9 a.m. to 3 p.m., with early drop-off available for an additional fee. Registration is $200 per week, with a sibling discount offered. To register, contact Johnston at 304-344-0666, or email firstname.lastname@example.com. Story Share Story Share Trending Now 1 Balzout co-founder Scott Cable dies at 54 2 Overdose deaths in KY have hit unprecedented levels, officials say 3 After losing job to flood, man opens Mexican restaurant in Clendenin 4 Most Marshall students to pay 9 percent more 5 Hurricane's Aaron Perry comes to terms with Red Sox WVU names Foundation Scholars Previous Story Bulletin board: May 16, 2013 Next Story


text:
Originally Posted by acptulsa
Hat tip to Suzanimal for the following:
Originally Posted by The Daily Mail
Did a delay in response give the gunman more time? Cops face questions over why it took three hours for SWAT teams to storm Orlando nightclub as police chief admits officers may have shot some of the VICTIMS
...Police Chief John Mina has also admitted that some of the victims may have been hit by officers' gun fire.
However he insisted it is a part of the investigation into the horrific attack.
Originally Posted by acptulsa
I just can't decide who to vote for in the presidential race. They're both just so perfect! I can't believe it. Things are just going so well I never considered firing the president, but this Romney guy is just such a temptation!
Romney promises us more war. Obama promised us just the opposite, but that's ok, because he saw Dubya's two wars and raised us three police actions. I think that's a wonderful thing, and can't wait for the next one. I heard somewhere that with six you
Originally Posted by acptulsa
Once upon a time, there was a thing called the Interstate Commerce Commission. It was founded to prevent kamikaze capitalism amongst railroads in a day when their efficiencies and primitive technology pretty much guaranteed them a monopoly in viable transportation.
The best thing Reagan did, in my opinion, and the one time I felt some hope for a moment that he would prove to be the libertarian he claimed to be, was when he abolished this bureau. But it was a decade too late to save
Originally Posted by acptulsa
'What your daddy did to you was abuse.'
'How dare you talk that way about my daddy?!'
What has it to do with politics? Everything. Politicians piss us off, then try to misdirect our anger 'across the aisle' to people who are fundamentally exactly the same, but wear a different party label. The game is age old, but still works.
People are angry, but they are often in denial about it. They know they're angry, but they don't want to admit they're angry


text:
All Android applications categories
Published: 2013-10-25, by Manu Galvez.
Don't know how to start a lift conversation? 5001 Amazing Facts is going to help you with that. "Did you know that...?" is going to be your favorite phrase. Learn everyday one or more facts and improve your general knowledge just by taking a glance at your mobile device home screen.
Facts are written on cards you can slide. Start from the beginning or from the last slide or search facts by keywords. That's perfect if you want to learn some facts related to a specific topic. In addition, you can "favorite" those you like best and access them quickly from the favorites section. You can also share those facts with your friends via Facebook, Twitter, SMS and e-mail. In addition, there's a 4x1 home screen widget that displays one fact at a time.
The app is backed by a powerful concept: our need to learn interesting things. What's more, it brings that new knowledge in quick digestible pills. Just two catches should be mention: first, it would be great having more widget sizes and set its update frequency (or even manually slide facts from the widget); second, design should be enhanced, it's too sober.
Tags: 5001 amazing facts , amazing facts , 5001 amazing facts list , 5001amazingfacts , 5001 , 5001 amazing , amazing facts of 2011 , amazing facts of the world , amazing facts with comment
by Manu , Appszoom
Oct 25, 2013
from 216 reviews
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GAO Tells DOD To Reassess Length of EELV Block Buy
The Government Accountability Office (GAO) released a report today recommending that the Department of Defense (DOD) reconsider the number of years its block buy of Evolved Expendable Launch Vehicles (EELVs) will last. SpaceX, in particular, has expressed concern that if DOD commits to buying 40 EELVs over the next five years, it will effectively preclude the company from competing with its Falcon Heavy design because it is not clear that the government will need that many launches.
The GAO report comes on the heels of an announcement by NASA, the Air Force and the National Reconnaissance Office (NRO) last week that could create opportunities for emerging launch service suppliers like SpaceX. On Friday, the three agenices announced a coordinated certification process for commercial launch services, including "new entrants."
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text:
Welcome to E-Books Directory
This is a freely downloadable e-book.
Algebraic geometry and projective differential geometry
Read this book online or download it here for free
Custom Search
Algebraic geometry and projective differential geometry
by Joseph M. Landsberg
Publisher: arXiv 1998
Number of pages: 70
The author discusses: Homogeneous varieties, Topology and consequences Projective differential invariants, Varieties with degenerate Gauss images, When can a uniruled variety be smooth?, Dual varieties, Linear systems of bounded and constant rank, Secant and tangential varieties, Systems of quadrics with tangential defects, Recognizing uniruled varieties, Recognizing intersections of quadrics, Recognizing homogeneous spaces, Complete intersections.
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text:
George Jones Remembers Old Friends on New Project
He's the legendary hit maker often dubbed the greatest living country singer, and it's hard to find an artist of any genre who doesn't dream of collaborating with him. So when George Jones decided to record an album of duets, he called on some very lucky friends.
Jones' new CD, 'Burn Your Playhouse Down: The Unreleased Duets' features an eclectic mix of musicians ranging from Dolly Parton and Vince Gill to Mark Knopfler and Keith Richards, just to name a few. And an album of George Jones duets wouldn't be complete without his most famous singing partner, Tammy Wynette, who is featured on a 1977 recording that frames the CD with a duet with their daughter, Georgette.
The Boot caught up with the 77 year old legend, who just celebrated an illustrious 55 years in the recording industry. In this candid chat, Jones talks about new music, old friends and why he thinks today's country radio is more about looks than sound.
Seven songs on your new album were recorded during a star-studded recording session back in 1993. What made you decide to put together this collection 15 years later?
We did two songs with each artist, back when we did the 'Bradley Barn Sessions.' Well, we had an album in the can at the same time we did the other ones, so we decided to bring them out and update them. We decided to title it 'Burn your Playhouse Down,' which is the song that Keith Richards did with me. And incidentally, I thought he did a wonderful job playing country music! We recorded it during a terrible ice storm (in Tennessee). He flew in from California. I never dreamed that he could possibly make it.
'You Me and Time' is a duet with your daughter, Georgette, about some painful family memories. Was that a tough recording session, given the subject matter?
No, it was really wonderful. She wrote the song, and I thought it was sweet of her to write something about us, because we didn't get to communicate too often during the absence period of her growing up. I just thought it was a great idea.
Of all the songs you recorded with Tammy, do you have a favorite?
'Golden Ring' or 'We're Gonna Hold On' — We wrote that one together with Peanut Montgomery. We did a lot of ballads, too, that were just album songs.
'He Stopped Loving Her Today' is often referred to as the greatest country song of all time. Did you know how special it was when you first heard it?
[laughs] To be honest with you, I thought it was too sad. I took a copy of the tape with me and carried it with me almost a year before I recorded it. But it was on my mind everyday. So (my producer) Billy Sherrill said, 'Let's just go ahead and cut it anyhow.' And he bet me $100 that it would be a hit. And I said, 'Well I can't lose either way! But I don't think it will be a hit. It's too sad.' But how wrong can you be?
What's your feeling about the influx of pop artists crossing into country?
There are some fine artists out there, some good singers. The only thing I disagree with is that they don't still include some of the older artists. They play George Strait, which is great. I love his stuff. And Alan Jackson. But I don't understand why they play two artists that are pure country, traditional, but they won't play any other older artists. And the only thing that is tied to is good looks, I guess! [laughs] You've gotta be long and tall and have a cute little behind and all that stuff!
Do you ever miss the rebellious, outlaw days?
I remember the outlaw days very well. They wanted me to join in on that down in Texas. But I said, 'I've already been through that — growing a beard and all.' And I thought they were maybe trying to be hippies, too. So I didn't want to get into that. But it did work out great, especially for three of my favorite people — Willie Nelson, Waylon Jennings and Johnny Cash.
If Waylon and Johnny were alive today, and you and Willie took them out for a night on the town, what would we catch you doing?
Well, I'd be trying to keep up with 'em to start with! [laughs] Nah, I'd be right up there with 'em. We were all great friends, especially Waylon and Johnny. We went out and went to each other's homes a lot, and I sure do miss that.
'Burn Your Playhouse Down: The Unreleased Duets' Tracklist:
'You And Me And Time' (With Georgette Jones)
'The Window Up Above' (With Leon Russell)
'She Once Lived Here' (With Ricky Skaggs)
'Rockin' Years' (With Dolly Parton)
'Burn Your Playhouse Down' (With Keith Richards)
'Selfishness In Man' (With Vince Gill)
'Tavern Choir' (With Jim Lauderdale)
'I Always Get It Right With You' (With Shelby Lynne)
'When The Grass Grows Over Me' (With Mark Chesnutt)
'I Always Get Lucky With You' (With Mark Knopfler)
'You're Still On My Mind' (With Marty Stuart)
'Lovin' You, Lovin' Me' (With Tammy Wynette)


text:
Salem garden store to reopen with new name, family tie
Salem -In the greenhouses located just off Route 85, workers are putting the finishing touches on tables that will soon hold a broad selection of plants for sale.
The landscaping business that has operated here for nearly three decades will be opening again on March 23 under the name Burnett's Country Gardens.
The buildings and logo will look familiar to returning customers, but the owner is new. Todd Burnett, whose parents David and Cheryl first opened the garden center as Salem Country Gardens in 1983, bought the property in a foreclosure auction last year.
The Burnetts sold the company in 1998, and it went through a series of owners before it was foreclosed upon for non-payment of real estate taxes.
Working with the Burnett family "was and is the best time of my life," said Heather Thibeault, Todd Burnett's marketing coordinator. She was one of a "dream team" of David and Cheryl's employees that came back to work with their son.
"The Burnett family � when someone wants to work and is willing to learn, they encourage it," said Thibeault.
The younger Burnett, who remembers clearing the garden lot of rocks with his friends as a kid, doesn't plan to make any radical changes. But he does hope to put a "more modern spin" on the business.
The marketing strategy showcases the more contemporary feel: Burnett's Country Gardens is getting out the word about its opening through Facebook, Twitter, YouTube and Pinterest.
The company is also in the process of developing new features, such as a Saturday farmers' market and a customer loyalty program called Bloomy Bucks.
One of Burnett's priorities is to stock Burnett's Country Gardens with as many locally grown plants as possible. He will grow some on site and will carry perennials from Franklin and shrubs and trees from Lebanon.
One major supplier will be his own 85-acre farm in Canterbury, which distributes to wholesale customers in New England and New York.
Burnett, who earned a degree in ornamental horticulture from the University of Connecticut after learning hands-on from his parents, enjoys operating his wholesale farm but missed the interaction with retail customers.
"I love being outdoors and working with plants and people," he said. He grew up in Salem and purchased Burnett's Country Gardens because his "heritage is here."
There are only two weeks left until the opening day and Burnett still has a number of things to do before the site will be ready.
The blizzard in February almost caused the greenhouses to collapse, he said. He and his employees were able to save the structures, but they must replace the plastic they cut down in the process.
They will also need to finish setting up the new fixtures and computers systems, as well as bring in the inventory. Burnett said that he is still waiting for some deliveries.
Burnett will also need to decide what to do with the Habitat for Humanity ReStore area. That company, which sells used furniture and other items to benefit Habitat for Humanity, will be moving to a new location in May.
Thibeault recalls that the Burnetts always had something going on at Salem Country Gardens - in addition to inviting famous garden speakers, they held hay rides and brought in real reindeer one winter.
Their son is headed in the same direction. Burnett's Country Gardens has a full calendar of events, starting just a week after the store's soft opening.
The theme of the March 30 event is "A spring of new beginnings," and it will feature a scavenger hunt for children in lieu of the familiar Easter egg hunt.
The garden center will also play host to a number of baby animals for the day: goats, alpacas, bunnies, chicks and ducks will be visiting from local farms.
A grand opening is scheduled for just over a month later, the weekend of May 4 and 5. 97.7 FM WCTY, a Norwich-based country music station, will be doing a live radio show, and the garden center's vendors will be displaying their products throughout the property.
The Salem Fire Department will hold demonstrations of their fire trucks and will be sponsoring a lunch fundraiser for a local girl with leukemia. The Salem Cub Scouts will also be holding a lunch to raise money for their pack.
The garden center is "big on promoting other small businesses" and developing a relationship with them, said Thibeault, and their events were designed with this in mind.
On Mother's Day, a busy day for the garden center, they will partner with the Jewett City company Extreme Cakes by Heather to offer mini-cupcakes alongside their flowers.
Thibeault described Extreme Cakes by Heather's products as "beautiful, beautiful stuff," and hopes to offer one-stop Mother's Day shopping to "make people more comfortable."
The day before Father's Day, a representative from Maple Brook Forge in Coventry will be on hand to sharpen knives and tools.
Events, workshops and seminars will be announced on Burnett's Country Gardens' website, burnettscg.com, which will launch soon.
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