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United States District Court, C.D. California, Western Division
March 19, 2014
S.W. by and through his Guardian Ad Litem WANDA WILLIAMS, Plaintiff,v.CAROLYN W. COLVIN, ACTING COMMISSIONER OF SOCIAL SECURITY ADMINISTRATION, Defendant.
PAUL L. ABRAMS, Magistrate Judge.
Wanda Williams ("plaintiff"), on behalf of S.W., [1] filed this action on May 6, 2013, seeking review of the Commissioner's denial of S.W.'s application for Supplementary Security Income payments. The parties filed Consents to proceed before the undersigned Magistrate Judge on June 7, 2013, and January 27, 2014. Pursuant to the Court's Order, the parties filed a Joint Stipulation on January 27, 2014, that addresses their positions concerning the disputed issues in the case. The Court has taken the Joint Stipulation under submission without oral argument.
On September 28, 2009, plaintiff filed an application seeking Supplemental Security Income payments on behalf of her minor grandson, S.W., alleging that he has been disabled since April 2, 2008, due to attention deficit hyperactivity disorder and bi-polar disorder. [Administrative Record ("AR") at 19, 94-98, 102.] After the application was denied initially and upon reconsideration, plaintiff requested a hearing before an Administrative Law Judge ("ALJ"). [AR at 66-69, 71-77.] A hearing was held on May 24, 2011, at which time plaintiff and S.W. appeared with counsel and both testified. [AR at 35-63.] A medical expert ("ME") also testified. [AR at 38-44.] On August 22, 2011, the ALJ determined that S.W. was not disabled. [AR at 19-30.] When the Appeals Council denied plaintiff's request for review of the hearing decision on December 7, 2012, the ALJ's decision became the final decision of the Commissioner. [AR at 6-10, 14, 274-75.] This action followed.
Pursuant to 42 U.S.C. § 405(g), this Court has authority to review the Commissioner's decision to deny benefits. The decision will be disturbed only if it is not supported by substantial evidence or if it is based upon the application of improper legal standards. Moncada v. Chater , 60 F.3d 521, 523 (9th Cir. 1995); Drouin v. Sullivan , 966 F.2d 1255, 1257 (9th Cir. 1992).
In this context, the term "substantial evidence" means "more than a mere scintilla but less than a preponderance - it is such relevant evidence that a reasonable mind might accept as adequate to support the conclusion." Moncada , 60 F.3d at 523; see also Drouin , 966 F.2d at 1257. When determining whether substantial evidence exists to support the Commissioner's decision, the Court examines the administrative record as a whole, considering adverse as well as supporting evidence. Drouin , 966 F.2d at 1257; Hammock v. Bowen , 879 F.2d 498, 501 (9th Cir. 1989). Where the evidence is susceptible to more than one rational interpretation, the Court must defer to the decision of the Commissioner. Moncada , 60 F.3d at 523; Andrews v. Shalala , 53 F.3d 1035, 1039-40 (9th Cir. 1995); Drouin , 966 F.2d at 1258.
To qualify for disability benefits, a child under the age of eighteen must have "a medically determinable physical or mental impairment, which results in marked and severe functional limitations, and which can be expected to result in death or which has lasted or can be expected to last for a continuous period of not less than 12 months." 42 U.S.C. § 1382c(a)(3)(C)(i).
The Commissioner (or ALJ) follows a three-step sequential evaluation process in assessing whether a child is disabled. 20 C.F.R. § 416.924. In the first step, the Commissioner must determine whether the child is currently engaged in substantial gainful activity; if so, the child is not disabled and the claim is denied. Id . If the child is not currently engaged in substantial gainful activity, the second step requires the Commissioner to determine whether the child has a "severe" impairment or combination of impairments causing more than minimal functional limitations; if not, a finding of nondisability is made and the claim is denied. Id . If the child has a "severe" impairment or combination of impairments, the third and final step requires the Commissioner to determine whether the impairment meets, medically equals, or functionally equals an impairment in the Listing of Impairments ("Listings") set forth at 20 C.F.R., Part 404, Subpart P, Appendix 1; if so, disability is conclusively presumed and benefits are awarded; if not, a finding of nondisability is made and the claim is denied. 20 C.F.R. § 416.924.
In this case, at step one, the ALJ found that S.W. "was a school-age child on September 28, 2009, the date [the] application was filed, " and that he "has not engaged in substantial gainful activity since" that date. [AR at 22.] At step two, the ALJ concluded that S.W. has the severe impairment of hyperactivity. [Id.] At step three, the ALJ determined that S.W.'s impairment does not meet, medically equal, or functionally equal any impairment in the Listings. [Id.] As a result, the ALJ concluded that S.W. is not disabled. [AR at 30.]
Plaintiff contends that: (1) the ALJ erred at step three in considering whether S.W.'s alleged impairments equaled impairments in the Listings; (2) the ALJ improperly relied on the ME's opinion because the ME did not review all of the evidence; and (3) the ALJ erred in rejecting S.W.'s grandmother's testimony and other third party reports. [Joint Stipulation ("JS") at 3-10, 13-15, 17-22, 24.]
In determining whether a child's impairment or combination of impairments functionally equals an impairment in the Listings, the Commissioner must assess the child's functioning in six domains: (1) acquiring and using information; (2) attending and completing tasks; (3) interacting and relating with others; (4) moving about and manipulating objects; (5) caring for oneself; and (6) health and physical well-being. 20 C.F.R. § 416.926a(a)-(b). To functionally equal an impairment in the Listings, the child's impairment or combination of impairments must result in a "marked" limitation in two of the domains or an "extreme" limitation in one domain. 20 C.F.R. § 416.926a(d). A "marked" limitation is one that "interferes seriously with [the child's] ability to independently initiate, sustain, or complete activities." 20 C.F.R. § 416.926a(e)(2). By contrast, an "extreme" limitation is one that "interferes very seriously with [the child's] ability to independently initiate, sustain, or complete activities." 20 C.F.R. § 416.926a(e)(3).
Plaintiff argues that the ALJ's step three finding here that plaintiff's impairment or combination of impairments does not functionally equal an impairment in the Listings is not supported by substantial evidence. [JS at 3-10, 13-14.] Specifically, plaintiff contends that the medical evidence, including standardized test scores, demonstrates that S.W. has a "marked" impairment in three of the six domains: "Acquiring and Using Information, Attending and Completing Tasks, and Interacting and Relating [with] Others." [JS at 5.]
Between 2009 and 2011, plaintiff was administered various standardized tests, including the California Achievement Test ("CAT"), four administrations of "District Wide Assessments, " and the "California Standards Test." [AR at 146, 239.] S.W.'s 2009 CAT results in "Math" and "Reading" each yielded a "National Percentile Rank" of 2, while his scores in "Science" and "Spelling" each yielded a "National Curve Equivalent" score of 0.[2] [Id.] Based on his California Standards Test scores in "English-Language Arts" and "Math, " S.W. was assigned a proficiency level of "F[ar] B[elow] B[asic]." [Id.]
In his decision, the ALJ concluded that S.W. "[d]oes not have an impairment or combination of impairments that meets or medically equals one of the listed impairments." [AR at 22.] Specifically, in his assessment of the six domains, the ALJ assessed S.W. as having a "less than marked limitation" in "acquiring and using information" and "attending and completing tasks." [AR at 25-26.] With regard to "interacting and relating with others, " "moving about and manipulating objects, " "the ability to care for himself, " and "health and physical well-being, " the ALJ found "no limitation." [AR at 27-29.]
The ALJ's step three decision that plaintiff's impairment or combination of impairments does not functionally equal an impairment in the Listings is not supported by substantial evidence because the ALJ failed to acknowledge S.W.'s standardized test results. [See AR at 24-29]; Reddick v. Chater , 157 F.3d 715, 722-23 (9th Cir. 1998) ("In essence, the ALJ developed his evidentiary basis by not fully accounting for the context of materials or all parts of the testimony and reports."); Gallant v. Heckler , 753 F.2d 1450, 1456 (9th Cir. 1984) ("Although it is within the power of the [Commissioner] to make findings... and to weigh conflicting evidence, he cannot reach a conclusion first, and then attempt to justify it by ignoring competent evidence in the record that suggests an opposite result.") (internal citation omitted.) Social Security regulations specifically provide that when such test results are available, they are the preferred method of documentation for purposes of assessing the severity of functional limitations. See 20 C.F.R. pt. 404, subpt. P, app. 1, § 112.00(C) ("In most functional areas, there are two alternative methods of documenting the required level of severity: (1) Use of standardized tests alone, where appropriate test instruments are available; and (2) use of other medical findings.... The use of standardized tests is the preferred method of documentation if such tests are available."); 20 C.F.R. § 416.926a(e)(ii) ("The medical evidence may include formal testing.... When you have such scores, we will consider them together with the information we have about your functioning to determine whether you have a marked' or extreme' limitation in a domain.") (emphasis added). The ALJ failed to acknowledge these test results at all, let alone address evidence that S.W. performed "[f]ar [b]elow [b]asic" on several of the tests. [AR at 146, 239]; see Noel ex rel. J.A.W. v. Colvin, 2013 WL 6797697, *3 (C.D. Cal. Dec. 20, 2013) ("The ALJ noted that a speech/language pathologist conducted an evaluation in April 2010, but inexplicably failed to consider the [formal test] scores and, specifically, the fact that [claimant]'s valid scores were three standard deviations below the mean pursuant to 20 C.F.R. § 416.926a(e)(3)(ii). This was error."). Moreover, the ALJ erred to the extent he failed to explain why he did not rely upon S.W.'s standardized test scores in reaching his step three decision. 20 C.F.R. § 416.926a(e)(4)(iii)(B) ("When we do not rely on test scores, we will explain our reasons for doing so in your case record or in our decision."). Accordingly, the ALJ's decision that S.W. does not medically or functionally equal any Listing is not supported by substantial evidence and remand is warranted on this claim.
Plaintiff contends that the ALJ erred in failing to properly consider the testimony and written statements of plaintiff, S.W.'s grandmother. [JS at 18-22, 24.]
In determining the severity of a claimant's impairments and how the impairments affect his ability to work, lay witness testimony[3] by friends and family members who have the opportunity to observe a claimant on a daily basis "constitutes qualified evidence" that the ALJ must consider. Sprague v. Bowen , 812 F.2d 1226, 1231-32 (9th Cir. 1987); accord Stout v. Comm'r of Soc. Sec. Admin. , 454 F.3d 1050, 1053 (9th Cir. 2006); Smolen v. Chater , 80 F.3d 1273, 1288 (9th Cir. 1996); 20 C.F.R. §§ 404.1513(d)(4), (e), 416.913(d)(4), (e). Such testimony "is of particular value" because those who see a claimant every day can often tell whether he is suffering or merely malingering. Smolen , 80 F.3d at 1289 (citation omitted). While an ALJ is not required "to discuss every witness's testimony on a[n] individualized, witness-by-witness basis, " Molina v. Astrue , 674 F.3d 1104, 1114 (9th Cir. 2012), he may discount the testimony of lay witnesses only for "reasons that are germane to each witness." Dodrill v. Shalala , 12 F.3d 915, 919 (9th Cir. 1993); Regennitter v. Comm'r of Soc. Sec. Admin. , 166 F.3d 1294, 1298 (9th Cir.1999).
In an undated Disability Report, plaintiff reported details of S.W.'s aggressive behavior, anger, difficulty focusing, and poor impulse control. [AR at 134.] She stated that S.W. often does not go to bed "at a decent hour because he is so full of energy, " and that "every morning" he "jumps with a whole lot of energy." [Id.] She also indicated that it is difficult to get S.W. to focus on tasks such as getting dressed for school or doing his homework because he is "angry one minute and happy the next minute." [Id.] She reported that S.W. "won't take a bath, brush his teeth or wash his face, " and that when she tries to make him do these things, "he runs[, ] shout[s] and yell[s]." [AR at 136.]
At the administrative hearing, plaintiff testified that S.W. receives special tutoring at the YMCA for additional help with reading and math, that he has difficulty paying attention at school, and that he is "hyper" at home until she gives him his medicine, after which "he ends up going to sleep." [AR at 52-53.] She also explained that S.W. attends monthly counseling, sees a psychiatrist at Kaiser Permanente, and that he is waiting to get into group therapy. [AR at 57.]
In his decision, the ALJ's only reference to plaintiff's allegations is his statement that they are "credible to the extent that the claimant has a medically determinable impairment which could be expected to produce some symptomatology, ... [but] the record as a whole does not support the allegations as to the extent, intensity and functionally limiting effect." [AR at 23.]
The ALJ's reason for rejecting plaintiff's allegations is too vague to achieve the level of specificity required for rejecting a lay witness' testimony. See Stout , 454 F.3d at 1054 ("the ALJ, not the district court, is required to provide specific reasons for rejecting lay testimony"); Carton v. Colvin, 2013 WL 3884030 at *6 (E.D. Wash. July 26, 2013) (finding that "the ALJ's general reference to the lay testimony as not consistent with the preponderance of the evidence' is too vague to constitute even a germane' reason for discounting the statements and comments of plaintiff's lay witnesses") (citation omitted). As a result, the ALJ failed to provide a reason germane to plaintiff for rejecting her allegations regarding S.W.'s functional limitations. See Dodrill , 12 F.3d at 919 ("Disregard of [lay witness statements] violates the Secretary's regulation that he will consider observations by non-medical sources as to how an impairment affects a claimant's ability to work.").
Defendant argues that, "[i]n her third-party statements[, p]laintiff was internally inconsistent, " and asserts that "[s]uch inconsistencies would be a proper basis for finding subjective testimony incredible and would properly serve as a proper basis for rejecting a lay witness[s] testimony." [JS at 23-24.] Defendant's contention is unpersuasive. In his decision, the ALJ did not state that he rejected plaintiff's testimony because it was internally inconsistent. [See, generally, AR at 19-30.] "Long-standing principles of administrative law require [this Court] to review the ALJ's decision based on the reasoning and factual findings offered by the ALJ - not post hoc rationalizations that attempt to intuit what the adjudicator may have been thinking." Bray v. Comm'r of Soc. Sec. Admin. , 554 F.3d 1219, 1225-26 (9th Cir. 2009) (citation omitted).
Where lay witness evidence is improperly rejected, that evidence may be credited as a matter of law. See Schneider v. Barnhart, 223 F.3d 968, 976 (9th Cir. 2000) (finding that when lay evidence rejected by the ALJ was given the effect required by the Commissioner's regulations, it became clear that the plaintiff's limitations were sufficient to meet or equal an impairment in the Listings); see also Colombo v. Astrue, 2011 WL 2693203, at *8 (W.D. Wash. July 11, 2011) (recognizing holding in Schneider); Sexton v. Astrue, 2010 WL 2888975, at *10 (C.D. Cal. July 21, 2010) (same). Because the ALJ failed to give any legally adequate reason to reject plaintiff's lay witness statements, let alone any reason that is germane to plaintiff, the Court credits as true plaintiff's statements concerning S.W.'s daily activities and his limitations resulting from his impairments. On remand, the ALJ should take into account plaintiff's statements in determining whether S.W. is disabled.[4]
The Court has discretion to remand or reverse and award benefits. McAllister v. Sullivan , 888 F.2d 599, 603 (9th Cir. 1989). Where no useful purpose would be served by further proceedings, or where the record has been fully developed, it is appropriate to exercise this discretion to direct an immediate award of benefits. See Benecke v. Barnhart , 379 F.3d 587, 595-96 (9th Cir. 2004); Varney v. Sec'y of Health and Human Servs. (Varney II) , 859 F.2d 1396, 1401 (9th Cir. 1988); see also Lingenfelter v. Astrue , 504 F.3d 1028, 1041 (9th Cir. 2007). Where there are outstanding issues that must be resolved before a determination can be made, and it is not clear from the record that the ALJ would be required to find plaintiff disabled if all the evidence were properly evaluated, remand is appropriate. See Benecke , 379 F.3d at 593-96; Harman v. Apfel , 211 F.3d 1172, 1179 (9th Cir.), cert. denied, 531 U.S. 1038 , 121 S.Ct. 628, 148 L.Ed.2d 537 (2000).
Here, there are outstanding issues that must be resolved before a final determination can be made. However, in an effort to expedite these proceedings and to avoid any confusion or misunderstanding as to what the Court intends, the Court will set forth the scope of the remand proceedings. First, the ALJ is instructed on remand to credit as true plaintiff's statements concerning S.W.'s limitations.
Second, in Issue No. 1, in addition to arguing that the ALJ erred in his step three analysis, plaintiff maintains that the ALJ failed to determine whether several of S.W.'s alleged impairments, including ADHD, mood disorder, and specific learning disability, [5] were severe. [JS at 3.] The Court agrees. On remand, the ALJ shall reevaluate the medical evidence regarding each of these three impairments and explain his reasons for finding them severe or nonsevere in his decision. See Smolen , 80 F.3d at 1290 (explaining that "the step-two inquiry is a de minimis screening device to dispose of groundless claims") (citation omitted); Corrao v. Shalala , 20 F.3d 943, 949 (9th Cir. 1994) ("The Supreme Court has recognized that including a severity inquiry at the second stage of the evaluation process permits the [Commissioner] to identify efficiently those claimants whose impairments are so slight that they are unlikely to be found disabled even if the individual's age, education, and experience are considered.") (citing Bowen v. Yuckert , 482 U.S. 137, 153, 107 S.Ct. 2287, 96 L.Ed.2d 119 (1987)).
Finally, the ALJ shall reevaluate, at step three, whether S.W. meets, or medically or functionally equals in severity, an impairment in the Listings. In making this determination, the ALJ shall address S.W.'s standardized test results in the record and, if he chooses not to rely on any such scores, he shall explain his reasons for doing so. 20 C.F.R. § 416.926a(e)(4)(iii)(B) ("When we do not rely on test scores, we will explain our reasons for doing so in your case record or in our decision."). To the extent the ALJ is required to interpret S.W.'s standardized test scores in terms of standard deviations, he should seek the assistance of an expert, as needed, to fully develop the record so that he can make such an evaluation. 20 C.F.R. § 416.926a(e)(2)(iii), 416.926a(e)(3)(iii); see Fontanez ex rel. Fontanez v. Barnhart , 195 F.Supp.2d 1333, 1357 (M.D. Fla. 2002) ("Th[e] formal testing... did not provide the ALJ (and the district court) with adequate information about [plaintiff's] functioning in terms of percentiles, percentages of delay, or age or grade equivalents. [Plaintiff's] standard scores were not converted to standard deviations so as to be useful in determining whether [plaintiff] had a marked' or extreme' limitation in a domain. Absent standardized tests that measure functional abilities in terms of standard deviations, a judge cannot usually determine the presence or absence of an extreme' or marked' limitation. Contrary to his duty to fully develop the record, the ALJ failed to determine the significance of [plaintiff's] low scores.").[6]
Accordingly, IT IS HEREBY ORDERED that: (1) plaintiff's request for remand is granted; (2) the decision of the Commissioner is reversed; and (3) this action is remanded to defendant for further proceedings consistent with this Memorandum Opinion.
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The Indian Doctor (TV Series)
Watch The Indian Doctor episodes online for free here at Telepisodes via the links provided in each episode page. When a sleepy 1950s Welsh mining town's only doctor dies, the only replacement the union representative could find arrives, straight from India. To everyone's surprise, he's better educated and more cultured then anyone they know, yet friendly and eager to help. His wife however looks down on the 'peasans', compared to viceregal Delhi, and wants him to move to London.
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Town Square
Street naming conventions
Original post made by Anamika, Midtown, on Jul 30, 2007
Comments (2)
a resident of Another Palo Alto neighborhood
on Jul 30, 2007 at 8:48 pm
Not exactly the answer to your question, but I have bought a book from Books Inc at Stanford which lists all the street names in Palo Alto and where the ideas of the names came from. Some have a real history while others are named after someone in the building/planning office. It is a fun book to look at.
a resident of Meadow Park
on Jul 31, 2007 at 5:28 am
I have noticed that "streets" run north south (ish - parallel to El Camino) while "avenues" run east-west (parallel to Oregon Expressway).
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Paris Baguette coming to Mountain View
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Surviving Family Holidays
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Palo Alto Weekly Holiday Fund
For the last 23 years, the Palo Alto Weekly Holiday Fund has given away more than $4 million to local nonprofits serving children and families. When you make a donation, every dollar is automatically doubled, and 100% of the funds go directly to local programs. It's a great way to ensure your charitable donations are working at home.


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Capitalizing on the all too familiar game plan, South Oldham made 15 3-pointers on Saturday against Christian Academy of Louisville for an 82-72. Joe Griffin had a team-high 21 points as four Dragons scored in double figures.
DeHaven Baptist Church has submitted a proposal to the La Grange Historic Districts Commission to tear down a historic building behind the church to create a parking lot.
The Girls Mid-Bluegrass Conference Championship was hosted at South Oldham Middle School this week. South Oldham won the eighth and sixth grade tournament championship while Oldham County claimed the seventh grade title.
Eighth Grade tournament
Forty-nine high school students may soon become Certified Nursing Assistants (CNA) thanks to a new internship program at the Arvin Education Center.
The woods were lovely, dark and deep in Goshen at the Creasey Mahan Nature Preserve's Nature of Christmas event Dec. 3. The nature preserve's Christmas celebration included a holiday bazaar, s'mores, a hay ride, a visit from Santa and other attractions.
The City of La Grange held its annual Light Up La Grange Saturday night throughout the downtown area. Attendees enjoyed visits with Santa, live music, business specials, face painting, hot chocolate, candy canes and more.
Oldham County Judge-Executive David Voegele recently announced a project to help residents give a second life to their fresh trees after the holidays. The trees will be recycled into mulch at no cost to residents as the holidays come to a close.
Despite the rain, many came out to the Pewee Valley Yule Log celebration on Sunday night to enjoy free chili, music performances and meet Santa.
Good dogs got presents too at the Humane Society of Oldham County's Santa Paws event on Dec. 3. The event featured local art and gift baskets and hosted Santa Claus to visit with pets.
Each year, the National Future Farmers of America (FFA) Organization honors FFA members who show the utmost dedication to the organization through their desire to develop their potential for premier leadership, personal growth and career success through agricultural education.
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The real life Miss Havisham: War widow dies leaving behind £100,000 treasure trove of designer clothes she collected over 70 years - and NEVER wore
- Vervia's fiance died at war and after her father died she lived alone
- Each year she travelled abroad and filled suitcases with designer clothes
- Arriving home she would stash the pieces away unworn
- She closed off rooms full of clothes in her County Durham townhouse
- One dress was even found hidden up the chimney
- It has taken a year to sort the incredible collection ready for sale
A £100,000 hoard of vintage clothing has been discovered in dusty old house after the death of a real-life Miss Havisham.
Vervia Todd developed a secret obsession with fine clothing after the death of her fiance during the Second World War, travelling abroad each year to develope her collection, but keeping her amazing wardorbe before the discovery after her death last year.
Vervia, who was 92 when she died last November, never remarried after the tragic loss of her husband in her early twenties, and instead took the annual holidays on her own until the very last years of her life.
Each year she would buy a new suitcase and fill it with the finest specially-made clothing, only to stash it away unpacked upon her return.
Vervia Todd, pictured right on her retirement day, and left at about age 10, died last year leaving a vast collection of vintage couture
Many of the clothes remained hidden for over half a century, with one designer dress even being found up the chimney.
Vervia closed off rooms full of clothes in her three-story townhouse in Houghton Le-Spring, County Durham, hoarding her vast collection of couture and designer pieces over a period of seventy years.
The house gradually fell into disarray and the dusty old rooms remained unchanged for decades, stuck in an eerie time capsule reminiscent of Miss Havisham's decaying mansion in the Charles Dickens novel Great Expectations.
Journalist Emma Pearson wearing a 1940s Fred Howard satin cocktail dress with 1920s fur and diamanté clutch bag and 1950s bow shoes
Part of the incredible 'once in a lifetime' collection of vintage clothing from the 1940s, 50s, 60s and 70s that has been uncovered in Houghton Le-Spring, County Durham which will go on sale in a special ticket only event on the 7th December
The vast collection, which no one realised existed, has taken 13 months to sort an organise
In one of the bedrooms, the faded floral wallpaper is hung upside down, whilst a once-opulent stand-alone bath dominates the archaic bathroom.
Vervia had remained tight-lipped about her phenomenal style stash, with friends and relatives only discovering the stunning collection when they came to empty her home after her death.
Now, the mesmerising collection of vintage dresses, hats and shoes has been uncovered, and is set to sell for the staggering six figure sum.
Vervia's best friend Sheila Ellis, 65, and cousin Ann, have spent over a year uncovering endless trunks in the house where Vervia lived since the age of one.
But now the pair, who are the executors of Vervia's will, are hoping that the clothes will be given a new lease of life by their new owners.
Vervia's fiance tragically died whilst fighting in Arnhem in the Netherlands.
She never married and spent her life alone in the house after the death of her father, Sam Todd, a dental surgeon.
She said it just wasn't meant to be,' said Sheila, a friend of Vervia's for 30 years.
'She was a glamorous lady when she was younger. She had a very good figure, very trim.
Vintage dealer Paula Donaldson looking through the incredible collection, which spans numerous decades of changing fashion from around the world
Journalist Emma Pearson wearing a 1960s linen shift dress and holding up another 60s style dress. Behind her are just a few of the racks of clothes Vervia collected throughout her life
The collection is expected to reach around £100,00, though some pieces are so rare they may go on display, possibly at Beamish Museum
Emma Pearson wearing a 1960s linen shift dress,
1970s wedge sandals and a 1960s woven shopper, left reflected in a
stunning ancient wooden mirror in the house
The house, which is filled with dust-covered antique furniture, has been turned into a workshop over the past year as the collection was sorted and cleaned
Vintage dealer Paula Donaldson has been working with vintage clothing for around ten years and has never come across such a colossal collection
The amazing collection features beautiful eveningwear that was never worn, including this 1940s lilac satin dress
A brocade evening dress from the 1950s remains exactly as it was
This silk printed 1930s dress is over eighty years old and in pristine condition
A cotton day dress from the 1950s features pale pink trim
This 1960s mini dress is typical of the decade's fascination with space age style
A 1950s day dress features a classic hunting scene
The clothing collection includes a 1960s Polly Peck mini dress
This Wool Shirt Waister is from the 1940s
A pale green Crepe de Chine dress is also a 1940s style
Vervia on holiday with her mother Amy and father Sam, a dental surgeon. After her parents died Vervia lived the rest of her life alone in the three story townhouse
Emma Pearson wearing a 1950s patch pocket skirt with a 1950s rockerbilly top and pumps: Friends and relatives only discovered the stunning collection when they came to empty her home after her death
'Off she'd go on holiday, often to Sorrento in Italy, and she'd come back three weeks later and leave the suitcase. We found all of those cases still packed.
'It was absolutely incredible but typical of her, she was one of a kind."
Vervia with her father Major Sam Todd during World War II. Vervia lived with her father until his death, secretly collecting clothes
Paula Donaldson, owner of vintage shop, Dregs of Society, in Whitley Bay, North Tyneside, has been helping to organise the clothing for the upcoming sale.
Paula has been dealing in vintage clothing for around ten years and has never come across such a colossal collection.
She said: 'Nobody knew that she had these.
'She just loved to shop. Even when she was in her 80s, every Thursday or Friday she would go on the bus to Newcastle.
'Even when she was blind she would have her lunch at Fenwicks and go shopping.
'She shopped until she dropped really.
'[Her friend] Sheila knew that she kept things but I don't think she realised the extent until they went up to the attic.'
The Victorian wedding dress of Vervia's mother, Amy, was discovered in the house as well as Vervia's grandmother's Edwardian wedding gown, and it is planned that these dresses will go on display, possibly at Beamish Museum.
Sheila even found one dress stuffed up the chimney, and had thrown it in the rubbish before realising what it was.
'I pulled it from the chimney and to start off with I thought it was a rag, it was absolutely covered in soot,' said Sheila.
'I picked it up and put it in the rubbish pile and saw something glint and when I looked closer I realised it was a Marshall and Snelgrove dress.
'I hoovered all of the soot off it and rubbed it down with tepid water.
'I just thought nothing ventured nothing gained.'
And then Sheila and Ann donned forensic-style overalls before rolling up their sleeves for what would turn out to be a laborious 13 months of uncovering, restoring and repairing the many garments.
Whole rooms in the large townhouse had been closed off for decades at the time of Vervia's death
The house gradually fell into disarray and the dusty old rooms remained unchanged for decades, stuck in an eerie time capsule
But despite her hard-work, the sale will be bitter-sweet for Sheila.
She said: 'I will be delighted to think they're gone to good homes but I'll be sad to see them go because it's taken over a year to get to this stage.'
The collection will be sold at an event at Vervia's house in Houghton le Spring, County Durham, on 7 December. North News, Richmond House, Old Brewery Court, 156 Sandyford Road, Newcastle.
A few of the personal items and toiletries that belonged to Vervia packaged up ready for the sale
A array of vintage lingerie and hosiery, all still in it's original packaging sits on top of a mantle piece . Vervia is described by her friend Shelia as 'a glamorous lady when she was younger. She had a very god figure, very trim'
In addition to rack after rack of clothing, Vervia's collecting also included accessories such as bags and hats like those pictured, as well as jewellery
The house is reminiscent of Miss Havisham's decaying mansion in the Charles Dickens novel Great Expectations
A once-opulent stand-alone bath dominates the archaic bathroom, where it is clear to see the Vervia also enjoyed buying cosmetic products
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Hangboo Food Grade Flexible Feelfree Eliquid - Chinaprice: contact company for price
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5. Small capacity bottled, can supply 5ML, 10ML, 15ML, 20ML, 30ML, 50ML; Big capacity bulk, can supply 1L, 5L, 8L, 10L.
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Published date: November 9, 2015 -
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The Born Loser by Art and Chip Sansom
- August 27, 2013
- From Beginning
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Comments (7) (Please sign in to comment)
I just realized that Mother Gargle's hair is in the shape of a witch's hat. All this time, I just thought she had a lousy stylelist…
There's a label for you, too, dear
From the 1939 movie, "The Women":
"There's a name for you ladies, but it's not used in high society – outside a kennel!"
She would be one of those birthday cake candles that you can't put out.
Enough shame to delete the comment. Now your comment is just hanging in thin air with no support, and everyone wondering what you are getting at. This happens to me all the time.
Every time this woman appears I envision Margaret Hamilton
on her bicycle with that music playing.."doo doot da doot
da dooo dat..doo doot da doot da dooo dat."
There's a certain "air" about a skunk, too.
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Strings (2011 film)
|A major contributor to this article appears to have a close connection with its subject. (January 2012) (Learn how and when to remove this template message)
|Directed by
|Mark Dennis
Ben Foster
|Produced by
|Mark Dennis
Ben Foster
|Written by
|Mark Dennis
|Billy Harvey
Elle LaMont
Daniel Dasent
Chris Potter
Karl Anderson
Jack Lee
|Music by
|Jermaine Stegall
|Mike Simpson
|Edited by
|Mark Dennis
Ben Foster
Release dates
Running time
|98 minutes
|United States
Strings is a 2011 American dramatic thriller film about a musician who discovers his therapist manipulates patients into committing crimes. The film is the product of the Texas filmmaking team, Mark Dennis and Ben Foster. It was written, produced, and directed by Dennis and was produced and directed by Foster on a budget of $65,000.[1] Dennis and Foster graduated from the University of Texas at Austin with degrees in Radio/TV/Film and are both musicians.[2][3] The extremely low-budget film collected major awards at film festivals across the United States in 2011 and 2012.
American film festival screenings[edit]
- Austin Film Festival – October 2011 [4]
- The Breckenridge Festival of Film – June 2011[5]
- Hollywood Film Festival – October 2011 [6]
- Long Island International Film Expo – July 2011[3]
- Route 66 International Film Festival – September 2011[7]
- San Francisco Best Actors (in a) Film Festival – May 2011[8]
- Silver City Film Festival – November 2011 [9]
- SOHO International Film Festival - April 2012 [10]
- The Tri-State Film Festival – September 2012[11]
- Tulsa International Film Festival – September 2011 [12]
- The White Sands International Film Festival – August 2011[13]
One reviewer compared Strings to the work of Christopher Nolan, describing it as "stirring, exciting, and poignant." [14] The movie received DVD distribution with House Lights Media, based in Colorado and digital distribution with The Orchard.[15][16]
The film collected the Best Director Award at the Long Island International Film Expo as well as Audience Awards at The Breckenridge Festival of Film and The White Sands International Film Festival and the award for Best Thriller at the Route 66 International Film Festival.[5][17]
- Best Film at the SOHO International Film Festival [18]
- Best Director (Mark Dennis and Ben Foster) at the Tulsa International Film Festival[19]
- Best Director (Mark Dennis and Ben Foster) at the Long Island International Film Expo[20]
- Audience Award at White Sands International Film Festival[13][21]
- Audience Award at the Breckenridge Festival of Film[5]
- Audience Award at the Silver City Film Festival [22]
- Best Cinematography (Mike Simpson) at the Long Island International Film Expo[20]
- Best Supporting Actor (Jack Lee) at the Long Island International Film Expo[20]
- Best Song (The Greatest Escape, Billy Harvey) at the Breckenridge Festival of Film[23]
- Best Ensemble Cast, San Francisco Best Actors Film Festival[23]
- Best Thriller, Route 66 International Film Festival[17]
External links[edit]
- Official website
- Strings at the Internet Movie Database
- Ain't It Cool News film review
- The Austin Chronicle film review
- ^ http://www.imdb.com/title/tt1340799/
- ^ Centanni Communications (2011-06-21). "Central TX movie STRINGS is official Long Island International Film Expo selection". PRLog. Retrieved 2011-10-26.
- ^ a b "'Strings' to Debut at Bellmore Movies on Sunday - Bellmore, NY Patch". Bellmore.patch.com. 2011-07-09. Retrieved 2011-10-26.
- ^ "AFF Announces 2011 Lineup - Screens Blog". The Austin Chronicle. 2011-09-20. Retrieved 2011-10-26.
- ^ a b c http://www.mainemedia.edu/news/if-it's-tuesday-must-breckenridge-film-alum-finds-fest-success
- ^ "2011 Films | Hollywood Film Festival: Awards, Films, Indies, Hollywood - HollywoodFilmFestival.com". Hollywoodfest.com. 1936-08-18. Retrieved 2011-10-26.
- ^ http://route66filmfestival.net/2011%20ROUTE%2066%20INTERNATIONAL%20FILM%20FESTIVAL%20SCHEDULE.pdf
- ^ "Winners". Thebestactors.com. Retrieved 2011-10-26.
- ^ http://www.silvercityfilmfest.org/2011films.html
- ^ http://www.sfgate.com/cgi-bin/article.cgi?f=/g/a/2012/05/30/prweb9555427.DTL
- ^ Danny, Cohen (29 September 2012). "Independent Film, STRINGS, Screens at the Tri-State Film Festival Today". Yahoo. Retrieved 1 October 2012.
- ^ http://tulsaiff.festivalgenius.com/2011/films
- ^ a b "Welcome to the WSIFF Site". Wsiff.com. Retrieved 2011-10-26.
- ^ Salazar, David (2011-07-10). "Reel Salazars: LIIFE Day 4 Impressions". Reelsalazars.blogspot.com. Retrieved 2011-10-26.
- ^ http://www.imdb.com/company/co0348342/
- ^ http://theorchard.tv/movies/strings-2/
- ^ a b http://www.route66filmfestival.net/2011%20ROUTE%2066%20INTERNATIONAL%20FILM%20FESTIVAL%20SCHEDULE.pdf
- ^ http://www.prlog.org/11861490-soho-international-film-festival-announces-2012-awardees-danny-aiello-tribute.html
- ^ "Tulsa International Film Festival winners announced". Tulsa World. 2011-09-26. Retrieved 2011-10-26.
- ^ a b c "New York film festival Best Director award goes to San Antonio-Austin filmmakers". EnergizedSanantonio.com. Retrieved 2011-10-26.
- ^ "White Sands Film Festival winners announced - Las Cruces Sun-News". Lcsun-news.com. Retrieved 2011-10-26.
- ^ http://www.silvercityfilmfest.org/2011honors.html
- ^ a b "Barry Bergman Management Assisting Billy Harvey Transition". MMF US. 2011-08-01. Retrieved 2011-10-26.


text:
Social media marketing firm Viralheat has launched a platform it says helps developers make apps "more social."
Word-of-mouth marketing platform SocialChorus and cloud-based, real-time marketing analytics platform Anametrix are its first users.
According to Viralheat, the platform allows developers and companies to integrate social data and capabilities like management, engagement, sentiment analysis, publishing and monitoring into their applications.
SocialChorus is using the suite of APIs to provide insights for its customers, Viralheat says. With the integration of the sentiment analysis API, Viralheat says its dashboard delivers real-time feedback on the mood of advocate content and comments.
Per Viralheat, Anametrix uses the new APIs to help customers market more effectively and increase revenue.
Viralheat also says its scalable cloud infrastructure takes care of details like scheduling messages and monitoring conversations in real-time, freeing up developers to focus on their applications.
Viralheat says it has 12,000 customers.
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amadge Review
Love it!
I absolutely love this ring! It is my engagement ring which was purchased a couple years ago.... I am now very excited that there is a matching wedding band to go with it :) I've been wearing this ring for about a 1 1/2 now and in about 50 days will be wearing the matching wedding band which should be arriving today! This ring has all the sparkle with a very unique setting.
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American Apparel Opens in China; Danity Kane to Design Jeans
Also, checking into Fashion Week might not take so long this year, and Seven for All Mankind sweeps through Asia.
• China gets its first installment of American Apparel this weekend, with a store to open in the World Trade Center in Beijing. Because every city needs a go-to for lamé leggings. [WWD]
• Danity Kane is designing a line of jeans for Dollhouse. That is just so fitting we can hardly stand it. [TeamSugar]
• Design You Trust has declared Louis Vuitton the world's most counterfeited fashion brand. They'd probably agree considering all the lawsuits they file. [Design You Trust]
• Peter Som on predicting trends: "I wish I could — then I'd be living on a beach in the Bahamas … We do our homework, but success is definitely not a science." [British Vogue]
• At Fashion Week next month designers like Marc Jacobs, Ralph Lauren, and Vera Wang will check show guests in with "Events GPS, a technology that uses bar codes, scanners, and color-coded virtual seating charts." You know, so they're less likely to start an hour late. [BizBash]
• Seven for All Mankind will expand in Asia with plans to open 30 to 40 new stores in China over the next five years, a slew of new in-store shops in South Korea. [WWD]
• DKNY will team up with City Harvest, the nonprofit food rescue program, to make over fifteen of its vans inspired by its fall/winter campaign. [British Vogue]
• Will Harley Viera-Newton, Dior's newly appointed D.J. and Internet "It" girl, get booked like crazy for New York Fashion Week? Elite seems to think so since they made a very special comp card for her. [Models.com]
• Elettra Wiedemann founded "JustOneFrickinDay.com," an organization that, among other things, is raising funds to build the first solar-powered hospital in Burundi. She enlisted Chris Benz, Rogan, Rag & Bone, Phillip Lim, Giambattista Valli and others to create limited-edition T-shirts for online sale to support the cause. [Fashion Week Daily]
• Heidi Montag released a new single called "Overdosin'," about "when you fall in love with someone … and [you're] just overdosing off of their love." Listen while watching a brilliantly assembled photomontage of Montag frolicking on a beach and stuff. [Us]


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Soul Shoes at The Riverside
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Soul Shoes will be playing classic Motown Northern 60's R&B Crossovers with DJ's Toddy and Annie at the Riverside Priory Ave St Denys Southampton Hampshire 8pm - 12m/n adm £5 great wooden dance floor friendly atmosphere.
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Ride Along The Lincoln Highway
Travel with Rick Sebak on America's first transcontinental highway and check out the changing landscape from Times Square to San Francisco. This road show incorporates culture, history, food, family, traditions and the changing way of the automobile.
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Logbooks (Travelogs), Maps, Episodes, Reviews and tourist information about Beni Department(Bolivia). You can find Reviews and Logbooks (Travelogs), not only about Beni Department, but also about other popular cities in Bolivia from categories such as Foods, Sightseeing, Shopping, and Accomodation.
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text: Announcer: "Ladies and Gentlemen, the following match is scheduled for one fall" Rodrigo walks out as he skips down to the stage, he then turns his back to the crowd for a moment, opening his arms wide before spinning round again and walks to the ring high-fiving fans. He slides under the ropes and stands in the ring Announcer: "Introducing first, from Burgos, Spain, weighing in at 187lbs, Rooodriigoo!!" Carmen walks out and pumps her fist into the air, she then quickly runs down to the ring, momentarily looking at the steel cage above the ring. She slides in and climbs the turnbuckle, waving to fans Announcer: "And introducing his opponent, from Milwaukee, Wisconsin, Weighing in at 140lbs, Carmen Stevenson!" Rhodes CrayJ Lee Let the match commence. Good Luck to you both.


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LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated changes. Therefore, LR11 expression was assessed in a transgenic mouse model of AD and familial AD (FAD) brains. Immunohistochemistry and immunoblotting of LR11 in PS1/APP transgenic and wild-type mice indicated that LR11 levels are not affected by genotype or accumulation of amyloid pathology. LR11 expression was also evaluated based on immunoblotting and LR11 immunostaining intensity in human frontal cortex in controls, sporadic AD, and FAD, including cases with presenilin-1 (PS1) and presenilin-2 (PS2) mutations. Although LR11 was reduced in sporadic AD, there was no difference in protein level or staining intensity between control and FAD cases. The finding that LR11 expression is unaffected in both a mouse model of AD and autosomal-dominant forms of AD suggests that LR11 is not regulated by amyloid accumulation or other AD neuropathologic changes. We hypothesize that LR11 loss may be specific to sporadic AD and influence amyloid pathology through mechanisms independent of substrate–enzyme interactions regulated by FAD mutations.
Alzheimer disease (AD) is a profoundly debilitating condition that is characterized by the progressive degeneration of neural systems involved in regulating mood, cognition, and memory. Neuropathologically, AD is characterized by the formation of 2 pathologic hallmarks, neurofibrillary tangles rich in hyperphosphorylated tau and plaques that are composed primarily of beta-amyloid (Aβ) (1). The mechanisms underlying the pathogenesis of AD are incompletely understood, but the amyloid cascade hypothesis has become the predominant view of AD pathogenesis (2). In the amyloid model, a shift in the processing of the amyloid precursor protein (APP) from nonpathologic metabolites to the increased generation and/or the reduced clearance of Aβ is believed to be the seminal event in AD pathogenesis.
The vast majority of patients with AD have late-onset sporadic AD. In a small number of patients, however, genetic mutations have been discovered that result in more aggressive pathology with earlier disease onset. Mutations in APP and presenilin-1 and -2, components of the γ-secretase complex that cleaves APP and yields Aβ, cause familial forms of AD (FAD) (3–7). Importantly, all known FAD mutations result in the increased production and deposition of Aβ in brain, lending support to the amyloid hypothesis. In sporadic AD, the mechanism of Aβ accumulation in the brain is likely a result of a complex molecular cascade that includes additional factors distinct from those produced by FAD mutations.
In brain tissue of individuals with sporadic AD, we have found a striking reduction in the ApoE receptor LR11/SorLA, particularly in the vulnerable areas of the cortex and hippocampus (8). LR11 is a member of the low-density lipoprotein receptor (LDL-R) family (9–11). The best-studied role of LDL-Rs is in cholesterol regulation through the binding and uptake of lipid-rich particles (12). Recent evidence has highlighted the involvement of lipoprotein receptors and cholesterol metabolism in the regulation of amyloid generation and is beginning to clarify the connection between cholesterol and neurodegeneration (13–15). All members of the LDL-R family can bind the lipid carrier molecule ApoE, and individuals with one or 2 APOE ε4 alleles have an increased risk of developing AD and earlier disease onset. LR11 has additional functional domains and, as a mosaic receptor, may serve many physiological functions, including cargo transport, chaperone-like activity, signaling, and intracellular sorting (16–21). Recently, we and others have shown that LR11 can interact with APP, influence the trafficking of APP, and regulate Aβ levels in vitro and in vivo (22, 23).
It is not clear, however, whether LR11 loss observed in sporadic AD occurs downstream of the AD pathologic cascade or if reduction in LR11 expression could be a proximal contributor to the disease process. To establish whether LR11 can be regulated by amyloid accumulation in vivo, we examined LR11 expression in a transgenic animal model of amyloidosis as well as brains of individuals carrying FAD mutations. The transgenic mice used in this study were engineered to express the human presenilin-1 (PS1) gene with exon 9 deletion as well as the Swedish APP mutation, both of which were identified in familial forms of the disease (24). Individuals with FAD and the PS1/APP mice are similar in the underlying mechanism of amyloid pathology, one that is believed to be different in origin from that found in sporadic AD.
In this study, we show that unlike sporadic AD, LR11 protein expression is unchanged in PS1/APP mice and FAD brain tissue, suggesting that LR11 is not simply regulated by amyloid or downstream molecular events that follow amyloidosis. These observations provide support for the hypothesis that LR11 loss is a proximal event in sporadic AD and potentially a key component of the complex pathologic cascade that causes sporadic AD. Given the continually growing body of evidence concerning ApoE receptors and amyloidosis, LR11 may play a role in the development of sporadic AD. Taken together with the recent evidence that LR11 regulates Aβ production both in vitro and in vivo, LR11 may prove to be an important therapeutic target for AD.
Double transgenic PS1ΔEx9/APPswe mice were acquired from David Borchelt (Johns Hopkins University). Amyloid accumulation in these mice has been previously characterized with diffuse and neuritic plaque pathology occurring at or before 6 months of age (24). Brains from 3-, 6-, 9-, and 18-month-old mice were hemisected. One hemisphere was prepared for immunohistochemistry as described subsequently, and the cortex was dissected from the remaining hemisphere and homogenized using a Konte tissue grinder for biochemical measurements.
Hemibrains of PS1/APP transgenic mice and control mice were immersion-fixed with 4% paraformaldehyde for 3 hours at 4°C, then cryoprotected in 30% sucrose before sectioning on a freezing-sliding microtome to obtain 50-μm-thick coronal sections. Immunohistochemical processing was performed using free-floating sections and immunoperoxidase methods. Sections were treated with hydrogen peroxide, washed in Tris buffer, blocked with normal serum, and incubated with anti-LR11 C-terminal antibody, the specificity of which has already been established (25). On day 2, sections were incubated with biotinylated secondary antibody followed by avidin–biotin–peroxidase complex for 1 hour at 4°C (Vector Elite ABC kit; Vector Laboratories, Burlingame, CA). Immunoreactivity was visualized with fluorescent-conjugated tyramide reagent (TSA Cyanine 3 System; PerkinElmer Life Sciences, Boston, MA). Mounted tissue sections were dehydrated briefly, hydrated, then submerged in 1% thioflavine-S solution for 8 minutes, and rinsed in 80% ethanol. Confocal images were captured on a Zeiss LSM510 microscope.
Immunoblotting was performed according to standard procedures. Protein concentrations were measured with a protein assay kit (BCA; Pierce, Rockford, IL). Samples were solubilized in Laemmli sample buffer, separated on 7.5% SDS-polyacrylamide gels, and transferred electrophoretically to PVDF membranes (Immobilon-P; Millipore, Billerica, MA). Blots were blocked for 1 hour at room temperature and probed with either a monoclonal LR11 primary antibody (26) or polyclonal LR11 C-terminal antibody. Loading consistency was established with a monoclonal elongation factor-1α (EF1-α) antibody (Upstate Cell Signaling Solutions, Charlottesville, VA) (27) or a monoclonal actin antibody (Abcam, Cambridge, MA) (28). Sections were then incubated with fluorophore-conjugated goat anti-mouse and goat anti-rabbit secondary antibodies (Molecular Probes, Eugene, OR) at room temperature for 1 hour. Images were captured and band intensities quantified using an Odyssey Image Station (LiCor, Lincoln, NE).
Paraffin sections of cognitively normal controls, sporadic AD, and FAD subjects from the Emory University ADRC, University of Washington ADRC, and Drexel University brain banks were used in this study. Specifically, there were 11 control 868 cases from individuals who had been identified as cognitively normal and free of AD-related neuropathology, 17 sporadic AD cases, and 14 FAD cases (9 PS1 cases and 5 PS2 cases; see Table for details). Blocks of frontal cortex were fixed for 24 to 48 hours in 4% paraformaldehyde or for 2 weeks in 10% neutral-buffered formalin and then embedded in paraffin. Paraffin-embedded blocks were cut into 8-μm sections, deparaffinized, and pretreated with pepsin (Biomeda, Foster City, CA). Sections were incubated with a polyclonal LR11 C-terminal primary and biotinylated goat anti-rabbit secondary antibodies as described previously. Immunoreactivity was visualized with 3,3-diaminobenzidine tetrahydrochloride (DAB). Sections were also counterstained with hematoxylin. Control sections incubated without primary antibody showed negligible staining.
A 5-point scale of immunostaining intensity was used to quantify LR11 expression levels with the following parameters: 1 = little to no staining; 2 = light staining; 3 = moderate staining; 4 = moderate to strong staining; and 5 = very strong staining. Scoring was conducted in blinded fashion by one observer.
To evaluate whether extensive amyloidosis can lead to a reduction in LR11 expression in vivo, we qualitatively and quantitatively assessed LR11 protein expression in 3-, 6-, 9-, and 18-month-old PS1/APP and wild-type littermate control mice. PS1/APP mice develop amyloid accumulation early and show evidence of thioflavine-S-positive plaques by 3 months of age. Amyloid burden increases progressively with age (Fig. 1A), and by 18 months of age, PS1/APP mice exhibit extensive plaque pathology similar that observed in human AD brain (Fig. 1B).
Immunohistochemical analysis of LR11 protein expression reveals similar LR11 immunoreactivity between PS1/APP mice and wild-type littermates, even in older mice that exhibit robust amyloidosis (Fig. 2). Quantitative Western blotting confirms that LR11 protein expression levels are not altered in PS1/APP mice compared with age-matched wild-type littermates (Fig. 3). The finding that LR11 expression is unaltered in a transgenic mouse model of aggressive amyloidosis is an important observation and supports the hypothesis that loss of LR11 protein expression in sporadic AD brain is not simply a byproduct of amyloid accumulation. However, these mice do not fully recapitulate the pathogenic cascade of AD. Most notably, transgenic PS1/APP mice do not exhibit tangle pathology or extensive neurodegeneration. Therefore, it was important to further assess LR11 expression in human tissue, specifically comparing sporadic AD and genetically based FAD variants.
To assess LR11 protein expression in cognitively normal, sporadic AD, and FAD tissue, we evaluated the intensity of LR11 immunoreactivity in frontal cortex of 42 individuals (Table). Gender and postmortem interval did not differ among the 3 groups (χ2 = 0.783, p = 0.676; analysis of variance [ANOVA], F = 0.244, df = 2,27, p = 0.785). Statistical analysis of age among groups was significantly different (ANOVA, F = 8.43, df = 3,37, p < 0.001), and a Bonferroni posttest found that the PS1 cases were younger than the sporadic AD group (t = 4.99, p < 0.001); however, there was no difference in age among the control, sporadic AD, and PS2 cases. Although control, sporadic AD, and FAD cases did not significantly vary with regard to the presence of the ApoE ε4 allele (χ2 = 4.379, p = 0.112), there was a higher frequency of ε4 allele presence in the sporadic AD group (8 of 16) compared with the control (3 of 11) and FAD groups (2 of 9), as expected. Fixation conditions varied somewhat among cases, which were either fixed for 2 weeks in formalin or for 24 to 48 hours in 4% paraformaldehyde; however, we observed no consistent trends in staining intensity scores between the formalin and paraformaldehyde-fixed tissue sections.
In control brains, LR11 expression is characterized by strong punctuate staining, especially obvious in larger pyramidal neurons in frontal cortex and hippocampus (Fig. 4). LR11 expression in neurons remains restricted to the somatodendritic compartment of the cells and is typically cytoplasmic, consistent with its known localization to endosomal compartments and Golgi membrane (22, 23). In contrast to the strong staining in controls, there is a striking loss of LR11 staining in frontal cortex of individuals with sporadic AD (8).
LR11 staining in frontal cortex from FAD, sporadic AD, and cognitively normal individuals revealed a different pattern of LR11 expression in individuals with FAD and individuals with sporadic AD (Fig. 4). On the 5-tiered scale used here, LR11 staining in control tissue was generally moderate (mean score = 3.2 [n = 11]), whereas staining in sporadic AD tissue typically fell into the light-staining group (mean score = 2.11 [n = 17]). The FAD staining mean was 3.14 (n = 14), corresponding to moderate staining intensity. A Kruskal-Wallis statistical analysis revealed a significant difference in staining intensity among the 3 experimental groups (Fig. 5; F = 12.13, p = 0.002). As expected, semi-quantitative scoring of LR11 immunointensity level showed reduced staining intensity in individuals with sporadic AD compared with control tissue (p < 0.05; Dunn multiple comparison test). Within the sporadic AD group, the presence of an ApoE ε4 allele did not affect LR11 staining intensity in this study (Mann-Whitney, F = 19.5, p = 0.19); however, we did observe a weak trend toward increased LR11 immunostaining intensity in ε4-negative compared with ε4-positive sporadic AD cases that may warrant future studies using larger cohorts.
In contrast to the sporadic AD cases, individuals carrying either PS1 or PS2 familial mutations showed no reduction in LR11 intensity compared with control tissue. Because LR11 staining intensity was not significantly different in the PS1 FAD variants compared with PS2 variants, these individuals were pooled for statistical analyses. LR11 staining intensity in FAD cases was significantly higher than that in sporadic AD tissue (p < 0.01, Dunn multiple comparison test).
In addition to LR11 immunostaining, quantitative immunoblotting was used to measure total protein levels in a representative subset of control (n = 5), sporadic AD (n = 6), and FAD (n = 8) cases for which frozen tissues were available (Fig. 6). Compared with controls, LR11 was decreased in sporadic AD cases by 30% (t = 2.165, df = 9, p = 0.058). Whereas the difference between LR11 expression levels in control (n = 5) and sporadic AD (n = 6) cases did not quite reach statistical significance in this small cohort, these results are consistent with our previous published findings, in which we found a 25% reduction in LR11 protein level (8). Conversely, LR11 protein level was unchanged in FAD frontal cortex compared with controls (t = 0.504, df = 10, p = 0.625). It is worth noting that the ages of control, sporadic AD, and PS2 cases were not significantly different. Therefore, the loss of LR11 seen in individuals with sporadic AD cannot simply be attributed to age-associated changes in brain. Extending the previous observation that LR11 expression is unchanged in PS1/APP transgenic mice, these results indicate that LR11 expression and distribution are unaltered in individuals carrying familial forms of AD.
Recently, we identified the striking loss of LR11 transcript and protein in brains of individuals with sporadic AD (8). Like with many biologic changes that occur as a consequence of the pathologic cascade in AD, this loss could simply be explained by downstream events associated with amyloidosis and neurodegeneration. However, we report here that in both a transgenic mouse model of amyloidosis and in brain tissue of individuals harboring similar genetic mutations that cause familial AD, there is no loss of LR11 protein expression. These results suggest that reduced expression of LR11 is not simply an effect of amyloid accumulation in sporadic AD brain.
Although neuropathologic features of FAD and sporadic AD are very similar, the trigger to pathogenesis is distinct. In the case of FAD, development of disease is directly linked to genetic mutations. Mutations in 3 genes, PS1, PS2, and APP, result in increased production of Aβ, particularly the longer Aβ1–42 species, by modifying the substrate (APP) or by modulating the activity of the γ-secretase enzyme that releases Aβ from full-length APP (3–7). Although amyloid accumulation is often considered a primary event in sporadic AD, the cause of increased amyloid production or deposition is unclear. This difference in underlying mechanism of disease may explain the marked difference in LR11 expression in FAD compared with sporadic AD.
Because the initial identification of APOE polymorphism and disease susceptibility, it has become increasingly clear that there is a strong association between cholesterol metabolism and amyloid accumulation (14, 29). Although the number of APOE ε4 allele carriers between our 3 experimental groups was not significantly different, we cannot rule out a modest effect of ApoE genotype on LR11 expression, particularly among sporadic AD cases. It is unclear if there is a differential effect of ApoE isoforms on the activity of LDL-Rs in the brain. The affinity of LR11 for different isoforms of ApoE has not been directly examined; however, low-density lipoprotein receptor family members, LDL-R, and the low-density lipoprotein receptor-related protein (LRP), have similar affinities for apoE3 and apoE4. Whether apoE3 and apoE4 can differentially influence LR11 expression and/or trafficking is an intriguing question for future studies.
In addition to APOE, a number of other genes involved in cholesterol transport and catabolism have been implicated as putative risk factors for sporadic AD, including LRP (30). Epidemiologic evidence has suggested protection from development of AD in individuals treated with drugs that lower cholesterol levels by inhibiting HMG CoA reductase, the rate-limiting enzyme in cholesterol synthesis (31, 32). A number of studies have shown that statin treatment in vitro and in vivo can regulate levels of Aβ (33, 34). It is also becoming clear that altered cholesterol trafficking can influence APP processing and Aβ production (14). For example, mutation of the Niemann-Pick protein (NPC1) is characterized by aberrant cholesterol storage in endosomal and lysosomal compartments and leads to elevated levels of Aβ as well as the formation of neurofibrillary tangles in brain (35–37).
Our results indicate that LR11 loss is specific to the more common sporadic form of AD and may represent a proximal component of the pathogenic cascade. We hypothesize that LR11 may protect against amyloidogenesis in brain. Therefore, loss of LR11, which is seen in sporadic AD, may exacerbate amyloidosis and potentiate early events in the disease process. Recent studies suggest that LR11 can interact with APP and BACE in Golgi and endosomal compartments and influence the trafficking and processing of APP (22, 23, 38). Increased LR11 expression in cell culture increases the colocalization of APP with endocytic markers and reduces the generation of Aβ. Mechanistically, LR11 may protect from amyloidogenesis by shuttling full-length APP through the degradative endosomal pathway and altering substrate–enzyme interactions between APP and its amyloidogenic enzymatic partners, BACE and γ-secretase. The search for molecules that play a primary role in amyloidosis is of great interest to medical science because a major goal of AD research is to identify therapeutic targets that may stem the onset and progression of disease. Pharmacologic treatments that can increase LR11 expression or function may prove to be an effective, novel therapeutic strategy.
The authors thank Veronica Walker, Howard D. Rees, and Stephanie Carter for excellent technical assistance.
This work was supported by NIH-NIA grants AG024214, AG025688, and AG05136.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Quick Look
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Property DetailsIn the city and the countryside, this sunny plot!The hillside location is suitable for the construction of a bungalow on the basement or a house. By allowable floor space, up to 750 m², you also have to build an apartment building that option.On the property a well already exists, and a variety of fruit trees, the property is completely fenced.Trees and shrubs give discretion. Another nice detail is a small stream that flows behind an adjacent bike path.A Beautiful Place for a new home!A plot of land which offers many possibilities of use and a lot of freedom for individuality because of Bebaungsplanes.Have we piqued your interest? Then please call us at any time, and together we can discuss the details.
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Additional Property InformationThis condo listing is located in Gladenbach. The property is presently selling at $110,000.
This property is listed by VON POLL IMMOBILIEN headquartered in Germany.


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Arrests netted following city Christmas parade
Karen Ann Nelson
Karen Ann Nelson, 59, of Elkins, passed away at Nella's Nursing Home in Elkins on Wednesday, Sept. 4, 2013, where she had been a resident since Jan. 7, 2003. She was born in Petersburg, on July 31, 1954, the daughter of the late Arthur Jacob "Jake" and Lillian (Moyers) Hevener. Karen married Wilbur Harold Nelson Jr., and he preceded her in death on Aug. 11, 2009.
Karen attended Pendleton County schools and Mt. Zion United Methodist Church and she had worked at Hanover Shoe in Franklin for 25 years. She loved photography and sending cards and letters to her friends and family.
Karen is survived by a sister, Katherine "Kitty" Hevener of Cincinnati, Ohio.
Mrs. Nelson's family will receive friends on Saturday, Sept. 7, 2013, from 10 to 11 a.m. at the Basagic Funeral Home in Franklin, with Pastor Roger Elza officiating funeral services at 11 a.m. Interment will be in Doe Hill Cemetery, Doe Hill, Va. Memorials may be made to Mt. Zion United Methodist Church or charity of choice. Memories and words of comfort may be left at www.basagic.com.


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Barbara Lloyd Redfern, 86, of West Caldwell, died on Saturday, Oct. 20,2001 at Mountainside Hospital in Montclair. Born in New Market, Va., Mrs. Redfern lived in Fredericksburg, Va., before moving to West Caldwell. She worked in retail stores and was a member of the Veterans of Foreign Wars Ladies Auxiliary, Spotsylvania, Va., Post 10546. Mrs. Redfern is survived by her daughter, Deborah R. Noblin of Spotsylvania, Va.; her son, Paul W. Redfern of West Caldwell; her sisters, Anna Mary Blosser of New Market, Va., Lena Ellis of Pensacola, Fla., Frances Irvin of Columbia Furnace, Va., Matte Folkes of Penn Laird, Va., Alice Kennedy of Broadway, Va. and Nancy Whitmer of Wardenville, W.Va.; her eight grandchildren; her two great-grand children and numerous nieces and nephews.
A funeral service was held on Wednesday, Oct. 24, at the Mullins & Thompson Chapel in Fredericksburg, Va., and interment followed at Emmanuel Lutheran Church Cemetery in New Market Va.
Memorial donations may be made to the American Cancer Society, c/o Trudy Clifton , HC 76 Box 1527, 113 Tallpines Ave., Locust Grove, Va. 22508.


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Maddox - The Alphabet of Manliness
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