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1.  Breast-Cancer Risk in Families with Mutations in PALB2 
The New England journal of medicine  2014;371(6):497-506.
Germline loss-of-function mutations in PALB2 are known to confer a predisposition to breast cancer. However, the lifetime risk of breast cancer that is conferred by such mutations remains unknown.
We analyzed the risk of breast cancer among 362 members of 154 families who had deleterious truncating, splice, or deletion mutations in PALB2. The age-specific breast-cancer risk for mutation carriers was estimated with the use of a modified segregation-analysis approach that allowed for the effects of PALB2 genotype and residual familial aggregation.
The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% (95% confidence interval [CI], 9 to 20) by 50 years of age and 35% (95% CI, 26 to 46) by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort (P < 0.001) and by other familial factors (P = 0.04). The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25 to 44) for those with no family history of breast cancer to 58% (95% CI, 50 to 66) for those with two or more first-degree relatives with breast cancer at 50 years of age.
Loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect both to the frequency of cancer-predisposing mutations and to the risk associated with them. Our data suggest the breast-cancer risk for PALB2 mutation carriers may overlap with that for BRCA2 mutation carriers. (Funded by the European Research Council and others.)
PMCID: PMC4157599  PMID: 25099575
2.  Counting whales in a challenging, changing environment 
Scientific Reports  2014;4:4170.
Estimating abundance of Antarctic minke whales is central to the International Whaling Commission's conservation and management work and understanding impacts of climate change on polar marine ecosystems. Detecting abundance trends is problematic, in part because minke whales are frequently sighted within Antarctic sea ice where navigational safety concerns prevent ships from surveying. Using icebreaker-supported helicopters, we conducted aerial surveys across a gradient of ice conditions to estimate minke whale density in the Weddell Sea. The surveys revealed substantial numbers of whales inside the sea ice. The Antarctic summer sea ice is undergoing rapid regional change in annual extent, distribution, and length of ice-covered season. These trends, along with substantial interannual variability in ice conditions, affect the proportion of whales available to be counted by traditional shipboard surveys. The strong association between whales and the dynamic, changing sea ice requires reexamination of the power to detect trends in whale abundance or predict ecosystem responses to climate change.
PMCID: PMC3952195  PMID: 24622821
3.  Effects of enzyme replacement therapy on growth in patients with mucopolysaccharidosis type II 
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked, recessive, lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase. It has multisystemic involvement, with manifestations in the brain, upper respiratory tract, heart, abdomen, joints and bones. Bone involvement leads to decreased growth velocity and short stature in nearly all patients. A therapeutic option for patients with MPS II is enzyme replacement therapy (ERT) with idursulfase (Elaprase®). We compared annual growth rates before and during ERT in 18 patients from Mainz, Germany, and Manchester, UK. Group 1 included nine patients who started ERT before 10 years of age; group 2 contained nine patients aged more than 10 years at the start of ERT. All patients had received weekly or biweekly ERT or placebo for 1 year, followed by ERT for more than 3 years. For patients in group 1, the mean (± SD) height increase was 14.6 ± 5.5 cm during 3 years of ERT. Only one patient in this group (who was below the 3rd percentile when starting ERT) deviated from the normal growth curve over this time. Patients in group 2 had a mean height increase of 8.1 ± 1.7 cm after 3 years of ERT compared with an increase of 1 cm in the year before ERT. ERT seems to have a positive influence on growth in patients with MPS II. Most benefit is seen in patients beginning ERT before the age of 10 years. This supports the recommendation that ERT should be started as early as possible in patients with MPS II.
PMCID: PMC3026660  PMID: 20978944
4.  Subcortical infarction resulting in acquired stuttering 
Stuttering is an uncommon presentation of acute stroke. Reported cases have often been associated with left sided cortical lesions, aphasia, and difficulties with other non-linguistic tests of rhythmic motor control. Three patients with subcortical lesions resulting in stuttering are discussed. In one patient the ability to perform time estimations with a computerised repetitive time estimation task was characterised.
One patient had a pontine infarct with clinical evidence of cerebellar dysfunction. A second patient had a left basal ganglionic infarct and a disruption of timing estimation. A third patient had a left subcortical infarct and a mild aphasia.
These findings expand the reported distribution of infarction that can result in acquired stuttering. Subcortical mechanisms of speech control and timing may contribute to the pathophysiology of acquired stuttering.

PMCID: PMC1737123  PMID: 10990523
5.  Adolescent Obsessive-Compulsive Drinking Scale: an assessment tool for problem drinking. 
Alcoholism has been studied in adults and found to share obsessive-compulsive characteristics. The Yale-Brown Obsessive Compulsive Scale (YBOC) was used to quantify the measurements of this disorder. This study adapted the YBOC for use with adolescents/young adults in an attempt to measure the "craving" expressed as obsessive and compulsive phenomenon. The primary findings show that the obsessive compulsive dimensions of alcohol cravings, as described in adult populations, also exist in adolescent/young adults. The Adolescent Obsessive Compulsive Drinking Scale (A-OCDS) was developed utilizing idioms and language typical for the 17-20 age group. Various quantitative evaluations proved that the Interference and Irresistibility sub-scales were the primary dimensions causing the obsessive behavior. This study begins to address this aspect of adolescent substance abuse utilizing a tool that is easy to administer. Because of the ease of use, although not a diagnostic instrument, the A-OCDS may be useful for identifying problem drinking in adolescents as well as detecting impairment in function related to drinking.
PMCID: PMC2593946  PMID: 12656441
6.  Prospective care of elderly patients in family practice. Is screening effective? 
Canadian Family Physician  1998;44:2677-2687.
OBJECTIVE: To evaluate cost and benefits of screening for and treating health and lifestyle risks among community-dwelling elderly. DESIGN: Randomized controlled trial. SETTING: Primary care. PARTICIPANTS: An opportunistic and prompted sample of 619 rostered elderly patients presenting for treatment who screened positive. INTERVENTIONS: One third (209) of experimental subjects had screening questionnaires placed in their charts with concerns highlighted for referrals. Two control groups received usual care. MAIN OUTCOME MEASURES: Yearly assessments of health service use and multidimensional functional capacity. RESULTS: Overall, screening and treatment of functionally active, elderly, middle-class people had no significant beneficial effect. Almost half of the experimental sample was ineligible because of treatment noncompliance. Generally ineligible subjects were older and more severely impaired. Subjects 75 years and older with risk factors showed improvement in daily living activities, and those living alone were found to have improved mental health and social functions (11% and 22%, respectively). CONCLUSIONS: Screening and treatment was ineffective in improving total functional capacity of all seniors 65 years and older. Elderly people 75 years and older, however, who were living alone or lonely did benefit from screening and treatment showing an improvement in daily activities, mental health scores, and social functions. This finding has implications for selective preventive health care spending for the elderly. A 2-year follow-up period could be too brief to detect long-term effects of early intervention with younger, middle-class seniors, especially those who are already functionally active.
PMCID: PMC2277795  PMID: 9870121
7.  Oregon reaffirms assisted suicide. 
BMJ : British Medical Journal  1997;315(7118):1253.
PMCID: PMC2127783  PMID: 9390048
10.  US medicine marches slowly toward UK solution. 
BMJ : British Medical Journal  1997;314(7076):252.
PMCID: PMC2125752  PMID: 9022486
11.  Primary care in the United States. 
BMJ : British Medical Journal  1996;313(7063):955-956.
PMCID: PMC2352338  PMID: 8892403
13.  Jack Kevorkian: a medical hero. 
BMJ : British Medical Journal  1996;312(7044):1434.
PMCID: PMC2351178  PMID: 8664610
15.  Prospective care of elderly patients in family practice. Part 3: Prevalence of unrecognized treatable health concerns. 
Canadian Family Physician  1995;41:1695-1710.
OBJECTIVE: To determine the prevalence of recognized and unrecognized health concerns and risks in an elderly population. DESIGN: Questionnaire survey. SETTING: Institutional primary care practice in a small southern Ontario city. PATIENTS: Volunteer sample of all patients older than 65 years (N = 1385) who were registered with the practice; were not demented, unstable, or residing in institutions at the time of contact; consented to participate; and completed a questionnaire (n = 674). MAIN OUTCOME MEASURES: Self-reported health concerns and health risks, including compliance with periodic health examinations; patient-generated concerns; and medical, lifestyle, and psychosocial issues. RESULTS: Most (92%) patients had at least one health concern or risk; 83% of these had one or more unreported or unrecognized health concerns or risks. The proportion with at least one concern or risk did not differ by sex or by age group. Many but not all complied with periodic health examinations. Loneliness was a meaningful psychosocial problem. Many patients had unreported medical concerns; the proportion rose slightly with age. Seniors with more concerns visited more frequently. CONCLUSIONS: Although most seniors had health concerns or risks, on average, each patient had only one or two concerns. These concerns are not concentrated in any particular area. Although non-attenders have fewer concerns, many have risk factors for diseases likely to progress without preventive measures, such as influenza vaccine and screening procedures for hypertension and breast, cervical, and prostate cancer.
PMCID: PMC2146674  PMID: 8829580
16.  Specialists in the United States: what lessons? 
BMJ : British Medical Journal  1995;310(6981):724-727.
PMCID: PMC2549102  PMID: 7711543
17.  Medical marriages. 
BMJ : British Medical Journal  1994;309(6970):1673.
PMCID: PMC2542659  PMID: 7819978
21.  Influence of reduced concentration of L-glutamine on growth and viability of cells in monolayer, in spheroids, and in experimental tumours. 
British Journal of Cancer  1986;54(5):733-741.
L-Glutamine is a requirement for many cells in tissue culture, an intermediate in many metabolic pathways, and an alternative substrate to glucose for energy metabolism. These properties suggest that glutamine concentration might be a determinant of cell viability in tumours, especially in regions that are deficient in other metabolites. We have therefore studied the effects of glutamine depletion on single cells in culture, on spheroids and on experimental tumours. Absence of glutamine suppressed the growth rate of two cell lines, but cells cultured for up to 6 h in the absence of glutamine had no decrease in plating efficiency. There was little effect on growth of MGH-U1 (human bladder cancer) spheroids of varying the glutamine concentration in the range of 0.1 to 2 mM and spheroids exposed to these concentrations did not develop central necrosis. Lower concentration of glutamine suppressed the rate of spheroid growth, and spheroids did not grow in the absence of glutamine. Pseudomonas 7A glutaminase reduced the survival of cells in glutamine-free culture and prevented growth of spheroids. Glutaminase was injected into mice bearing experimental tumours to reduce blood levels of glutamine; some animals also received 15 Gy radiation to their tumours to assess the effects of glutamine levels on surviving nutrient-deprived (i.e. hypoxic) cells. Glutaminase had no effect on cell survival in the Lewis lung tumour or in MGH-U1 xenografts, with or without radiation; glutaminase caused dose-dependent growth delay of the KHT tumour, which was additive to that caused by radiation. The present results suggest that (i) short-term changes of glutamine concentration have small effects on cell viability; and (ii) depletion of glutamine levels in blood through the in vivo use of glutaminase is unlikely to produce major therapeutic effects against nutrient-deprived cells in solid tumours.
PMCID: PMC2001537  PMID: 3801270
23.  Lichen Nitidus 
PMCID: PMC2181196  PMID: 19993115

Results 1-23 (23)