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Preferred Apartment Communities, Inc. Announces Acquisition
ATLANTA, April 29, 2011 /PRNewswire/ -- Preferred Apartment Communities, Inc. (NYSE AMEX: APTS) ("PAC") today announced its acquisition of Oxford Trail Apartments, an existing multifamily apartment community located in Hampton, Virginia. Oxford Trail was completed in 2006 and consists of 204 apartment homes, with a current occupancy of approximately 98%. PAC will rename the property "Trail Creek" and brand it as "a Preferred Apartment Community." PAC acquired Oxford Trail for a purchase price of $23.5 million through a loan originated by Jones Lang LaSalle Operations, L.L.C., and expects the loan to be transferred to Freddie Mac within 60 days. The non-recourse financing bears a floating interest rate of 280 basis points above the 30-day LIBOR, capped at 6.85% per annum, and matures in May 2018. There are no loan guaranties provided by PAC. About Preferred Apartment Communities, Inc.Preferred Apartment Communities, Inc. is a Maryland corporation formed to acquire multifamily properties in select targeted markets throughout the United States. As a secondary strategy, we may acquire senior mortgage loans, subordinate loans or mezzanine debt secured by interests in multifamily properties, membership or partnership interests in multifamily properties and other multifamily related assets. PAC intends to elect and qualify as a real estate investment trust for U.S. federal income tax purposes, commencing with our tax year ending December 31, 2011. Forward-Looking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. As a general matter, forward-looking statements reflect our current expectations and projections relating to our financial condition, results of operations, plans, objectives, future performance and business. These statements may be identified by the use of forward-looking terminology such as "may", "will", "expects", "plans", "estimates", "anticipates", "projects", "intends", "believes", "outlook" and similar expressions. The forward-looking statements contained in this press release are based upon our historical performance, current plans, estimates, expectations and other factors we believe are appropriate under the circumstances. The inclusion of this forward-looking information is inherently subject to risks and uncertainties, many of which cannot be predicted with accuracy and some of which might not even be anticipated. Future events and actual results, financial and otherwise, may differ materially from the results discussed in the forward-looking statements. Statements regarding the following subjects, among others, may be forward-looking: Our business and investment strategy; our projected operating results; availability of qualified personnel; local and national market conditions and trends in our industry; demand for and lease-up of apartment homes, supply of competitive housing products, and other economic conditions; availability of debt and/or equity financing and availability on favorable terms; changes in our asset values; our ability to maintain our qualification as a REIT for U.S. federal income tax purposes; estimates relating to our ability to make distributions to our stockholders in the future; and economic trends and economic recoveries. Additional discussions of risks and uncertainties appear in our filings with the Securities and Exchange Commission, including our final prospectus filed with the Securities and Exchange Commission, under the heading "Risk Factors". All information in this release is as of April 29, 2011. PAC does not undertake a duty to update forward-looking statements, including its projected operating results. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. PAC may, in its discretion, provide information in future public announcements regarding its outlook that may be of interest to the investment community. THIS IS NEITHER AN OFFER TO SELL NOR AN OFFER TO BUY ANY SECURITIES OF PREFERRED APARTMENT COMMUNITIES, INC. ANY SUCH OFFERING MAY ONLY BE MADE BY MEANS OF A WRITTEN PROSPECTUS. THERE SHALL BE NO SALE OF THESE SECURITIES IN ANY STATE OR JURISDICTION IN WHICH SUCH AN OFFER, SOLICITATION OR SALE WOULD BE UNLAWFUL PRIOR TO REGISTRATION OR QUALIFICATION UNDER THE SECURITIES LAWS OF ANY SUCH STATE OR JURISDICTION. For further information about Preferred Apartment Communities, you may visit our website at www.pacapts.com. SOURCE Preferred Apartment Communities, Inc.
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Date: Tuesday, April 7th
Time: 7:00 PM
Place: First Presbyterian Church, 271 N. Walton Street
HTNA will host their Richardson Mayoral Candidate forum on April 7th at 6 PM. Invited candidates are: Place 1 - Rick Wilder running against incumbent Bob Townsend and for Place 4 - Claudia Tatum running against Mabel Simpson. All Highland Terrace residents and Mark Twain residents are invited.
Your neighborhood association needs your support! The board works hard to make you aware of all happenings in our neighborhood. Neighbors who pay the $15 membership dues help us provide activities and newsletters. We beautify the entrances by planting flowers and are working to acquire Highland Terrace street sign toppers. You may have noticed new townhouses at Brick Row rather than more apartments, which was accomplished with help from the HTNA. We have an active Crime Watch, which keeps everyone alert to crime & safety in our neighborhood. Our civic chair attends the City Council meetings and keeps us up-to-date on city activities. The HTNA also holds an annual picnic each fall, which is fun, and a great way to meet your neighbors. Pay your dues now and support our great neighborhood and HTNA. Please see the back page of this newsletter for a membership form.
The City of Richardson implemented Stage 3 Winter Water Restrictions Friday, November 1, 2013. The modification follows guidance by the North Texas Municipal Water District (NTMWD) which is facing critical shortages in its water supply due to below average rainfall, declining water levels of NTMWD reservoirs and the ongoing prohibition of pumping water from Lake Texoma due to a zebra mussel infestation.
Richardson Today Online is a monthly publication of the City of Richardson. It is free for Richardson residents. The publication is designed to keep citizens of Richardson informed of activities and news that may be of interest to them.
April 29, 2016 Here is the latest edition of Week In Review - a series of weekly messages from the Mayor and City Council to help Richardson residents and businesses keep...
April 22, 2016 Here is the latest edition of Week In Review - a series of weekly messages from the Mayor and City Council to help Richardson residents and businesses keep...

subset: commoncrawl


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5 Charts Showing a Year-End Stock Bounce
(GS - Get Report) is a good example of a downside setup right now.Goldman has turned out strong performance in 2012, rallying more than 30% since January while the broad market has only earned around a third of that. But a head and shoulders top in shares points to a decline in shares. The head and shoulders is a pattern that indicates exhaustion among buyers -- it's formed by two swing highs that top out at around the same level (the shoulders), that are separated by a higher high (the head). A breakdown below the neckline is the sell (or short) signal for GS. Momentum is adding some extra confirmation to this setup too. Fourteen-day RSI had been in an uptrend along with price, but the RSI uptrend broke back when the left shoulder was formed, and it's been trending lower ever since. Extra confirmation is just that, though -- wait for price to move below the $113 neckline before selling.Goldman Sachs I said earlier that not all of the trades we're looking at are bullish -- Goldman Sachs
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text:
New arrivals - latest additions to our list
Wines by grower - alphabetical
Languedoc Red Wine (AOC/AOP)
Languedoc Red Wine (IGP/VdP/VdT)
Languedoc White Wine
Roussillon Red Wine
Roussillon White Wine
South-West France Red Wine
South-West France White Wine
Provence Red Wine
Provence White Wine
Southern Rhone Red Wine
Southern Rhone White Wine
Burgundy Red Wine
Burgundy White Wine
Loire Red Wine
Loire White Wine
Rosé Wine
Sparkling and Sweet wines
Mixed Case offers
Vinaigrier - make vinegar from wine!
Olive Oil
Wine books
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Online Wine Shop
Burgundy Red Wine
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Maison Guillot-Broux Mâcon-Pierreclos 2012
Guillot-Broux Macon-Pierreclos
Pierreclos, Mâconnais, southern Burgundy
Medium-bodied red, aged 11 months in older oak barrels
100% Gamay
Alcohol (a.b.v)
Salads, cold cuts, pasta, seared tuna
Next day
Even better
Lovely now, but will age for 5 to 8 years
The translucent ruby colour and tremendously fragrant nose of this Gamay scores very highly on the come-hither scale. Cherry and redcurrant aromas abound, with subtle hints of spiced rhubarb, violets, new leather and damp earth, and perhaps a suggestion of fresh root ginger. The palate is delightfully fresh and invigorating, with a mouth-watering core of citrussy acidity and just the right amount of tannic grip to accompany the vibrant, tangy, spicy red fruit. Whilst superficially light and airy, it doesn't take too much scratching beneath the surface to reveal extra layers of complexity and flavour, which raise it to another level. It may be Gamay, but it is quite different to Beaujolais. Rather, it has a grace and elegance one might normally encounter in a light, vibrant young Pinot. A wonderful expression of the Gamay grape.
(Including: VAT at 20%)
Domaine Guillot-Broux La Myotte 2012 Bourgogne
Guillot-Broux La Myotte
Cruzille-en-Mâconnais, southern Burgundy
Medium-bodied red, aged up to 18 months in oak barrels
100% Pinot Noir
Alcohol (a.b.v)
Red meats and cheeses
Next day
Even better
Lovely now, but will age for 10+ years
The estate's top red, from an old, low-yielding vineyard on a mix of marl and limestone, comprising just 0.65 of a hectare, which was re-planted in 1956, with cuttings from Pinot Noir vines from the Cote de Beaune. With a planting density of 8,000 vines per hectare, the average yield is just 30 hl/ha - or just over half a bottle per vine!
A beautiful, bright, translucent cherry/carmine red colour, with a complex, perfumed nose, combining red summer fruits, white pepper and spice, with subtle woody and earthy notes. A good swirl and a few minutes' air reveals yet more complexity, with hints of redcurrant, old leather and woodsmoke. If it sounds elegant, that's because it is - and the palate certainly lives up to the promise of the nose, caressing the tongue with waves of tangy cherry and redcurrant fruit nuances, not to mention something almost floral, like violets and fruit blossom, with a hint of fine white pepper for good measure. It simply exudes elegance, in an almost feminine way, embracing rather than squeezing, as do the tannins, which are fine and gently grippy, whilst the most gloriously juicy acidity carries the flavours all the way through to a long, lingering finish. At the risk of labouring the point, this really is *proper* red Burgundy. Is it worth 24 quid? Definitely.
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Leon Stolarski says "drink less, but drink better!" Please consume alcohol in moderation.


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Number: 0562
Aetna considers measurement of serum or urinary collagen crosslinks or other biochemical markers of bone remodeling experimental and investigational for the screening, diagnosis, or management of osteoporosis because the clinical value of these markers has not been established.
Aetna considers measurement of collagen crosslinks experimental and investigational for screening, diagnosis, or management of bisphosphonate-induced jaw osteonecrosis, chronic kidney disease, osteogenesis imperfecta, or other indications because its clinical value has not been established.
Aetna considers measurements of cobalamins, osteocalcin, sclerostin, and plasma homocysteine for evaluating fracture risk experimental and investigational because their clinical value for this indication has not been established.
Aetna considers measurement of biochemical markers of bone remodeling for diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty experimental and investigational because the effectiveness of this approach has not been established.
Bone strength is affected by its mass, microarchitecture, macrogeometry, and rate of turnover. Bone remodeling can be assessed by the measurement of surrogate markers of bone turnover in the blood or urine. Markers of bone formation include bone-specific alkaline phosphatase, osteocalcin (bone Gla-protein), and procollagen I carboxy (PICP) and N-terminal (PINP) extension peptides. Markers of bone resorption include urinary levels of pyridinolines (Pyr or Pyralink) and deoxypyridinolines (D-Pyr or Pyrilink-D) and serum and urine levels of type I collagen telopeptides (C-telopeptide products (CTX) and N-telopeptide to helix (NTX)). The level of these markers may identify changes in bone remodeling within a relatively short time interval (several days to months) before changes in bone mineral density can be detected.
Guidelines from the North American Menopause Society (2010) state that "[t]he routine use of biochemical markers of bone turnover in clinical practice is not generally recommended." The guidelines explain that bone turnover markers vary from day to day, are affected by food intake and time of day, and lack assay standardization, limiting their clinical utility. Although some clinicians have found that biochemical markers can encourage adherence to therapy, several trials have found no difference in adherence when marker values are communicated to women.
An National Institutes of Health consensus conference concluded that although these biochemical markers of bone turnover may be useful as a research tool, their clinical utility has not been defined: "[A]ccording to available data, marker levels do not predict bone mass or fracture risk and are only weakly associated with changes in bone mass. Therefore, they are of limited utility in the clinical evaluation of individual patients" (NIH, 2000).
A systemic review of the evidence from the National Osteoporosis Foundation stated that, although biochemical markers of bone remodeling appear promising, these tests vary in sensitivity and specificity and "their appropriate role in patient management is not yet known." A guideline from the National Osteoporosis Foundation (2003) stated that although biochemical markers have been used to assess risk of fracture, assess bone loss, or monitor response to antiresorptive therapy, "biochemical marker tests cannot replace BMD testing." A National Osteoporosis Foundation clinician's guide to the prevention and treatment of osteoporosis (2008) states that "[b]iochemical markers of bone remodeling (resorption and formation) can be measured in the serum and urine in untreated patients to assess risk of fracture," and that "they may predict bone loss" and "may be predictive of fracture risk reduction." The clinician's guide indicates that although biochemical markers of bone turnover may be predictive of greater mean bone mineral density (BMD) responses when evaluating large groups of patients in clinical trials, the "precision error" of the specific biochemical marker, along with daily and seasonal variability in bone turnover, must be taken into account when evaluating individuals. Thus, "because of the high degree of biological and analytical variability in measurement of biochemical markers, changes in individuals must be large in order to be clinically meaningful".
An evidence review for the U.S. Preventive Services Task Force osteoporosis screening guidelines (2002) stated that biochemical markers of bone turnover for osteoporosis screening is "under investigation."
An Agency for Healthcare Research and Quality (AHRQ) technology assessment of diagnosis and monitoring of osteoporosis in women (Nelson et al, 2001) concluded that "[n]o single [biochemical] marker or cluster of markers accurately identified individuals who had osteoporosis, as determined by the results of densitometry. It is not surprising that agreement between the two tests was poor. Densitometry measures current bone status, whereas markers measure the process of bone turnover." The AHRQ assessment concluded that the value of biochemical markers in predicting fracture risk has not been established. "No marker was associated with increased fracture risk consistently across all studies. One study provides evidence that using markers in conjunction with densitometry may increase predictability, but this result has not been otherwise confirmed." The AHRQ found that biochemical markers have not been shown to help select patients for treatment. "Studies correlating marker results and bone loss indicated no clear trend. Furthermore, sensitivity and specificity of markers were too low to be useful for the purpose of selecting patients for treatment." The AHRQ also found that biochemical markers have not been proven to be useful in predicting a patient's response to therapy. "There is a small correlation between response to therapy as measured by densitometry and marker results, but no marker is accurate enough to reliably identify those individuals who will fail to respond to treatment." In addition, there are no prospective data showing improved clinical management of patients with other disorders affecting bone resorption and formation (e.g., primary hyperparathyroidism, hyperthyroidism, Paget's disease of the bone, rheumatoid arthritis, renal osteodystrophy, hypogonadism, steroid-induced osteoporosis, etc.) by quantification of collagen crosslinks.
Seibel (2003) noted that the clinical use of bone remodeling markers in individual patients poses considerable problems which so far have not been sufficiently addressed. Consequently, no scientific or clinical consensus exists as to the use of bone markers in the follow-up of patients with osteoporosis. Cefalu (2004) stated that although data are beginning to accrue suggesting that changes in bone turnover markers may be an accurate predictor of fracture risk reduction, further research is necessary to elucidate the link between changes in bone turnover markers and bone architecture as a measure of osteoporosis treatment efficacy. In a review on the clinical use of serum and urine bone markers in the management of osteoporosis, Srivastava, et al (2005) stated that several clinical studies have established the potential utility of markers to identify patients with rapid bone loss, to aid in therapeutic decision-making, and to monitor therapeutic effectiveness of various treatments. They also noted that elevated marker levels have been demonstrated to be associated with increased risk of fracture in elderly women, but their utility in predicting fracture is not yet established.
Recent evidence demonstrates that bisphosphonates increases bone mineral density (BMD) in the vast majority of patients, so that routine monitoring after initiation of bisphosphonates is not be warranted. Investigators performed a secondary analysis of data from the Fracture Intervention Trial using a mixed model to evaluate whether alendronate treatment had a fixed effect (i.e., similar for all patients) and, therefore, should not require monitoring, or random effects (i.e., different between individuals) (Bell et al, 2009). After 3 years, hip BMD increased by a mean of 0.030 g/cm2 in the alendronate group and decreased by a mean of a 0.012 g/cm2 in the placebo group. Most women in the alendronate group (97.5 %) experienced benefit (i.e., BMD increases 0.019 g/cm2). Considerable variation in BMD over time among treated patients existed, but this difference was less than the variation within individual patients; furthermore, absolute variation was small. Baseline BMD, age, body mass index (BMI), or general health did not modify treatment effects. The investigators concluded that "monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading." A commentary on this study (Biggs, 2009) noted that "these results strongly suggest that monitoring BMD after initiation of bisphosphonates is unnecessary. Ascertaining clinically relevant responses to bisphosphonates is difficult because of variability among patients. In addition, the beneficial effects of bisphosphonates might extend beyond their ability to increase BMD: Patients in the alendronate group whose BMD did not increase still had lower risk for fragility fractures." An editorialist (Compston, 2009) stated that "[t]he final nail in the coffin for monitoring bone mineral density is the observation that only a small proportion of reduction in fractures attributable to treatment is explained by a change in bone mineral density. For example, only 16 % and 4 % of the decrease in the risk of fracture associated with treatment with alendronate or raloxifene, respectively, is attributable to an increase in bone mineral density. Furthermore, some studies have found similar reductions in fracture regardless of whether bone mineral density increased or decreased on treatment." The editorialist also noted that there is no evidence that monitoring improves treatment compliance. "Because adherence with treatment for osteoporosis is poor, it could be argued that monitoring bone mineral density is justified because it should improve adherence and thereby maximise efficacy. We have no evidence to support this, however, and it would be difficult to identify people who do not adhere with this test because of the large measurement variability. Because non-adherence occurs mostly within the first three months of starting treatment, early intervention would probably be more effective, and evidence exists that an interview with a healthcare professional a few months after starting treatment improves adherence. Biochemical markers of bone turnover could potentially be used for monitoring because they change rapidly in response to treatment and are more predictive of fracture reduction. However, at present within person variability and measurement variability are too great for these markers to be useful in clinical practice." The editorialist concluded: "If true non-responders to antiresorptive treatment do exist they are rare, and most cases of non-response are caused by failure to persist with treatment. This is best tackled by carefully explaining the treatment to patients before they start and follow-up after about three months to discuss problems related to treatment. Routine monitoring of bone mineral density during the first few years of antiresorptive treatment cannot be justified because it may mislead patients, lead to inappropriate management decisions, and waste scarce healthcare resources."
A number of additional evidence-based guidelines and technology assessments have concluded that the clinical utility of measurement of biochemical markers of bone remodeling have not been established. Guidelines on osteoporosis prevention and treatment from the University of Michigan Health System (2011) make no recommendation for the use of biochemical markers in osteoporosis. The guidelines state: "Biochemical markers of bone resorption are used in research and may be used clinically to assess the effectiveness of antiresorptive therapy. In the latter setting, a decrease in these markers to premenopausal levels usually occurs after two to three months of therapy. Some data suggest that elevated levels of bone resorption makers in older women are an independent risk factor for fractures. However, bone markers are not a reliable predictor of BMD, and are not a substitute for DXA in women at risk. Generally, their use in the diagnosis of osteoporosis is not recommended."
An assessment of diagnosis and treatment of osteoporosis by the Swedish Council on Technology Assessment in Health Care (SBU, 2003) concluded that "'[b]iochemical markers are currently a research instrument, and are not used in routine health services."
Guidelines from the Scientific Advisory Council of the Osteoporosis Society of Canada (Brown et al, 2002) concluded: "Bone turnover markers should not yet be used for routine clinical management. Additional studies are needed to confirm their use in individual patients."
Guidelines on osteoporosis from the Scottish Intercollegiate Guidelines Network (2007) stated that "[b]iochemical markers of bone turnover should have no role in the diagnosis of osteoporosis or in the selection of patients for BMD measurement." Guidelines from the Royal College of Physicians (2002) on glucocorticoid-induced osteoporosis stated that the role of monitoring the effects of bone-sparing agents in glucocorticoid-induced osteoporosis using biochemical markers of bone turnover "has not been established." The guidelines state that "[r]eported changes in specific resorption markers in response to glucocorticoids have been inconsistent." The guidelines also note that bone resorption markers may be affected by changes in inflammatory activity and hence a decrease following initiation of glucocorticoid therapy may reflect suppression of disease activity rather than reduced bone resorption.
Royal College of Nursing (2005) guidelines on osteoporosis and menopause stated: "Biochemical markers of bone turnover measured by a urine test are currently being researched and in the future could provide primary care settings with a practical means of monitoring response to treatment." Royal College of Nursing (2005) guidelines on osteoporosis and breast cancer stated that "biochemical markers of bone turnover detectable in a urine test are currently being investigated."
British Society of Gastroenterology guidelines on osteoporosis in inflammatory bowel disease and celiac disease stated that biochemical markers of bone remodelling "may prove useful in practice to assess the efficacy of treatment and the need to change to another agent" (Lewis and Scott, 2007). British Society of Gastroenterology guidelines on osteoporosis associated with chronic liver disease stated that "serum bone markers may prove useful in assessing response to treatment in the future in individuals without chronic liver disease" (Collier et al, 2002). The guidelines stated, however, "as the levels are affected by the extent of hepatic fibrosis and none of these markers has been studied in patients with chronic liver disease, they cannot yet be recommended as a means of assessing bone loss and the risk of fracture in cirrhotic patients."
An assessment by the Australian Medical Services Advisory Committee (MSAC, 2003) of the Ostase test for the mass measurement of serum bone alkaline phosphatase concluded that there is insufficient evidence of the effectiveness and cost-effectiveness of Ostase in the diagnosis and monitoring of osteoporosis. Guidelines from the Royal Australian College of General Practitioners (O'Neill et al, 2004) stated that biochemical markers of bone remodeling are "rarely needed" in primary care practice.
Guidelines from the Institute for Clinical Systems Improvement (2011) stated that "[a]t this time there is no consensus about the routine use of serum and/or urine markers of bone turnover in the evaluation of patients with osteoporosis."
Guidelines on osteoporosis from the Kaiser Permanente Care Management Institute (2008) stated: "There is no recommendation for or against routine bone turnover testing with biochemical markers for monitoring women and men taking antiresorptive therapy for osteoporosis." This conclusion was based upon an "I" grade of evidence, based upon a finding that the evidence that this intervention is effective "is lacking, of poor quality, or conflicting and the balance of benefits, harms, and costs cannot be determined."
A synthesis of guidelines on screening and risk assessment for osteoporosis in post-menopausal women by the National Guideline Clearinghouse (2011) stated: "There is overall agreement that [biochemical markers of bone formation and resorption] do not predict BMD nor reliably estimate fracture risk and that their routine use in clinical practice is not recommended."
Regarding biochemical markers of bone remodeling, guidelines on osteoporosis from the American College of Obstetricians and Gynecologists (2008) stated that "the value of such markers in routine clinical practice has not been established." Guidelines on menopause and osteoporosis from the Society for Obstetricians and Gynaecologists of Canada (2009) made no recommendation for the use of biochemical markers of bone turnover in the management of osteoporosis.
Guidelines from the American Association of Clinical Endocrinologists (2003) stated that biochemical markers may have a role in fracture risk assessment and monitoring of therapy. They stated, however, that the role of biochemical markers in clinical management has not been established: "Currently, the precise role of biochemical markers in the clinical management of osteoporosis has not been established. Several confounding issues must be resolved before a clear role for these measurements can be determined. Age, gender, menopausal status, meals, diurnal variation, and certain medications all influence resorption marker levels and can cause extreme variability. Moreover, a relationship has not been demonstrated between changes in bone marker levels after treatment and reduced fracture risk. In addition, the relationship between changes in bone marker levels and bone balance is unclear."
Guidelines from the World Health Organization (WHO, 2003) stated that changes in biochemical markers at menopause "are insufficiently discriminatory, however, to provide a diagnostic test for osteoporosis", and their use in monitoring individuals "requires further study because of their precision errors and biological variation." The guidelines concluded that "[b]iochemical indices for skeletal turnover may be useful in risk assessment, but further research is needed to determine their value in clinical practice to monitor treatment." The guidelines recommended that further research should be carried out on the evaluation of biochemical markers of bone turnover in clinical practice.
American College of Preventive Medicine guidelines on osteoporosis screening (Lim et al, 2009) concluded that biochemical markers "cannot replace BMD testing" and are "not useful for population-based screening". The guidelines explained that "[t]hese biochemical markers of bone turnover are often used in the research setting but have limited clinical utility." The guidelines noted that they may be useful in monitoring response to therapy, but that "[t]hey do not predict bone mass or reliably estimate fracture risk."
Guidelines on the use of bisphosphonates in multiple myeloma from the American Society for Clinical Oncology (2007) concluded: "The use of biochemical markers of bone metabolism to monitor bisphosphonate use is not suggested for routine care because of a lack of prospective studies validating such an approach."
A UK National Health Service (NHS Oxfordshire, 2008) statement found insufficient evidence that biochemical monitoring improves compliance or reduces fracture risk. The statement noted that P1NP is one of a number of biochemical markers of bone turnover that could be measured to monitor compliance and response to drug therapy. The statement indicated that there are are no trials looking at the role of serum P1NP measurement in the management of any group or sub-group of patients on long-term drug treatment for osteoporosis. The report described a randomized controlled trial comparing urinary marker measurement with no measurement in post-menopausal women on drug treatment which showed that women who had positive marker results were more likely to persist with treatment than women who did not have marker measurement. However, women who had negative marker results were more likely to give up treatment than those who had no marker measurement. The report also cited a small randomized trial on post-menopausal women on drug treatment compared "nurse monitoring" with "urinary marker measurement and nurse monitoring" and "no monitoring". Patients in the "nurse monitoring" and "marker and nurse monitoring" groups were more likely to persist with treatment than those with "no monitoring". However, both monitored groups were equally likely to persist, and marker measurement made no difference to compliance. The statement indicated that there are no trials looking at the role of monitoring by any marker test in specific groups such as patients considering "drug holidays" from long-term treatment or patients on teriparatide treatment. The statement reported: "There is no trial evidence showing any impact of treatment monitoring (by any method) on fracture rates." The statement noted the need for appropriately designed studies of the role of monitoring in improving compliance and reducing fracture risk.
The ASCO executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer (Van Poznak et al, 2011) stated that the use of biochemical markers to monitor bone-modifying agents use is not recommended.
Guidelines on screening for osteoporosis in men (Qaseem et al, 2008) and on the pharmacologic treatment of osteoporosis (Qaseem et al, 2008) from the American College of Physicians included no recommendation for the use of biochemical markers. Guidelines on osteoporosis from the International Society for Clinical Densitometry (ISCD, 2007) and the Michigan Quality Improvement Consortium (2010) also included no recommendation for the use of biochemical markers. In addition, guidelines from the National Institute for Health and Clinical Excellence (NICE, 2008) on pharmacologic treatments for the prevention of osteoporotic fragility fractures included no recommendation for the use of biochemical markers in diagnosis, selection of therapy, monitoring, fracture risk assessment or any other indication.
Guidelines on osteoporosis from the British Columbia Medical Services Commission (2011) state, regarding bone turnover markers: "[a]t present no single or combined assay is recommended except in specific circumstances. Assays have a proven use in research studies involving large samples but they are complex and variation is too great to be useful at the individual level."
Medicare's coverage of biochemical markers for osteoporosis is not the result of a systematic evidence review, or a determination by the Agency for Healthcare Research and Quality about the clinical utility of these tests.
The labeling for Food and Drug Administration (FDA)-approved osteoporosis treatments made no recommendation for the use of biochemical markers in the diagnosis of osteoporosis, or in the selection, dosing, or administration of these drugs.
Lee and Suzuki (2010) examined if serum CTX could pre-operatively predict the risk of developing osteonecrosis of the jaws (ONJ) from oral bisphosphonates (BPs). These researchers hypothesized that there is no clinical correlation between the observed pre-operative serum CTX values and the risk of developing ONJ. The authors examined the scientific basis (validity) of the morning fasting serum CTX test in 163 consecutive patients who underwent various oral surgery procedures in the office. The authors also reviewed the laboratory test results and the recommended protocol based on the test values. A total of 163 patients (mean age of 75.9 years) were divided into 2 groups: (i) group I was the control group that consisted of 109 patients taking oral BPs who did not take the CTX test pre-operatively, and (ii) group 2 consisted of 54 patients taking BPs and who elected to have the CTX test performed to assess their level of risk of developing ONJ, pre-operatively. Both groups of patients were observed for a period of 8 weeks for signs and symptoms of BP-associated ONJ after surgery. The clinical data at 8 weeks and beyond revealed that there was no evidence of BP-associated ONJ in all participants. The authors concluded that the serum CTX is not a valid pre-operative test to accurately assess the level of risk of developing ONJ and is not indicated in the oral surgery patient.
Tolouian et al (2010) evaluated urinary NTX as a marker of bone turnover in chronic kidney disease (CKD). These investigators studied the relationship between bone-specific alkaline phosphatase (BSAP), parathyroid hormone (PTH) and urine NTX/creatinine (Cr) in 37 CKD out-patients. In a multi-variate model, PTH had a positive correlation with BSAP ( r= 0.44, p < 0.19) and U-NTX/Cr (r = 0.55, p < 0.30), after adjusting for age, gender, estimated glomerular filtration rate (GFR), serum phosphorus, corrected calcium, and race. However, the strongest correlation was found between the 2 direct markers of bone resorption and formation (U-NTX versus BSAP; r = 0.80; p < 0.0001), suggesting a tight coupling of bone resorption and formation in CKD. The effect of gender on U-NTX/Cr was studied in a multi-variate model after adjusting for age, race, GFR, serum calcium, phosphorus and PTH. Females had a higher U-NTX/Cr than males. The authors concluded that these findings indicated that urinary NTx, a promising marker of bone resorption in CKD patients, exhibits a strong positive correlation with other markers used to assess renal osteodystrophy (i.e., PTH and BSAP). Unlike PTH and BSAP, urine NTX also measures bone loss secondary to osteoporosis.
Homocysteine (Hcy) is a sulfur amino acid. Recent studies suggest that Hcy may affect bone metabolism, bone quality as well as fracture risk in humans; and circulating Hcy may be used as a risk indicator for osteoporosis. Gjesdal et al (2006) reported that plasma total Hcy has been associated with hip fracture, but not directly with BMD. On the other hand, Morris et al (2005) stated that Hcy and vitamin B12 status indicators are associated with BMD in older Americans. Whether this association reflects a causal relation remains unclear and merits further study in light of age-related declines in B12 status and BMD, and the need for low-risk, easily implemented strategies for osteoporosis prevention.
There is currently insufficient evidence to support measurements of plasma Hcy for evaluating the risk of fracture. In fact, Ravaglia et al (2005) reported that low serum folate is responsible for the association between Hcy and risk of osteoporotic fracture in elderly individuals. Hermann and colleagues (2005) stated that initial findings indicate that Hcy is not only a risk indicator, but also a player in bone metabolism. Moreover, existing data open speculation that folate, vitamin B6 and vitamin B12 act not only via Hcy-dependent pathways, but also via Hcy-independent pathways. However, these investigators stated that more studies are needed to clarify the mechanistic role of Hcy, folate, vitamin B6 and vitamin B12 in bone metabolism. Current evidence-based guidelines make no recommendation for Hcy measurement for diagnosis, monitoring, or risk assessment in osteoporosis.
Gjesdal et al (2006) examined the association of hip BMD with levels of plasma total Hcy (tHcy), folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C polymorphisms. Bone mineral density was measured between 1997 and 2000 in 2,268 men and 3,070 women, aged 47 to 50 and 71 to 75 years, from the Hordaland Homocysteine Study cohort. Low BMD was defined as BMD in the lowest quintile for each sex and age group. Linear, logistic, and generalized additive regression models were used. Plasma levels of tHcy were inversely related to BMD among middle-aged and elderly women (p < 0.001) but not among men. The multiple adjusted odds ratio for low BMD among subjects with high greater than or equal to 15 uM/L [greater than or equal to 2.02 mg/L]) compared with low (less than 9 uM/L [less than 1.22 mg/L]) tHcy level was 1.96 (95 % confidence interval [CI]: 1.40 to 2.75) for women and was not significant for men. Additional adjustments for plasma folate level or intake of calcium and vitamin D did not substantially alter the results. Plasma folate level was associated with BMD in women only. The authors observed no association between BMD and vitamin B12 level or the MTHFR polymorphisms; and they concluded that elevated tHcy and low folate levels were associated with reduced BMD in women but not in men. These findings suggest that tHcy may be a potential modifiable risk factor for osteoporosis in women.
Selhub (2006) stated that data from several studies suggest that mild elevation of plasma Hcy is a risk factor for occlusive vascular disease. In the Framingham studies it was shown that plasma tHcy concentration is inversely related to the intake and plasma levels of folate and vitamin B-6 as well as vitamin B-12 plasma levels. Almost 2/3 of the prevalence of high Hcy is attributable to low vitamin status or intake. Elevated plasma Hcy concentration is a risk factor for prevalence of extra-cranial carotid artery stenosis of at least 25 % in both men and women. Prospectively elevated plasma Hcy is associated with increased total and cardiovascular diseases mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. This multitude of relationships between elevated plasma tHcy and diseases that afflict the elderly points to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is Hcy itself or whether Hcy is merely a marker remains to be determined. This is in agreement with the editorial of van Meurs and Uitterlinden (2005) who stated that "despite the potential limitations of the study by Sato et al (2005), the results show that at least in patients following stroke, folate and vitamin B12 supplementation is effective in preventing hip fracture. Whether a similar effect can also be obtained in other (high fracture risk) patients can only be answered by other interventional studies. After the initial observation of association between circulating homocysteine levels and fracture risk less than 1 year ago, these results now support a causal link. However, final proof of causality will have to come from elucidation of the biological mechanism underlying this relationship".
Perier and colleagues (2007) noted that Hcy has recently been described as an independent risk factor for osteoporotic fractures in the elderly. These investigators prospectively followed women belonging to the OFELY study during a mean follow-up of 10 years. Homocysteine was measured at baseline in 671 post-menopausal women from the OFELY cohort (mean age of 62.2 +/- 9 years). Incident clinical fractures were recorded during annual follow-up and vertebral fractures were evaluated with radiographs every 4 years. A Cox proportional hazards model based on time to first fracture was used to calculate hazard ratios for quartiles of Hcy values. Mean Hcy was 10.6 +/- 3.4 mumol/L, increasing with age. After adjustment for age, Hcy was significantly associated with physical activity, calcium intake, serum albumin and serum creatinine; but not with bone turnover markers and BMD. During a mean follow-up of 10 years, 183 fractures occurred among 134 women. After adjustment for age, the overall relative risk of fracture for each 1 SD increment of Hcy was 1.03 (95 % CI: 0.87 to 1.31). Fracture risk was higher in women with Hcy in the highest quartile without adjustment but no longer after adjustment for age. The authors concluded that Hcy is not an independent risk factor of osteoporotic fractures in healthy post-menopausal women from the OFELY cohort with a broad age range.
Rhew et al (2008) examined the relationship of baseline Hcy levels with BMD and incidence of fractures over 2 years in women with and without systemic lupus erythematosus (SLE). Women with SLE (n = 100) and without SLE (n = 100) were matched according to age (+/- 5 years), race, and menopausal status. Data were collected from 1997 to 2004, including hip, lumbar spine (L-spine), and distal forearm BMD, serum Hcy levels, and a self-administered questionnaire on osteoporosis risk factors, medications and symptomatic fractures at baseline and 2-year follow-up. Analyses were performed to compare Hcy levels, BMD, and incident fractures and to evaluate the relationship of Hcy with BMD and incident fractures in both groups. Mean Hcy +/- SD was higher (p < 0.001) in women with SLE (9.88 +/- 3.8 micromol/L) than in women without SLE (7.98 +/- 2.6 micromol/L). Women with SLE had significantly lower L-spine BMD Z-scores, while hip BMD Z-scores and distal forearm BMD T-scores were non-significantly lower than in women without SLE. No significant correlations were observed between Hcy and BMD in either group. A total of 13 women with SLE experienced new fractures, while 4 women without SLE had new fractures over 2 years (p = 0.035); however, there was no association between Hcy levels and incident fractures in either group. The authors concluded that women with SLE had significantly greater baseline Hcy, lower L-spine BMD, and more new fractures over 2 years, compared with women without SLE. However, Hcy levels were not significantly associated with BMD and did not predict new fractures in women with or without SLE over 2 years.
Zhu et al (2009) examined the effects of Hcy and MTHFR genotype on hip bone loss (as indexed by BMD) and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70 to 85 years. Nutritional intake and prevalent fracture status were assessed at baseline, plasma Hcy was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographical report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of co-variance and Cox proportional hazard regression. The highest tertile of Hcy was associated with a greater hip BMD loss over 4 years (-2.8 %) compared to the middle (-1.6 %) and lowest tertiles (-1.2 %) (p < 0.001). This effect remained after adjustment for co-variates. There was no effect of Hcy on fracture prevalence or incidence. Gene variation in MTHFR was only weakly related to one of the bone outcome measures. The authors concluded that in this study population, high Hcy is associated with greater hip bone loss but not fracture risk.
Vasikaran and associates (2011) determined the clinical potential of bone turnover markers (BTMs) in the prediction of fracture risk and for monitoring the treatment of osteoporosis. Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001. High levels of BTMs may predict fracture risk independently from BMD in post-menopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. Bone turnover markers provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTMs and by inadequate quality control. The International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine recommend one bone formation marker (serum procollagen type I N propeptide [PINP]) and one bone resorption marker (serum CTX) to be used as reference markers and measured by standardized assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine. The authors concluded that BTMs hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.
Funck-Brentano et al (2011) stated that serum BTMs (sBTMs) are used in clinical practice for patients undergoing post-menopausal osteoporosis therapy. These researchers analyzed the literature on the ability of sBTMs to monitor therapy, focusing on the following 5 objectives: (i) pre-treatment values and treatment choice; (ii) short-term changes and clinical response; (iii) sBTMs effect on persistence to therapy; (iv) sBTMs ability to predict fracture risk after withdrawal of therapy; and (v) the prediction of serious adverse effects. A systematic search on Medline completed manually was performed until November 2010 and was limited to post-menopausal osteoporosis and marketed therapies. Following the PRISMA statement for systematic reviews, a total of 48 studies were selected. Baseline sBTMs levels were not able to predict fracture risk reduction with either treatment. There was more evidence for the prediction of fracture risk reduction with bone formation sBTMs including PINP than with serum CTX. Most of the studies found correlations between sBTMs and BMD changes under anti-resorptive therapies, although inconsistently. The only published study on the impact of sBTMs on persistence to therapy showed negative results. There was no evidence that sBTMs allow the prediction of adverse effects, especially osteonecrosis of the jaw. The authors concluded that sBTMs reflect the skeletal effects of anti-osteoporotic treatments. Pre-treatment values are not recommended for selecting therapy. Short-term changes are significantly correlated with BMD variation, but there is no published evidence that they predict benefit on fracture risk at the individual level.
Biver and colleagues (2012) noted that osteoporosis diagnosis is based on BMD but bone remodeling is also a crucial issue. It can be assessed by BTMs. Their interest for the positive and etiological diagnosis of osteoporosis at baseline, and their predictive value for past asymptomatic vertebral fractures, were evaluated by a systematic review of the literature. Medline database was searched to identify all published reports analyzing BTMs and BMD or fractures. These investigators conducted meta-analyses on BTMs levels according to osteoporotic status using random effects models. Moderate and negative correlations were found, mainly in post-menopausal women, between BTMs and BMD, especially with bone alkaline phosphatase (bone ALP), osteocalcin, serum C-terminal and urine N-terminal cross-linking telopeptides of type I collagen (serum CTX and urine NTX). Bone ALP and serum CTX levels are higher in osteoporotic patients compared to controls. High levels of bone ALP in primary hyper-parathyroidism and low levels of osteocalcin in endogenous hypercorticism are the most relevant data reported in endocrine diseases associated with osteoporosis. High levels of BTMs, especially osteocalcin, bone ALP or serum CTX, may be associated with prevalent vertebral fractures. The authors concluded that the diagnostic value of BTMs at baseline in osteoporosis is very low. The interest of BTMs for the etiological diagnosis of secondary osteoporosis has not been demonstrated. Furthermore, they stated that data are lacking to address the interest of BTMs assessment to screen for vertebral fractures in asymptomatic patients with high-risk factors of fractures.
An UpToDate review on "Use of biochemical markers of bone turnover in osteoporosis" (Rosen, 2013) states that "The use of biochemical bone turnover markers (BTMs) in clinical trials has been helpful in understanding the mechanism of action of therapeutic agents. However, their role in the care of individual patients is not well established. Biologic and laboratory variability in BTM values have confounded their widespread use in clinical practice …. There is no consensus on a role for BTMs in the diagnosis of osteoporosis or the selection of candidates for therapy. There is currently insufficient data to support the use of BTMs for deciding when to restart bisphosphonate therapy after a drug holiday or for the assessment of risk (osteonecrosis of the jaw) in bisphosphonate-treated patients undergoing invasive dental procedures".
Garnero et al (2013) stated that sclerostin, an osteocyte soluble factor, is a key regulator of bone formation. Circulating sclerostin levels were reported to increase with age and to be modestly associated with BMD and bone turnover, but there are no data on the association with fracture risk. In a population of 572 post-menopausal women (mean age of 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures that occurred in 64 subjects. These researchers investigated 572 post-menopausal women (mean age of 67 ± 8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new 2-site ELISA and spine and hip BMD by DXA, serum β-isomerized CTX, intact N-terminal PINP, intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 post-menopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5 to 7 years) follow-up, 64 post-menopausal sustained an incident fracture. Serum sclerostin correlated positively with spine (r = 0.35, p < 0.0001) and total hip (r = 0.25, p < 0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r = -0.10, p = 0.014) and CTX (r = -0.13, p = 0.0026) and with intact PTH (r = -0.13, p = 0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture. The authors concluded that serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in post-menopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.
In a prospective cohort study, Amrein et al (2014) evaluated the association between levels of circulating sclerostin and laboratory parameters of bone and mineral metabolism, BMD and quality measured using quantitative ultrasound (QUS), fracture risk, and mortality. Female nursing home residents aged 70 and older (mean 84 ± 6; n = 539) included in this study. Serum sclerostin, bone turnover markers, and BMD and quality were measured at baseline. Participants were followed for clinical fractures and all-cause mortality. Partial correlation analysis adjusted for age, weight, and renal function revealed a significant positive correlation between sclerostin levels and calcaneal stiffness and radial and phalangeal speed of sound (all p < 0.01) and a significant negative correlation between sclerostin levels and osteocalcin, serum CTX, and PTH (p < 0.05). After a mean follow-up of 27 ± 8 months, 139 participants (26 %) had died and 64 had a hip or other non-vertebral fracture (12 %). Sclerostin was not predictive of mortality. In women with a negative fracture history, it was significantly but not linearly associated with fracture risk. The authors concluded that in institutionalized elderly women, there is a significant relationship between serum sclerostin levels and QUS indices, bone turnover, and PTH, but sclerostin was not strongly associated with important clinical outcomes. Thus, it remains unclear whether sclerostin is a clinically useful predictor of fractures or mortality, at least in this setting.
Lewerin et al (2014) noted that cobalamin deficiency in elderlies may affect bone metabolism. These researchers examined if serum cobalamins or holotranscobalamin (holoTC; the metabolic active cobalamin) predicts incident fractures in old men. Men participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) Sweden cohort and without ongoing vitamin B medication were included in the present study (n = 790; age range of 70 to 81 years). During an average follow-up of 5.9 years, 110 men sustained X-ray-verified fractures including 45 men with clinical vertebral fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls, prevalent fracture, tHcy, cystatin C, 25(OH)D, intake of calcium, and physical activity (fully adjusted)), increased per each standard deviation decrease in cobalamins (hazard ratio (HR), 1.38; 95 % CI: 1.11 to 1.72) and holoTC (HR, 1.26; 95 % CI: 1.03 to 1.54), respectively. Men in the lowest quartile of cobalamins and holoTC (fully adjusted) had an increased risk of all fracture (cobalamins, HR = 1.67 (95 % CI: 1.06 to 2.62); holoTC, HR = 1.74 (95 % CI: 1.12 to 2.69)) compared with quartiles 2 to 4. No associations between folate or tHcy and incident fractures were seen. The authors presented novel data showing that low levels of holoTC and cobalamins predicting incident fracture in elderly men. This association remained after adjustment for BMI, BMD, tHcy, and cystatin C. However, any causal relationship between low cobalamin status and fractures should be explored in a prospective treatment study.
An UpToDate review on "Use of biochemical markers of bone turnover in osteoporosis" (Rosen, 2015) states that "The use of biochemical markers of bone turnover (BTMs) for managing osteoporosis is not a central component of most osteoporosis guidelines. When BTMs are addressed, guideline committees typically recommend against their routine use, due to the limitations of measuring and interpreting BTMs in individual patients. Most committees agree that a potential role of BTMs is monitoring osteoporosis therapy to identify non-responders. However, prospective trials to define the most optimal approach for incorporating markers into management strategies are needed".
Summer et al (2014) stated that identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/or osteolysis and to improve understanding of disease progression. There have been several new reports since the last systematic review (which covered research through mid-2008) justifying a new assessment. These researchers sought to determine which biomarkers have the most promise for early diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty. They performed a systematic review using MEDLINE and EMBASE databases, covering the period through December 2013, and identified 1,050 articles. They restricted the definition of biomarker to biomolecules and imaging parameters useful for diagnosis and monitoring of disease progression, only including articles in English. These investigators chose 65 articles for full review, including 44 from the original search and 21 from subsequent hand searches. They used the 22 articles in which patients with total joint arthroplasty who had aseptic loosening and/or peri-implant osteolysis unrelated to sepsis had been compared with patients with total joint arthroplasty with stable implants. There were 90 comparisons of these 2 patient populations involving 35 different biomarkers. Diagnostic accuracy was assessed in 9 of the 90 comparisons with the highest accuracy found for tartrate-resistant acid phosphatase 5b (0.96), although a separate comparison for this biomarker found a lower accuracy (0.76). Accuracy of greater than 0.80 was also found for cross-linked n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The most studied markers, tumor necrosis factor-α and interleukin-1β, were found to differ in the affected and control groups in less than 30 % of the comparisons. Thirty of the 35 biomarkers were studied in 4 or fewer separate comparisons with nearly 50 % of the biomarkers (17) studied in only 1 comparison. Many of the comparisons were not able to eliminate a number of confounding variables, and there was only 1 prospective study. The authors concluded that currently, there are no validated biomarkers for early diagnosis and monitoring of the biological sequelae of wear or tribocorrosion, although there are some promising leads, including markers of bone turnover.
|CPT Codes / HCPCS Codes / ICD-10 Codes
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":
|CPT codes not covered for indications listed in the CPB:
|Collagen cross links, any method
|Cyanocobalamin (Vitamin B-12)
|Cyanocobalamin (Vitamin B-12); unsaturated binding capacity
|Osteocalcin (bone g1a protein)
|Other CPT codes related to the CPB:
|Ultrasound bone density measurement and interpretation, peripheral site(s), any method
|Computed tomography, bone mineral density study, one or more sites
|77080 - 77081
|Dual energy X-ray absorptiometry (DXA), bone density study, one or more sites
|84075 - 84080
|Phosphatase, alkaline
|ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
|Age-related osteoporosis with or without current pathological fracture
|Idiopathic aseptic necrosis of bone, other site [jaw] [not covered for evaluating risk of developing bisphosphonate-induces jaw osteonecrosis]
|Chronic kidney disease (CKD)
|Osteogenesis imperfecta
|Mechanical loosening of internal prosthetic joint
|Periprosthetic osteolysis of internal prosthetic joint
|Encounter for screening for osteoporosis
|Asymptomatic menopausal state


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Heifetz plays Beethoven & Spohr
1 CD / Idis / 2005-11-24Works: Ludwig van Beethoven: Concerto for Violin in D major, Op. 61; Romance for Violin and Orchestra no 1 in G major, Op. 40; Romance for Violin and Orchestra no 2 in F major, Op. 50; Louis Spohr: Concerto...
Performers: Heifetz, Jascha [Violin]
Conductors: Munch, Charles; Steinberg, William; Solomon, Izler
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Archived Story
'It can wait'Published 2:20pm Tuesday, October 1, 2013
Hartselle students make pledges to not text and drive
Hartselle High School students were challenged to make a pledge to stop texting while driving Thursday afternoon.
Dave Hargrove, regional director for AT&T Alabama, said that one of the leading causes of death for teens is automobile crashes. A large percentage of those crashes are due to distracted driving.
"Ninety-seven percent of teens and 98 percent of adults know that it's unsafe to text while driving," Hargrove said. "However, we do it anyway."
"We're constantly checking our smartphones whether its buzzing or not," he added. "It's important that we learn to leave it alone or ask someone else in the car to check it for us.
"I have a sign that's hanging in my car to remember not to text while driving. I have to remind myself not to do that."
To help drive home the point, Hargrove showed the film entitled "From One Second to the Next." The presentation highlighted stories of people who were affected by crashes that were caused by someone texting while driving.
"On average, it takes about five seconds to send a text message. That's five seconds that your eyes aren't on the road," Hargrove said.
In addition to Hargrove's presentation, the student body watched a film produced by former student Caitlin Beard, who did an anti-distracted driving video for her Gold Award project for Girl Scouts. Beard is now a student at Troy University.
"It's something that we've had to live with for the last 14 years," said Kathy Beard, her mother. "Her older sister was killed when her car was struck by a train. Distracted driving played a part in that crash."
Beard said that she was proud of her daughter producing the video.
"She did a great job with it," Beard said. "She did it to raise awareness about distracted driving."
Beard said the video has not yet been posted on YouTube. Her family has shared it with a few others before showing it to the Hartselle High School student body.
Hargrove said those wishing to make the pledge may do so by logging on to www.itcanwait.com.


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4137 Atmore St., Charlotte, NC 28205
- $85,000
- 1+ Years on site
- Est: $315/month
Estimate Your Monthly Payment
- Mortgage Center
- Beds: 4
- Baths: n/a
- Multi-Family Home
- 1,784 sq ft
Great opportunity to purchase duplex with great income potential, property is zoned B2 and have tenants with monthly rents of $530 each. Please do not disturb tenants and opportunity to preview properties will be during due diligence period. Property must be sold with adjacent property, 4129 Atmore Street, MLS #2214368
- Year Built: 1953
- 1+ Years on site
- Multi-Family Home
- Beds: 4
- Baths: n/a
Listing Details
- Building Units
- 2 Units in Building
- Lot Size
- Approximately 0.43 Acres
- Parking
- Gravel/Crushed Stone Driveway, Parking Space(1)
- Features
- Brick Exterior
- Heating
- Gas Forced Air
- Sewer
- Public/City
- Water
- City, Gas Hot Water Heater
Public Facts: As provided by County Assessor and Recorder offices. May not reflect recent additions or improvements. If you see any errors, the best way to get the records updated is to contact your local county records office. If any of the information in this section conflicts with property information provided by a listing agent or broker, agent-provided information should be deemed more reliable.
Local Info
| Median Household Income
| Median Years In Residence
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| Households with Children
| Percent of Homes Rented
Nearby Elementary Schools
- Sugar Creek Charter
- 4101 N Tryon St
- Shamrock Gardens Elementary
- 3301 Country Club Dr
- Highland Mill Montessori
- 3201 Clemson Ave
Nearby Middle Schools
- Sugar Creek Charter
- 4101 N Tryon St
- Kipp: Charlotte
- 931 Wilann Dr
- Martin Luther King Jr Middle
- 500 Bilmark Ave
Nearby High Schools
- Garinger High
- 1100 Eastway Dr
- Crossroads Charter High
- 5500 North Tryon Steet
- Cochrane Collegiate Academy
- 6200 Starhaven Dr
These are the closest schools to your requested location. Proximity does not guarantee enrollment eligibility. Please consult your real estate agent or school district to confirm the schools you are zoned to attend.
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TricTrac Meeple Tour! Marcel's Journey...
- tom-le-termiteUnited States
ft lauderdale
So, remember when Jeff Schaefer started the crazy idea of a globe-circling Meeple?Recommend
Well, on TricTrac , the French Equivalent of BGG, we decided to also create our own Meeple Tour.
We customized a Meeple, that we called, "Marcel le Meepouic" (The "Pouquie" is the TricTrac symbol)...
..and we started the plan to travel all over France, going from city to city, from famous places to unknown localities.
The story started on March 5th 2009 in Avignon, and Marcel finished his journey in Orléans on February 19th 2010. Just about a year for 53 cities!
All TricTrac user who volunteered were in charge of Marcel, and hadhave to document the journey with many pictures of their locality, and tell about the amazing adventures that happened to him.
All the pictures and stories were regularly updated on http://trictracmeepletour.over-blog.com/ , at least once a weak, and all the great pictures are available there.
I originally wasn't thinking about relaying about this event on BGG, but some of the pictures from the Trictrac users and the story they created are full of imagination an creativity.
Today, I wish to share these pictures and stories with you, and I hope you will enjoy them, as much as we did on TricTrac.
Please, don't hesitate to clic on each city link, there are much more great pictures... and the more cities Marcel has been through, the crazier the pictures get!
Again, all the pictures and stories can be found on http://trictracmeepletour.over-blog.com/
- Edited Fri Mar 12, 2010 4:52 pm
- Posted Fri Jun 26, 2009 8:25 pm
- [+] Dice rolls


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Army emphasizes sexual assault prevention, strives to educate
April 8, 2013
By Mary Barczak
As the month of April begins, the Army's attention turns to the Sexual Harassment/Assault Response Prevention program.
Sexual assault is any unwanted contact. Sexual harassment is an inappropriate joke or comment. Master Sgt. William Umbleby, Fort Knox's sexual assault awareness coordinator, said one-third of sexual assaults are preceded by some sort of sexual harassment. If court-martialed for sexual assault Soldiers can be dishonorably discharged or face up to 30 years in prison.
Though the SHARP program is fairly new, Umbleby said he thinks it has had a good impact on the Army. It was established by former Army Chief of Staff Gen. George Casey in 2008 to address various scandals. Two years later, officials at Fort Knox really started pushing the program and getting individuals trained in the program, Umbleby said. There is a SHARP representative in every directorate on post and even more victim advocates.
"(Even one assault is) one too many," he said. "We are a band of brothers and sisters and if we can fight next to each other than we should be able to take care of each other."
Before the program was formed, people may not have known how or where to report an incident of assault, Umbleby said, but now it is mandatory for every Soldier and civilian employee to take a sexual assault seminar once a year.
There have been nine reported cases of Soldier and Family member sexual assaults this fiscal year at Fort Knox.
"Each case is different," Umbleby said.
But all of these specific ones have involved women ages 18 to 20, were alcohol related and divided between on-and off-post occurrences. There is a sexual assault review board that meets once a month for Fort Knox to examine trends of the incidents.
Most cases are reported through the crisis hotline, said Umbleby, which is manned 24 hours a day. If a call is missed the responders have 10 minutes to call the person back. After reaching callers, the victim advocate explains their rights as victims. Then callers must choose whether to make their cases restricted or unrestricted. Restricted means they can still receive medical treatment and counseling without disclosing any identifying information about their attackers. If they go this route, the gathered evidence is put into a box for five years in case victims change their minds.
Unrestricted means the person can receive medical treatment and counseling but chooses full disclosure of information about their attackers to those who need to know such as their chain-of-command and the criminal investigation command.
"However, if you want to prosecute," Umbleby said, "the case must be unrestricted."
A word of advice, he added. If victims initially seek the help of military police or Criminal Investigation Division then they waive the right to have their case be restricted, he said.
Educating the community about sexual assault has helped people to come forward, Umbleby said.
"We are try to get away from the victim focus and promote bystander intervention, victim care and going after offenders," Umbleby said.
In his experience, one of the most common reasons why victims don't make a report is because they will have to retell and therefore relive the experience.
The ultimate goal of the five year SHARP campaign is to eliminate the culture where sexual assault and sexual harassment is OK, Umbleby said.
"We need to make people aware that these still do happen and they need to stand up and do something about it," he said. "And I think that conviction starts with the Army Values."
The month's events will include two information fairs, one today from 10 a.m. until 2 p.m. at the Heritage Room at the Saber & Quill and a second on April 11 at the same place and time. The event is open to the community.
Umbleby said there will be more than 20 agencies present at the fair to help educate and build awareness about sexual assault.
The third event, "Take Back the Night," will take place tonight from 7:30 to 9 p.m. at the Saber & Quill on the Verandah. Community members can come together to show their stand against sexual violence.
Further, SHARP will have a 5k Fun Run/Walk on April 27 at 9 a.m. at Gammon Physical Fitness Center. Registration begins at 7 a.m. and the safety brief will be at 8:45 a.m. This event is free and open to the community. The purpose of the walk is to raise sexual harassment and assault awareness along with promoting Family fitness, health and camaraderie.


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Ex-England goalkeeper Paul Robinson was fined £1,000 for speeding yesterday.
The 33-year-old player's lawyer asked magistrates to take into account his short-term career when deciding the penalty.
Blackburn Rovers keeper and captain Robinson, 33, a former England No. 1, was clocked doing 93mph on the 60mph A59 near Beamsley, North Yorkshire, in his BMW M5 on the afternoon of October 4.
His solicitor John Batty told magistrates in Skipton, North Yorkshire, Robinson, who already had three points on his licence, accepted he had done wrong and was prepared to accept a driving ban.
He also pointed out his client was a high earner and his pay "exceeded the norm" but said he was in a short-term career and asked it be taken into account when considering a fine.
The court heard Robinson was overtaking a wagon on a three-lane section of road when he was spotted by a police officer.
He told the officer he had accelerated to pass a wagon that had indicated to move into his lane.
Mr Batty said Robinson, of Knaresborough, North Yorkshire, who was unable to attend court because of work commitments, was a professional sportsman who travelled hundreds of miles between his home and workplace.
On top of the fine magistrates endorsed Robinson's licence with six points handed him a £100 victims surcharge and £45 costs.
A further three points would put him at risk of a ban.


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With Tropical Storm Isaac approaching the northern Gulf Coast, many banks have closed some branches in Louisiana and Florida before the weather gets worse. Banks will make on-the-fly decisions to reopen when it is deemed safe to do so. Normal business is expected to resume on Thursday.
Tropical Storm Isaac is expected to reach hurricane speeds on Tuesday and its path indicates that landfall will occur at southeast Louisiana.
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Capital One closed all southeast Louisiana branches early on Monday. Branches will remain closed on Tuesday and Wednesday, but some may reopen early if the weather improves.
Chase said it will close all branches in the New Orleans and Houma areas on Tuesday and Wednesday. The bank kept some Louisiana and east Texas branches open late on Monday to help customers conduct their banking before the storm.
Whitney Bank announced temporary closures of all Louisiana branches located south of Lake Pontchartrain for Tuesday. The bank will make regular updates on its website of which branches will be open and closed.
Capital One, Chase and Whitney Bank have the most branches in Louisiana, with a combined total of more than 500 branches locations in the state, according to the FDIC.
Citibank is telling customers to use its branch locator tool to find branches that will offer full service as Isaac hits the southeastern United States. Some Citibank branches in Florida closed as early as Monday.
"Should you be affected by Hurricane Isaac, we offer special services during emergency situations. We're ready to provide financial recovery solutions to those affected, including access to cash and waiving fees," Citibank said in a notice on its site homepage.
Smaller banks near the Gulf Coast region have closed some branches as well.
Depending on the severity of Isaac, bank branches may open as soon as Wednesday.
In all cases, bank customers are encouraged to call ahead to find out which branch location is open and whether or not the bank can offer any relief in this time of distress. Also, online and mobile banking will remain a viable option for customers who need to manage their finances.
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5 Stocks at Risk of Falling off the Fiscal Cliff
Warren Buffett's portfolio as of the most recently reported period. Computer SciencesFully one-third of technology services company Computer Sciences' (CSC - Get Report) $16 billion revenue base is tied to government contracts. In fact, almost every government agency uses CSC in some capacity, from the Navy to the IRS to motor vehicle departments. You can already see government budget pressures impacting this company. Fiscal first-quarter sales (ended June) rose just 1% from a year ago, the lowest growth rate in recent memory. In fact, revenues tied to commercial customers rose roughly 7%, offset by a 7% shrinkage in government work. >>8 Tech Stocks Leading the Market The fiscal cliff only exacerbates the pressure. Even if the lawmakers strike some sort of last-minute agreement to avert such a drastic move, they will still likely take a hatchet to any non-essential government spending, so projects such as IT modernization programs -- CSC's bread and butter -- are likely to be deferred or outright eliminated. As of now, EPS for CSC is expected to drop from $3.24 in fiscal (March) 2012 to around $2.20 a share in the current fiscal year. Yet analysts see EPS rebounding back up towards the $3 mark in fiscal 2014, though that will be virtually impossible to achieve if the government's IT budget shrinks further, as many suspect. Life Technologies The U.S. government has long prided itself as a global leader in basic science research. From the National Science Foundation to the National Institutes of Health, billions have been spent on the sciences, often using this company's lab equipment. Well, under the fiscal cliff scenario, spending on basic science and research would take a quick double-digit haircut, affecting such companies as Life Technologies (LIFE) as well as science lab equipment providers Sigma-Aldrich (SIAL) and Thermo-Fisher Scientific (TMO). Life also shows up on a recent list of 10 Stock Picks of the Highest-Rated Money Managers. Raytheon Defense contractor Raytheon (RTN - Get Report) clearly saw U.S. spending pressures coming and has been pushing to beef up its international business. The trouble is that governments elsewhere are also feeling pinched. That helps explain why Raytheon posted a book-to-bill of just 0.94 in the June quarter (which is a measure of new orders compared to revenues, and any number below 1.0 means backlog is shrinking).GD shows up in
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Paige Denim
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ISLAND CITY — One man was arrested by law enforcement officers late Thursday afternoon in Island City following a raid made to curb drug trafficking.
Joshua Ryan Alvarez, 21, of Island City was arrested at his residence at 10100 S. Sterling St. in Island City on charges of possession of a controlled substance, distribution of a controlled substance and manufacture of a controlled substance.
"The arrest was made to intercept and interrupt drug trafficking,'' said Capt. Craig Ward of the Union County Sheriff's Department.
Ward said that illegal drugs were located but no other details were provided.
The raid was made at 5:40 p.m. by law enforcement officers armed with a search warrant. The agencies involved included the Union-Wallowa Drug Task Force, Oregon State Police, Union County Sheriff's Office and La Grande Police Department.Alvarez is set to appear in Union County Circuit Court at 9 a.m. on Nov. 26.


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- Homepage >
- News Archives >
- Article
82nd Association Convention brings together past and present Paratroopers
August 24, 2009
Story Highlights
- The 82nd Airborne Division Association held its 63rd National Convention Aug. 19-22
- Paratroopers of different eras came together to bond over their similar experiences
- Events took place all week to honor past and present troopers and recognize wounded warriors
- A Vietnam veteran was also awarded the Silver Star, 40 years after his heroic performance in Vietnam
FORT BRAGG, N.C. - Two Paratroopers sat at a patio table covered with empty plastic cups, drinking, laughing and sharing war stories about their time with the 82nd Airborne Division.
One was a young man in his twenties, his muscular forearms bearing numerous tattoos; the other was an older gentleman sporting a distinguished gray mustache and a World War II Veteran baseball hat.
Paratroopers of different eras came together to bond over their similar experiences during the 63rd 82nd Airborne Division Association National Convention held in Indianapolis, Ind. from August 19-22.
The convention is held every year in a different city. Its purpose is to bring together veterans and current active duty soldiers of the 82nd.
Steven Frazer, the association president, raises money and visits with Wounded Warriors from the division.
"We try to make sure they're comfortable, that they're not forgotten and that they're welcomed back," Frazer said.
This year, the association raised money so 42 wounded Paratroopers would be able to attend the convention at no cost. Their plane tickets, hotel rooms and other necessities were paid for by donations from the association's many chapters.
The troopers were welcomed to Indianapolis with a dinner where all were given a lifetime memberships to the 82nd Association.
"It's a great reunion," Frazer said.
The Convention officially kicked off on the 20th when three C-130 Hercules aircrafts landed at Mt. Comfort Airfield in Indianapolis carrying about 150 Paratroopers.
The 82nd Chorus and Color Guard performed at various events throughout the week.
On August 20, the Chorus sang the National Anthem at a minor league baseball game in Indianapolis while the Color Guard presented the colors.
Immediately after, the Chorus was given a police escort to rush down the street to Lucas Oil Stadium. They again sang the National Anthem, this time during the pre-game show for the Indianapolis Colts football game against the Philadelphia Eagles.
The following day, the chorus went to the Riley Hospital for Children and the Peyton Manning Children's Hospital to visit with and perform for the sick children admitted there.
Young Cole Branigan, 5, was delighted when several chorus members visited his room and performed an impromptu version of "Rockin' Robin."
Also that afternoon, the Marriott Indianapolis East, where the convention was being held, dedicated a newly erected fountain in the courtyard of the hotel to the military.
Brent Myrick, the general manager of the hotel, said several American Legion and Veterans of Foreign Wars groups hold conventions at the hotel, so he felt it was appropriate for the hotel staff to show their support.
"We wanted to have an opportunity to dedicate this fountain and say thank you," Myrick said.
That evening, the association thanked those who lost their lives while serving the 82nd by holding a memorial dinner to honor fallen troopers.
On August 22, a formal banquet was held to wrap up this year's convention.
At the banquet, Viet Nam veteran Darrell Ormes received a Silver Star for his bravery during his time with the 82nd. The entire room stood at attention as Ormes was presented with the award, for which he had waited more than 40 years to receive.
Being a Paratrooper is a special accomplishment to many soldiers in the division, both past and present, and events like these remind soldiers of why they're proud to be in the 82nd, many veterans said.
"There hasn't been a day I've been here that I haven't thought about my time in the 82nd", said Greg Fulbright, who was in the division from 1983-1985.
"I get to meet and talk to seven decades of troopers," Fulbright said.
"I wouldn't trade the experience for anything."


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Comics Alliance Interview
5 weeks ago
Musings from Jim Sorenson and a few guest bloggers about Transformers, character models, science-fiction, comic books, and whatever else is on our minds.
Bombshell looks incredible. Do you have any ideas as to what his voice might sound like in Animated?
Continually a good place to visit for art.


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Political Hay
Daschle Disconcerted
Only a liberal would find free speech taxing. Has he finally tired of calling Rush Limbaugh a big fat idiot?
Sixties liberals never thought free speech dangerous until conservatives wielded it against them. Recall that even as Bill Clinton commanded the bully pulpit of the presidency, he whined about Rush Limbaugh's uncontested "three hours" on the air, and then suggested that terrorist Timothy McVeigh had fallen under the influence of right-wing talk show hosts.
Recall also that in the 1990s, after the Republican takeover of Congress, some liberal college professors, many of whom had launched their careers as unruly advocates of free speech, began high-minded "civility" discussions at American universities. Too much "extremism" -- which just meant that conservatives were finally challenging them -- had them knitting their brows over the abuse of the First Amendment.
This trend continues with Senator Tom Daschle's oddball attack on Rush Limbaugh this week. The Democratic leader who rose to power through cheap-shot critiques of the Reagan years suddenly sounds like an embattled conservative establishment pol from the 1960s: "What happens when Rush Limbaugh attacks those of us in public life is that people aren't just content to listen. People want to act because they get emotional…and the threats to those of us in public life go up dramatically, against us and against our families, and it's very disconcerting."
Borrowing a page from Clinton, Daschle sees a parallel between the wild fundamentalism abroad and the harsh rhetoric of "Rush Limbaugh and all the Rush wannabes" at home.
Daschle's remarks about Limbaugh will prove as credible and persuasive as his pre-election pouting about George Bush's supposed questioning of the Dems' patriotism. When liberals have been reduced to complaining about free speech and too much passion in politics, it is clear they have lost their way.
Now out of power, are Daschle and the Democrats likely to adopt a civil tone? No, they will return to the rebellious free speech and emotional demagoguery that Daschle finds so conveniently worrisome in Limbaugh.
Liberals do not like being beaten at their own game. They can whip up activists, drive the homeless to the polls, hurl insults at politicians they deem dangerous, riot outside registrar's offices, and play to the emotions shamelessly. But woe to Republicans when they do the same. The Dems' windy rhetoric about the value of robust speech, gadfly protests, and unconventional agitating is proportionate to their power: when they have got it, they speak like Voltaire; when they don't, they think like Mussolini.
How long before the liberals now fretting about incivility start calling Limbaugh a "big fat idiot" again? If conservatives called Michael Moore a big fat idiot, liberals would put down their Al Franken book and champion Moore as an idealist vital to the health of the Republic.
Yes, Limbaugh is dangerous, but only to the careers of liberal politicians. Obtusely attacking him will not resuscitate their careers because Limbaugh is now more mainstream than they are. If these "populist" pols want to take the pulse of America, they would do well to tune in, not out. Limbaugh's success is due not to demagogic magic or circus acts -- fresh from his "Saturday Night Live" performance, John McCain is calling Limbaugh a "clown" -- but to effective and entertaining truth-telling. Were demagoguery and charisma enough to corral an enormous audience, the radio shows of Mario Cuomo and Alan Dershowitz would not have flamed out so quickly.
Afraid of losing viewers, many members of the media have wised up about Limbaugh and see no point in marginalizing him. As the Washington Post's Howard Kurtz notes, "Tom Brokaw and Tim Russert had him on their Election Night coverage," and in recent years Brian Williams and Ted Koppel have given him a respectful hearing too.
But liberal politicians who need votes as badly as the media need viewers remain behind the curve, clumsily swinging at Limbaugh as a figure of the fringe as they get closer to it.


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No chances by PhobsWatch
©2010-2016 Phobs
I don't know why I decide to draw it xD
I don't know why I decide to draw it xD
That man will either shoot himself later or live with eating his own words.
the sass on the third (ringo?) one's face XD
Their faces are just pure perfection.
their faces xD
John Lennon's face. Every time.
Buahahahah XD
If he knew :3...
Greatest band of all time ^^
я всегда любила этот рисунок, он казался мне таким ИДЕАЛЬНЫМ и ТОЧНЫМ, что я даже не задумывалась, что у него может быть автор, что его кто-то нарисовал вообще. Я не могу выразить свое восхищение твоим творчеством, спасибо за твои работы
Oh my gosh, I love how you drew them! They have so much character! <3
Love it~
oh dear xDDDD
when I think about it, it really is a lame name for a band ... XD
john is just having none of that monkey's shit today
Хахаха, забавно)))
well he was wrong!
*___* awesome
Различить "битлов" можно только по носам xDD
so much love for this.
Nice job!!
JHA! yeah, sure...
Loved it <3
Loved it <3
Beatles <3
that is all!! XD
that is all!! XD
Paullll, aw his face D: I love Ringo's bemused face
Beatles ftw
John and Ringo are not impressed.
Paul's cheeks are so pinchable, it's adorable.
their noses are all dark they must be drunk!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
How much the dude would shoot himself if he knew how things turned out?
lol, cool.
This is adorable.
This is adorable.
Okay, so I know its John and then Paul, but then George Ringo or Ringo George? Still, dont you love moments like that?
Haha! Wonderful!
"We don't like their sound. Groups of guitars are on their way out."
Verbatim quote from Decca Records executive in regards to the Beatles when they auditioned. Sweet, sweet irony...
Verbatim quote from Decca Records executive in regards to the Beatles when they auditioned. Sweet, sweet irony...
LOL so wrong he is- this's funny XD