Cordilleran Ice Sheet mass loss preceded climate reversals near the Pleistocene Termination.

The Cordilleran Ice Sheet (CIS) once covered an area comparable to that of Greenland. Previous geologic evidence and numerical models indicate that the ice sheet covered much of westernmost Canada as late as 12.5 thousand years ago (ka). New data indicate that substantial areas throughout westernmost Canada were ice free prior to 12.5 ka and some as early as 14.0 ka, with implications for climate dynamics and the timing of meltwater discharge to the Pacific and Arctic oceans. Early Bølling-Allerød warmth halved the mass of the CIS in as little as 500 years, causing 2.5 to 3.0 meters of sea-level rise. Dozens of cirque and valley glaciers, along with the southern margin of the CIS, advanced into recently deglaciated regions during the Bølling-Allerød and Younger Dryas.

Modeling the functional genomics of autism using human neurons.

Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD.

Is primary endocrine therapy effective in treating the elderly, unfit patient with breast cancer?

INTRODUCTION: Elderly patients with oestrogen receptor (ER)-positive breast cancer wishing to avoid surgery or those who are considered unsuitable for a general anaesthetic may be treated with primary endocrine therapy. We have reviewed all patients with ER-positive breast cancer who were initially treated with primary hormone therapy (PHT) at a district general hospital in south Wales and investigated their outcome in order to evaluate the appropriateness of this method of managing breast cancer. MATERIALS AND METHODS: All patients with breast cancer who were initially treated with PHT between January 2002 and December 2008 were identified from a single consultant's prospectively maintained database. For each patient the Charlson co-morbidity index was calculated to give an estimate of ten-year survival. Patients who had died during the study period were identified from hospital and cancer registries. RESULTS: A total of 83 cancers in 82 patients with a median age of 81 years (range: 62-93 years) were included. All cancers were ER-positive. Six patients (7%) had a greater than 50% chance of surviving ten years, calculated using the Charlson index. The median follow-up period was 24 months (range: 6-72 months). Twelve patients (15%) had disease progression while taking PHT. Twenty-three patients (28%) have died (median time from diagnosis to death of 10.5 months, range: 1-77 months). Two patients (2%) experienced disease progression within six months of starting PHT and the number of patients whose cancer progressed increased with increasing length of follow up. Fourteen patients (17%) eventually underwent a wide local excision under local anaesthetic. CONCLUSIONS: PHT can be considered an effective treatment in this elderly, unfit population with the aim of stopping disease progression so that these patients die with their breast cancer, not of it.

A review of needle core biopsy diagnosed radial scars in the Welsh Breast Screening Programme.

INTRODUCTION: Radial scars are benign breast lesions; their appearance on mammography may, however, mimic carcinoma. Needle core biopsy is performed for pre-operative diagnosis and, currently in Wales, all lesions with benign biopsy results are surgically excised. We have reviewed all cases of needle core biopsy-diagnosed radial scars from the Welsh breast screening programme, Breast Test Wales (BTW), and investigated the outcome of radial scars based on histology from surgical excision in order to evaluate the appropriateness of the current management of these lesions in Wales. PATIENTS AND METHODS: All needle core biopsy diagnosed radial scars were identified from the BTW screening database from the start of screening in 1989 until the end of 2007. RESULTS: A total of 118 patients were diagnosed with radial scars on needle core biopsy; two patients had bilateral radial scars. Median patient age was 54 years (range, 49-68 years). Ninety-five lesions (79%) were thought to be pure radial scars on needle core biopsy; however, only 81 pure radial scars were identified on excision biopsy histology. Carcinoma was present in seven patients and ductal carcinoma in situ in nine patients at excision biopsy. In two patients, the cancers occurred in lesions reported as pure radial scars on needle core biopsy. Twenty-two lesions showed atypical ductal or lobular hyperplasia (ADH/ALH) or both on excision biopsy; 14 of these lesions were classed as pure radial scars by needle core biopsy. CONCLUSIONS: All core biopsy diagnosed radial scars, presenting as screen detected abnormalities, should be excised due to their association with premalignant and malignant conditions.

Community Case Management improves Use of Treatment for Childhood Diarrhea; Malaria and Pneumonia in a Remote District of Ethiopia

Background: Ethiopia's Health Extension Workers (HEW) deliver preventive interventions and treat childhood diarrhea and malaria; but not pneumonia. Most of Ethiopia's annual estimated 4 million childhood pneumonia cases go untreated. Objective: Evaluate the performance of volunteers in providing Community Case Management (CCM) for diarrhea; fever and pneumonia - in a pre-HEW setting in Liben Woreda; Oromiya Regional State. Methods: Save the Children supported Ministry of Health and communities to deliver child survival interventions from 1997-2006. We obtained permission in 2005 to train 45 volunteers from remote kebeles in CCM. We evaluated the strategy through reviewing registers and supervision records; examining CCM workers; focus group discussions; and three household surveys. Results: The CCM workers treated 4787 cases; mainly: malaria (36); pneumonia (26); conjunctivitis (14); and watery diarrhea with some dehydration (12). They saw 2.5 times more cases of childhood fever; pneumonia; and diarrhea than all the woreda's health facility staff combined. Quality of care was good. Conclusion: The availability; quality; demand; and use of CCM were high. These CCM workers were less educated and less trained than HEWs who perform complicated tasks (Rapid Diagnostic Tests) and dispense expensive antimalarial drugs like Coartemr. They should also treat pneumonia with inexpensive drugs like cotrimoxazole to help achieve Millennium Development Goal 4

Is general practitioner access to breast imaging safe?

AIM: The aim of this study was to assess the consultant radiologist run open-access breast radiology service (OAR) to investigate whether the system was safe or whether cancers were being missed. METHODS: A retrospective review of the national cancer registry database to identify patients presenting with symptomatic breast cancer in the catchment area of the Royal Glamorgan Hospital (RGH) from April 2000 to April 2002 was performed. Pathology, radiology and outpatient records were reviewed to identify patients previously assessed at the RGH. RESULTS: Fifty-four patients with breast cancer were diagnosed via the OAR and 159 by the breast clinic (BC). Twelve patients with breast cancer were diagnosed after their initial presentation. Eight patients had been previously seen for benign breast lesions. Four patients had missed breast cancers (two were initially seen via the BC and two via the OAR). A significant difference in the number of cancers missed by the two referral routes was not observed (p = 0.221). CONCLUSION: OAR is as accurate a means of diagnosing breast cancer as traditional rapid access BCs. Women presenting with discrete lumps with no radiological abnormality should still undergo assessment with clinical fine core-biopsy.

Two-view mammography at the incident round has improved the rate of screen-detected breast cancer in Wales.

AIM: To investigate whether pre-invasive and invasive cancer detection rates were improved in Wales after the introduction of two views at incident screens. METHODS: The records of women attending follow-up screening for 2 years before and 2 years after the introduction of two-view incident screening were analysed. Cancer detection rates were compared before and after introduction of two view screening. RESULTS: At the incident round 98,752 women had one and 95,464 had two views. Five hundred and fifty-five cancers were detected with one view and 744 with two, an increased detection rate from 5.6 to 7.8 cancers per 1000 women screened (p=0.01). Two hundred and thirty-nine small cancers were detected with one view and 323 with two, increasing the detection rate from 2.4 to 3.4 per 1000 women screened (p=0.05). CONCLUSIONS: Two-view mammography at incident rounds detects more cancers and more favourable prognosis small cancers than single-view mammograms.

Patient demographics and treatment for early breast cancer: an observational study.

This study aims to examine relationships between demographic factors and treatment choice for early breast cancer (T2/N<1). Two hundred and two patients were offered modified radical mastectomy (MRM), breast conserving therapy (BCT) or MRM and reconstruction and interviewed at a University Hospital and oncology centre in South Wales. Median age at treatment was 57 (32-90) years. Seventy-one patients (35%) choose MRM, 10 (5%) MRM and reconstruction and 121 (60%) BCT. Median age of women choosing MRM was 61 and 55 for BC (P<0.0001). Single women (P=0.009) and those with no family history of breast cancer (P=0.02) were more likely to choose MRM. There was no difference between treatment choice and method of cancer detection and the age at which the patient left education (P=0.065). Mean histological tumour diameter was smaller for women choosing BC (15 mm) than for women choosing mastectomy (17 mm; P=0.014). There was no association between tumour grade and treatment choice.

Quality of clinical case note entries: how good are we at achieving set standards?

INTRODUCTION: High quality entries in case notes are becoming increasingly important. Standards exist on what information entries should contain. We have compared case notes from surgical teams at the Royal Glamorgan Hospital with standards based on guidelines from The Royal College of Surgeons of England. PATIENTS AND METHODS: A total of 120 case notes, randomly selected from the department of general surgery, were reviewed. RESULTS: An 80% compliance was achieved in 25/35 standards and 100% was achieved in 6 (patient's name, date, surgeon's name and type of operation on the operation sheet and consent form signed and dated). The following fell short of 80% compliance: PAS number on every page (75%); entries timed (27%); and clinician's name (16%) and designation (27%) printed. Social history was only recorded in 73% of clerkings and family history in 33%. Results of laboratory tests were signed in 65% of notes and radiological tests were signed in 41%. CONCLUSIONS: Healthcare professionals need to be aware of, and comply with, standards. House officers should be given information about standards at departmental induction or during medical training.

Evidence-based guidelines for teaching patient-centered interviewing.

In a rare study of effectiveness of an interviewing method, we previously reported a randomized controlled trial demonstrating that training in a step-by-step patient-centered interviewing method improved residents' knowledge, attitudes, and skills and had a consistently positive effect on trained residents' patients. For those who wish to use this evidence-based patient-centered method as a template for their own teaching, we describe here for the first time our training program--and propose that the training can be adapted for students, physicians, nurse practitioners, physician assistants, and other new learners as well. Training was skills-oriented and experiential, fostered positive attitudes towards patient-centered interviewing, and used a learner-centered approach which paid special attention to the teacher-resident relationship and to the resident's self-awareness. Skills training was guided by a newly identified patient-centered interviewing method that described the step-by-step use of specific behaviors.

The Comprehensive Osteopathic Medical Licensing Examination, COMLEX-USA: a new paradigm in testing and evaluation.

Medical licensure in the United States demands a dynamic and current means to evaluate the competency of physicians seeking to practice medicine. A systematic measuring tool is required--one that is based on actual patient encounters and how physicians should apply their knowledge and skills to the clinical setting according to their level of training and professional development. Osteopathic physicians have a distinctive approach to healthcare, applying the biopsychosocial model with emphasis on the neuromusculoskeletal system. A component of this distinctive approach is a high level of knowledge and skill in the application of osteopathic manipulative treatment. Developed by the National Board of Osteopathic Medical Examiners, COMPLEX-USA is the new sequential three-level examination process for osteopathic medical licensure in the United States. The examination process is interdisciplinary and highly clinical, with even basic science components tested within a clinical context. Examination content is based on wide expert consensus and data consistent with osteopathic medical education, training, and practice. Its design is a novel multidimensional structure that emphasizes clinical problem-solving skills and osteopathic principles and practice within the context of life cycle, gender, ethnicity, and points of service. Design schemata and blueprints are included along with descriptions of strategic research and development. COMPLEX-USA represents the most appropriate pathway for initial licensure for a distinctive and unique professional: the osteopathic physician in the United States.

The effectiveness of intensive training for residents in interviewing. A randomized, controlled study.

BACKGROUND: Interviewing and the physician-patient relationship are crucial elements of medical care, but residencies provide little formal instruction in these areas. OBJECTIVE: To determine the effects of a training program in interviewing on 1) residents' attitudes toward and skills in interviewing and 2) patients' physical and psychosocial well-being and satisfaction with care. DESIGN: Randomized, controlled study. SETTING: Two university-based primary care residencies. PARTICIPANTS: 63 primary care residents in postgraduate year 1. INTERVENTION: A 1-month, full-time rotation in interviewing and related psychosocial topics. MEASUREMENTS: Residents and their patients were assessed before and after the 1-month rotation. Questionnaires were used to assess residents' commitment to interviewing and psychosocial medicine, estimate of the importance of such care, and confidence in their ability to provide such care. Knowledge of interviewing and psychosocial medicine was assessed with a multiple-choice test. Audiotaped interviews with real patients and videotaped interviews with simulated patients were rated for specific interviewing behaviors. Patients' anxiety, depression, and social dysfunction; role limitations; somatic symptom status; and levels of satisfaction with medical visits were assessed by questionnaires and telephone interviews. RESULTS: Trained residents were superior to untrained residents in knowledge (difference in adjusted post-test mean scores, 15.7% [95% CI, 11% to 20%]); attitudes, such as confidence in psychological sensitivity (difference, 0.61 points on a 7-point scale [CI, 0.32 to 0.91 points]); somatization management (difference, 0.99 points [CI, 0.64 to 1.35 points]); interviewing of real patients (difference, 1.39 points on an 11-point scale [CI, 0.32 to 2.45 points]); and interviewing (data gathering) of simulated patients (difference, 2.67 points [CI, 1.77 to 3.56 points]). Mean differences between the study groups were consistently in the appropriate direction for patient satisfaction and patient well-being, but effect sizes were too small to be considered meaningful. CONCLUSION: An intensive 1-month training rotation in interviewing improved residents' knowledge about, attitudes toward, and skills in interviewing.

New horizons in military dental laboratory training.

Dental laboratory training has taken on a new look for the military. As a result of numerous cost analyses Air Force, Navy, and Army training has been combined under one roof. All three services have molded their courses together to form a tri-service training program at Sheppard AFB in Wichita Falls, Texas. Graduation of the first class occurred on June 24, 1998. A 6 month basic course, as well as several advanced concept courses are offered by the program. Instructors from all branches of service are represented on staff to teach. The facility is state of the art and was built in 1991 to provide for Air Force Dental Training. Downsizing of today's military has resulted in dental training coming together to provide one quality course to military individuals qualified to enroll, thus ensuring tomorrow's laboratory technicians will be as qualified as those in the past.

A strategy for improving patient satisfaction by the intensive training of residents in psychosocial medicine: a controlled, randomized study.

PURPOSE: To use a controlled, randomized design to assess the effect on patient satisfaction of an intensive psychosocial training program for residents. METHOD: Twenty-six first-year residents, in two internal medicine and family practice community-based programs affiliated with the Michigan State University College of Human Medicine, were randomly assigned during 1991 and 1992 to a control group or a one-month intensive training program. Experiential teaching focused on many psychosocial skills required in primary care. A 29-item questionnaire administered before and after the residents' training evaluated their patients' satisfaction regarding patient disclosure, physician empathy, confidence in physician, general satisfaction, and comparison of the physician with other physicians. Analyses of covariance with groups and gender as factors and pre-training patient satisfaction scores as the covariate evaluated the effect of the training. RESULTS: The patients of the trained residents expressed more confidence in their physicians (p = .01) and more general satisfaction (p = .02) than did the patients of controls. The effect of training on patient satisfaction with patient disclosure (p < .01) and physician empathy (p < .05) was greater for female than for male residents. CONCLUSION: The intensive psychosocial training program for residents improved their patients' satisfaction.

Improving residents' confidence in using psychosocial skills.

OBJECTIVE: To evaluate an intensive training program's effects on residents' confidence in their ability in, anticipation of positive outcomes from, and personal commitment to psychosocial behaviors. DESIGN: Controlled randomized study. SETTING: A university- and community-based primary care residency training program. PARTICIPANTS: 26 first-year residents in internal medicine and family practice. INTERVENTION: The residents were randomly assigned to a control group or to one-month intensive training centered on psychosocial skills needed in primary care. MEASUREMENTS: Questionnaires measuring knowledge of psychosocial medicine, and self-confidence in, anticipation of positive outcomes from, and personal commitment to five skill areas: psychological sensitivity, emotional sensitivity, management of somatization, and directive and nondirective facilitation of patient communication. RESULTS: The trained residents expressed higher self-confidence in all five areas of psychosocial skill (p < 0.03 for all tests), anticipated more positive outcomes for emotional sensitivity (p = 0.05), managing somatization (p = 0.03), and nondirectively facilitating patient communication (p = 0.02), and were more strongly committed to being emotionally sensitive (p = 0.055) and managing somatization (p = 0.056), compared with the untrained residents. The trained residents also evidenced more knowledge of psychosocial medicine than did the untrained residents (p < 0.001). CONCLUSIONS: Intensive psychosocial training improves residents' self-confidence in their ability regarding key psychosocial behaviors and increases their knowledge of psychosocial medicine. Training also increases anticipation of positive outcomes from and personal commitment to some, but not all, psychosocial skills.

Studies of the structure and binding properties of hamster female protein.

We report here the characterization of hamster female protein (FP), a member of the pentraxin family of plasma proteins, as a molecule composed of glycosylated subunits of 25,655 MW containing a single intrachain disulphide bridge. In the presence of EDTA the subunits are non-covalently associated as pentamers of mass approximately 128,000 MW, and in the presence of calcium they aggregate further, probably to form decamers. This pentamer-decamer transition at physiological ionic strength has not been described in other pentraxins. As previously reported, FP shares the capacity of C-reactive protein (CRP) in other species to bind phosphocholine and we show here that it also resembles human CRP in binding only weakly to agarose, to human AA amyloid fibrils in vitro, and to mouse AA amyloid deposits in vivo. It thus differs markedly from human and mouse serum amyloid P component (SAP) but it is nevertheless deposited in hamster AA amyloid in vivo and clearly is the hamster counterpart of SAP in other species. These results illustrate the subtle diversity among members of the otherwise conserved pentraxin family of vertebrate plasma proteins.

Efficacy of a one-month training block in psychosocial medicine for residents: a controlled study.

STUDY OBJECTIVE: To determine the efficacy of a comprehensive, one-month psychosocial training program for first-year medical residents. DESIGN: Nonrandomized, controlled study with immediate pre/post evaluation. Limited evaluation of some residents was also conducted an average of 15 months after teaching. SETTING: Community-based, primary care-oriented residency program at Michigan State University (MSU). SUBJECTS: All 28 interns from the single-track MSU residency program during 1986/87-88/89 participated in this required rotation; there was no dropout or instance of noncompliance with the study. In the follow-up study in 1989, all 13 available trainees participated. Of 20 untrained, volunteer controls, ten were second/third-year residents in the same program during 1986/87 and ten were interns from a similar MSU program in Kalamazoo, MI, during 1988/89. TEACHING INTERVENTION: An experiential, skill-oriented, and learner-centered rotation with competency-based objects focused on communication and relationship-building skills and on the diagnosis and management of psychologically disturbed medical patients. MEASUREMENTS AND MAIN RESULTS: The two subsets of the control group were combined because residents and training programs were similar and because means and standard deviations for the subsets were similar on all measures. By two-way analyses of variance (group x gender), the trainee group showed significantly greater gains (p less than 0.001) on questionnaires addressing knowledge, self-assessment, and attitudes; a mean of 15 months following training, there was no significant deterioration of attitude scores. All trainees were also able to identify previously unrecognized, potentially deleterious personal responses using a systematic rating procedure. Residents' acceptance of the program was high. CONCLUSIONS: Intensive, comprehensive psychosocial training was well accepted by residents. It improved their knowledge, self-awareness, self-assessment, and attitudes, the latter improvement persisting well beyond training.