Drought timing and local climate determine the sensitivity of eastern temperate forests to drought.

Projected changes in temperature and drought regime are likely to reduce carbon (C) storage in forests, thereby amplifying rates of climate change. While such reductions are often presumed to be greatest in semi-arid forests that experience widespread tree mortality, the consequences of drought may also be important in temperate mesic forests of Eastern North America (ENA) if tree growth is significantly curtailed by drought. Investigations of the environmental conditions that determine drought sensitivity are critically needed to accurately predict ecosystem feedbacks to climate change. We matched site factors with the growth responses to drought of 10,753 trees across mesic forests of ENA, representing 24 species and 346 stands, to determine the broad-scale drivers of drought sensitivity for the dominant trees in ENA. Here we show that two factors-the timing of drought, and the atmospheric demand for water (i.e., local potential evapotranspiration; PET)-are stronger drivers of drought sensitivity than soil and stand characteristics. Drought-induced reductions in tree growth were greatest when the droughts occurred during early-season peaks in radial growth, especially for trees growing in the warmest, driest regions (i.e., highest PET). Further, mean species trait values (rooting depth and ψ50 ) were poor predictors of drought sensitivity, as intraspecific variation in sensitivity was equal to or greater than interspecific variation in 17 of 24 species. From a general circulation model ensemble, we find that future increases in early-season PET may exacerbate these effects, and potentially offset gains in C uptake and storage in ENA owing to other global change factors.

Inter- and intraobserver agreement in detection of testicular microlithiasis with ultrasonography.

BACKGROUND: Ultrasonography of the testis is a well-established diagnostic tool in detection of testicular microlithiasis (TML). Operator-dependent diagnostic variation related to skill, knowledge, and operator consistency are factors that influence detection of TML. PURPOSE: To determine inter- and intraobserver agreement for detection of TML using ultrasonography for a group of physicians with no or limited experience compared to a group of experience senior radiologists. MATERIAL AND METHODS: Between May and September 2014 a total of six observers evaluated 34 patients scrotal ultrasonography recorded from September to December 2013. The observers were blinded to patient history and previous ultrasonography. Three of the observers had no or limited experience with detection of TML, and three of the observers had more than 15 years of experience. Each observer reviewed all the scrotal ultrasonography recordings twice with a time interval of 3 months. RESULTS: The inter-observer agreement showed substantial agreement and up to almost perfect agreement (κ = 0.86). Both the experienced and less experienced observers had a higher agreement in detecting and grading TML in their second reading. CONCLUSION: The ultrasonography grading system of TML in this study showed to be reproducible, with an inter- and intraobserver agreement ranging between substantial agreement and up to almost perfect agreement with many years of experience not necessarily being essential.

Expression of green fluorescent protein in human foreskin fibroblasts for use in 2D and 3D culture models.

The availability of fibroblasts that express green fluorescent protein (GFP) would be of interest for the monitoring of cell growth, migration, contraction, and other processes within the fibroblast-populated collagen matrix and other culture systems. A plasmid lentiviral vector-GFP (pLV-GFP) was utilized for gene delivery to produce primary human foreskin fibroblasts (HFFs) that stably express GFP. Cell morphology, cell migration, and collagen contraction were compared between nontransduced HFFs and transduced GFP-HFFs; no differences were observed. Immunocytochemical staining showed no differences in cell morphology between nontransduced and GFP-HFFs in both two-dimensional and three-dimensional culture systems. Furthermore, there was no significant difference in cellular population growth within the collagen matrix populated with nontransduced vs. GFP-HFFs. Within the limits of our assays, we conclude that transduction of GFP into HFFs did not alter the observed properties of HFFs compared with nontransduced fibroblasts. The GFP-HFFs may represent a new tool for the convenient monitoring of living primary fibroblast processes in two-dimensional or three-dimensional culture.

Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in-vitro sensitivity testing: a phase 2, single-center, open-label, and non-comparative study.

BACKGROUND: Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method's feasibility and clinical outcome as applied to patients with no satisfactory treatment options. METHODS: In this phase 2, single-center, open-label, non-comparative study (ClinicalTrials.gov, register NCT03251612), we enrolled 90 patients with metastatic colorectal cancer following progression on or after standard therapy. Participants were 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and metastasis available for biopsy. Biopsies from the metastatic site were cultured using organoids model. Sensitivity testing was performed with a panel of drugs with proven activity in phase II or III trials. At the discretion of the investigator considering toxicity, the drug with the highest relative activity was offered. The primary endpoint was the proportion of patients alive without disease progression at two months per local assessment. RESULTS: Biopsies available from 82 to 90 patients were processed for cell culture, of which 44 successfully generated organoids with at least one treatment suggested. The precision cohort of 34 patients started treatment and the primary endpoint, progression-free survival (PFS) at two months was met in 17 patients (50%, 95% CI 32-68), exceeding the pre-defined level (14 of 45; 31%). The median PFS was 67 days (95% CI 51-108), and the median overall survival was 189 days (95% CI 103-277). CONCLUSIONS: Patient-derived organoids and in-vitro sensitivity testing were feasible in a cohort of metastatic colorectal cancer. The primary endpoint was met, as half of the patients were without progression at two months. Cancer patients may benefit from functional testing using tumor-derived organoids. TRIAL REGISTRATION: ClinicalTrials.gov, register NCT03251612.

Interobserver Reliability and the Sigmoid Takeoff-An Interobserver Study.

Background: Colorectal cancer is the second most common cancer worldwide. The sigmoid takeoff is the landmark where the colon sigmoid curves toward the sacrum viewed from sagittal magnetic resonance imaging (MRI). The purpose of this study was to assess interobserver variability in the assessment of the anal verge and anorectal junction in patients diagnosed with rectal cancer on magnetic resonance imaging (MRI). Materials and Methods: The rectal MRI examinations were performed using a 1.5- or 3.0-tesla unit using an anterior coil and a standard scan protocol. Two senior radiologists assessed MRI scans from patients under investigation for rectal cancer. The two observers assessed the anal verge and takeoff in cm independently. Difference in agreement between the observers were evaluated using intraclass correlation (ICC) and graphically by Bland-Altman plots. Results: The study population (n = 122) included 68 (55.7%) female and 54 (44.3%) male subjects. The overall median age was 69.5 years (range 39-95 years). There was perfect agreement between the two observers when defining rectal tumor above or below the takeoff landmark. The reliability of measuring the distance from the anal verge to the sigmoid takeoff was 0.712. Conclusion: Overall, the study found a moderate reliability in assessing the location of the sigmoid takeoff, with a low difference in the distance measuring, as well as a good consensus concerning the determination of tumors in relation to the sigmoid takeoff. Routine implementation of this information within the report seems reasonable.

CT and 3 Tesla MRI in the TN Staging of Colon Cancer: A Prospective, Blind Study.

(1) Background: Computer tomography (CT) scanning is currently the standard method for staging of colon cancer; however, the CT based preoperative local staging is far from optimal. The purpose of this study was to investigate the sensitivity and specificity of magnetic resonance imaging (MRI) compared to CT in the T- and N-staging of colon cancer. (2) Methods: Patients underwent a standard contrast-enhanced CT examination. For the abdominal MRI scan, a 3 Tesla unit was used, including diffusion weighted imaging (DWI). Experienced radiologists reported the CT and MRI scans blinded to each other and the endpoint of the pathological report. (3) Results: From 2018 to 2021, 134 patients received CT and MRI scans. CT identified 118 of the 134 tumors, whereas MRI identified all tumors. For discriminating between stage T3ab and T3cd, the sensitivity of CT was 51.1% and of MRI 80.0% (p = 0.02). CT and MRI showed a sensitivity of 21.4% and 46.4% in detecting pT4 tumors and a specificity of 79.0% and 85.0%, respectively. (4) Conclusion: Compared to CT, the sensitivity of MRI was statistically significantly higher in staging advanced T3cd and T4 tumors. MRI has the potential to be used in the treatment planning of colon cancer.

Physics-constrained, low-dimensional models for magnetohydrodynamics: First-principles and data-driven approaches.

Plasmas are highly nonlinear and multiscale, motivating a hierarchy of models to understand and describe their behavior. However, there is a scarcity of plasma models of lower fidelity than magnetohydrodynamics (MHD), although these reduced models hold promise for understanding key physical mechanisms, efficient computation, and real-time optimization and control. Galerkin models, obtained by projection of the MHD equations onto a truncated modal basis, and data-driven models, obtained by modern machine learning and system identification, can furnish this gap in the lower levels of the model hierarchy. This work develops a reduced-order modeling framework for compressible plasmas, leveraging decades of progress in projection-based and data-driven modeling of fluids. We begin by formalizing projection-based model reduction for nonlinear MHD systems. To avoid separate modal decompositions for the magnetic, velocity, and pressure fields, we introduce an energy inner product to synthesize all of the fields into a dimensionally consistent, reduced-order basis. Next, we obtain an analytic model by Galerkin projection of the Hall-MHD equations onto these modes. We illustrate how global conservation laws constrain the model parameters, revealing symmetries that can be enforced in data-driven models, directly connecting these models to the underlying physics. We demonstrate the effectiveness of this approach on data from high-fidelity numerical simulations of a three-dimensional spheromak experiment. This manuscript builds a bridge to the extensive Galerkin literature in fluid mechanics and facilitates future principled development of projection-based and data-driven models for plasmas.

Intraoperative neurophysiological monitoring during spine surgery: a review.

Spinal surgery involves a wide spectrum of procedures during which the spinal cord, nerve roots, and key blood vessels are frequently placed at risk for injury. Neuromonitoring provides an opportunity to assess the functional integrity of susceptible neural elements during surgery. The methodology of obtaining and interpreting data from various neuromonitoring modalities-such as somatosensory evoked potentials, motor evoked potentials, spontaneous electromyography, and triggered electromyography-is reviewed in this report. Also discussed are the major benefits and limitations of each modality, as well as the strength of each alone and in combination with other modalities, with regard to its sensitivity, specificity, and overall value as a diagnostic tool. Finally, key clinical recommendations for the interpretation and step-wise decision-making process for intervention are discussed. Multimodality neuromonitoring relies on the strengths of different types of neurophysiological modalities to maximize the diagnostic efficacy in regard to sensitivity and specificity in the detection of impending neural injury. Thorough knowledge of the benefits and limitations of each modality helps in optimizing the diagnostic value of intraoperative monitoring during spinal procedures. As many spinal surgeries continue to evolve along a pathway of minimal invasiveness, it is quite likely that the value of neuromonitoring will only continue to become more prominent.

Diagnostic yield and complications of transthoracic computed tomography-guided biopsies.

INTRODUCTION: The widespread use of computed tomography (CT) improves detection of pulmonary lesions, which are not only detected at an increased rate but also at a smaller size. CT-guided lung biopsies are now more frequently used than fluoroscopy-guided lung biopsies. The main aim of the present paper was to investigate the outcome and complications of the biopsies. METHODS: We retrospectively collected the results and information from 520 CT-guided thorax biopsies. All biopsies were performed with CT-guided "beam-through" technique, using a 64-slice CT scanner. RESULTS: In 86% of the biopsies, the tissue material was found to be sufficient. In 32% of the biopsies, a complication arose, mostly pneumothorax (30%), but chest drainage was needed in only 15% of the 520 cases. Patients with more than ten cigarette pack-years had a complication risk that was twice as high at that of patients with fewer pack-years. We found that the risk of pneumothorax increased the further the lesion was from the skin surface, the smaller the lesions were and when the patient was biopsied in a lateral position. We also found a higher risk of complications in females than in males. CONCLUSIONS: CT-guided biopsy is an excellent tool for analysing pulmonary lesions. The present study clearly shows that the risk of developing a pneumothorax is significantly increased among smokers and former smokers with more than ten pack-years. FUNDING: none. TRIAL REGISTRATION: not relevant.

Development of a technology-based behavioral vaccine to prevent adolescent depression: A health system integration model.

Efforts to prevent depression have become a key health system priority. Currently, there is a high prevalence of depression among adolescents, and treatment has become costly due to the recurrence patterns of the illness, impairment among patients, and the complex factors needed for a treatment to be effective. Primary care may be the optimal location to identify those at risk by offering an Internet-based preventive intervention to reduce costs and improve outcomes. Few practical interventions have been developed. The models for Internet intervention development that have been put forward focus primarily on the Internet component rather than how the program fits within a broader context. This paper describes the conceptualization for developing technology based preventive models for primary care by integrating the components within a behavioral vaccine framework. CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral, Humanistic and Interpersonal Training) has been developed and successfully implemented within various health systems over a period of 14 years among adolescents and young adults aged 13-24.

Elastography and diffusion-weighted MRI in patients with rectal cancer.

OBJECTIVE: The current literature has described the usefulness of elastography and diffusion-weighted MRI in patients with cancer, but to the best of our knowledge so far none of them has compared the two new methods. The tumour cell density is related to the MRI-measured apparent diffusion-weighted coefficient (ADC). The purpose of the present study was to compare quantitative elastography based on ultrasound shear wave measurements with MRI ADC. METHODS: We prospectively examined 52 patients with histopathologically proven rectal cancer. The mean age was 67 years (range 42-90 years). Males: 39, females: 13. Tumour elasticity was measured transgluteally using the acoustic radiation force impulse (ARFI) to generate information on the mechanical properties of the tissue. The objective quantitative elastography shear wave velocity was blindly compared with the ADC measurements using a 1.5-T MRI system. RESULTS: The mean tumour elasticity was 3.05 m s(-1) [standard deviation (SD): 0.79], and the mean ADC was 0.69 × 10(-3) mm(2) s(-1) (SD: 0.27). Elasticity was inversely strongly correlated with ADC, r = -0.65 (Salkin scale). ARFI = 4.392 - 1.949 × ADC, R(2) = 0.43, p < 0.0001. Intercept = 4.392 (95% CI: 3.92 to 4.86), slope = -1.949 (95% CI: -1.31 to -2.59), p < 0.0001. CONCLUSION: Elasticity correlates with the estimated diffusion restriction by MRI ADC measurements in rectal tumours. The relationship between ARFI and ADC measurement was linear in our study population. ADVANCES IN KNOWLEDGE: This work describes a correlation between tissue elasticity and diffusion in rectal cancer.

Intrapleural staphylococcal superantigen induces resolution of malignant pleural effusions and a survival benefit in non-small cell lung cancer.

BACKGROUND: Malignant pleural effusion (MPE) may occur in up to 50% of patients with non-small cell lung cancer (NSCLC). The majority of these patients have a poor performance status and a dismal prognosis, with survival duration ranging from 2 to 3 months. Since these patients are typically symptomatic from their MPE, prompt treatment is required. Patients with symptomatic MPE from NSCLC and poor performance scores (Eastern Cooperative Oncology Group [ECOG] score >/= 2, Karnofsky performance status [KPS] score < 50) are generally not offered systemic chemotherapy. Treatment is palliative and includes intrapleural catheter drainage or chemical pleurodesis with talc, doxycycline, or bleomycin. None of the latter modalities prolong survival. OBJECTIVE: Our goal was to investigate the toxicity and therapeutic effect of a new therapeutic agent, Staphylococcus aureus superantigen (SSAg), a powerful T-cell stimulant administered intrapleurally to unselected, consecutive patients with MPE from NSCLC (stage IIIb with pleural effusion) and a poor performance status. By providing direct access of the SSAg to the bronchial and mediastinal lymphatics, we predicted that intrapleural administration of SSAg would induce resolution of MPE and prolong survival in this population with advanced NSCLC and a limited prognosis. METHODS: Fourteen consecutive, unselected patients with MPE from NSCLC and a median pretreatment KPS score of 40 (range, 10 to 60) received pleural instillation of SSAg, 100 to 400 pg, once or twice weekly (mean, 3.7 +/- 1.3 treatments [+/- SD]) until the pleural effusions resolved. They were evaluated for drug toxicity, resolution, duration of MPE, and survival. RESULTS: Other than mild fever (maximum grade 2), toxicity of SSAg treatment was trivial and notably devoid of respiratory distress or hypotension. Eleven patients had a complete response (CR), and 3 patients had a partial response of their MPE. In 12 patients, the response endured for > 90 days, with a median time to recurrence of 5 months (range, 3 to 23 months). The median survival for the SSAg-treated group was 7.9 months (range, 2 to 36 months; 95% confidence interval [CI], 5.9 to 11.4 months), compared to a median survival of 2.5 months (range, 0.1 to 57 months; 95% CI, 1.3 to 3.4 months) for 18 consecutive, unselected patients with MPE from NSCLC (stage IIIb) treated with talc poudrage (p = 0.044). Survival duration of all 14 SSAg-treated cases and 13 talc-poudrage-treated patients with comparable pretreatment KPS (range, 10 to 60; median, 40 and 30, respectively), and distribution (p = 0.5) was 7.9 months (95% CI, 5.9 to 11.4 months) and 2.0 months (95% CI, 0.4 to 2.9 months), respectively (p = 0.0023). Nine of 14 patients treated with SSAg survived > 6 months, 4 patients survived > 9 months, and 3 patients survived > 350 days. One of the patients in the CR group has survived 36 months. None of the 13 talc-treated patients survived > 6 months. INTERPRETATION: In 14 unselected, consecutive patients with MPE from NSCLC and poor pretreatment performance (median KPS of 40), the intrapleural administration of SSAg was efficacious in resolving the MPE without any clinically important adverse effects. SSAg-treated patients with a median KPS of 40 (range, 10 to 60) had a median survival that exceeded that with talc poudrage, and was comparable to current systemic chemotherapy used in patients with KPS >/= 70 status. SSAg treatment is simple to perform, minimally invasive, and does not require hospital time. It may be an attractive alternative to existing palliative modalities for stage IIIb patients with MPE and poor performance who are not candidates for systemic chemotherapy.

Transrectal ultrasound and magnetic resonance imaging measurement of extramural tumor spread in rectal cancer.

AIM: To evaluate the agreement between transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) in classification of ≥ T3 rectal tumors. METHODS: From January 2010 to January 2012, 86 consecutive patients with ≥ T3 tumors were included in this study. The mean age of the patients was 66.4 years (range: 26-91 years). The tumors were all ≥ T3 on TRUS. The sub-classification was defined by the penetration of the rectal wall: a: 0 to 1 mm; b: 1-5 mm; c: 6-15; d: > 15 mm. Early tumors as ab (≤ 5 mm) and advanced tumors as cd (> 5 mm). All patients underwent TRUS using a 6.5 MHz transrectal transducer. The MRI was performed with a 1.5 T Philips unit. The TRUS findings were blinded to the radiologist performing the interpretation of the MRI images and measuring the depth of extramural tumor spread. RESULTS: TRUS found 51 patients to have an early ≥ T3 tumors and 35 to have an advanced tumor, whereas MRI categorized 48 as early ≥ T3 tumors and 38 as advanced tumors. No patients with tumors classified as advanced by TRUS were found to be early on MRI. The kappa value in classifying early versus advanced T3 rectal tumors was 0.93 (95% CI: 0.85-1.00). We found a kappa value of 0.74 (95% CI: 0.63-0.86) for the total sub-classification between the two methods. The mean maximal tumor outgrowth measured by TRUS, 5.5 mm ± 5.63 mm and on MRI, 6.3 mm ± 6.18 mm, P = 0.004. In 19 of the 86 patients the following CT scan or surgery revealed distant metastases; of the 51 patients in the ultrasound ab group three (5.9%) had metastases, whereas 16 (45.7%) of 35 in the cd group harbored distant metastases, P = 0.00002. The odds ratio of having distant metastases in the ultrasound cd group compared to the ab group was 13.5 (95% CI: 3.5-51.6), P = 0.00002. The mean maximal ultrasound measured outgrowth was 4.3 mm (95% CI: 3.2-5.5 mm) in patients without distant metastases, while the mean maximal outgrowth was 9.5 mm (95% CI: 6.2-12.8 mm) in the patients with metastases, P = 0.00004. Using the MRI classification three (6.3%) of 48 in the MRI ab group had distant metastases, while 16 (42.1%) of the 38 in the MRI cd group, P = 0.00004. The MRI odds ratio was 10.9 (95% CI: 2.9-41.4), P = 0.00008. The mean maximal MRI measured outgrowth was 4.9 mm (95% CI: 3.7-6.1 mm) in patients without distant metastases, while the mean maximal outgrowth was 11.5 mm (95% CI: 7.8-15.2 mm) in the patients with metastases, P = 0.000006. CONCLUSION: There is good agreement between TRUS and MRI in the pretreatment sub-classification of ≥ T3 tumors. Distant metastases are more frequent in the advanced group.

Interobserver and intermodality agreement for detection of small bowel Crohn's disease with MR enterography and CT enterography.

BACKGROUND: Magnetic resonance enterography (MRE) and computed tomography enterography (CTE) visualizes small bowel Crohn's disease (CD) and its complications with high accuracy. The aim of this study was to determine the interobserver and intermodality agreement for detection of small bowel CD. METHODS: Fifty patients with suspected or known CD were included in the study and all patients underwent MRE and CTE on the same day. Four radiologists with experience in MRE and CTE techniques participated. Observers were blind to patient histories, results of ileocolonoscopies, and other small bowel examinations. Readers assessed the image quality, the presence of small bowel CD, and seven findings consistent with CD. RESULTS: The image quality was better with CTE than MRE (P < 0.001) but the diagnostic yields were comparable (P = 0.4). For detection of small bowel CD, the interobserver agreement was substantial in CTE (κ = 0.64) and moderate in MRE (κ = 0.48). The intermodality agreement was fair to substantial (κ = 0.40-0.64) for different observers. Two abscesses were detected and confirmed at subsequent surgery. One abscess was not detected with MRE and only recorded by two observers in CTE. A total of 10 fistulas were detected: three were confirmed at subsequent surgery and four were false-positive findings. CONCLUSIONS: MRE and CTE have comparable diagnostic yields in patients with suspected or known CD. However, CTE provides better image quality and interobserver agreement. In a substantial number of patients the diagnosis of small bowel CD is observer- and modality-dependent.

Operative strategies for minimizing hearing loss and other major complications associated with microvascular decompression for trigeminal neuralgia.

OBJECTIVE: To retrospectively assess the surgical outcomes and complication rates following microvascular decompression (MVD) for trigeminal neuralgia, using a targeted, restricted retrosigmoid approach. METHODS: During the period 1994-2009, a total of 119 patients underwent MVD for trigeminal neuralgia. A retrospective review was conducted in order to assess pain outcomes following surgery and at most recent follow-up. The intraoperative findings, Barrow Neurologic Institute (BNI) pain scores, medication usage, brainstem auditory evoked potential records, and complication rates (including postoperative hearing status) were reviewed and subsequently analyzed. RESULTS: Of the 119 patients who underwent MVD, 61 (51%) were male and 58 (49%) were female. The mean age was 60 years (range 22-86 years). Operative findings included 94 patients (79%) with arterial compression, 16 patients (13%) with isolated venous compression, 1 patient (1%) with a small arteriovenous malformation, and 8 patients (7%) with no obvious source of compression. No perioperative deaths or major complications, including hearing loss, occurred in any patients. Minor complications occurred in 9 patients (8%), including a transient trochlear nerve palsy in 1 patient, transient nystagmus in 1 patient, cerebrospinal fluid leak requiring revision in 1 patient, wound infections requiring revision in 3 patients, and wound infections requiring antibiotics alone in 3 patients. Follow-up data were available for 109 patients, of whom 88 (81%) had excellent outcomes (BNI Score I-II). Ninety-eight patients (90%) had good outcomes (BNI scores I-IIIb), 7 patients (6%) had persistent pain that was not controlled with medications (BNI Score IV), and 4 patients (4%) experienced no relief following surgery (BNI Score V). CONCLUSION: The use of a small craniectomy (<20 mm) in conjunction with a restricted retrosigmoid approach, inferolateral cerebellar retraction, and maintenance of the vestibular nerve arachnoid may minimize complications and optimize surgical outcomes associated with microvascular decompression for trigeminal neuralgia.

Multiple primary melanomas in a CDKN2A mutation carrier exposed to ionizing radiation.

BACKGROUND: Recent research has shown a possible causal relationship between ionizing radiation exposure and melanoma. Individuals with mutations in CDKN2A (cyclin-dependent kinase inhibitor 2A), the major melanoma predisposition gene, have an increased susceptibility to melanoma-promoting exposures, such as UV light. We describe a patient from a familial melanoma pedigree with 7 primary melanomas on the right side of her body, the first occurring 5 years after exposure to atmospheric nuclear bomb testing in the 1950s. OBSERVATIONS: Physical examination revealed phototype I skin, red hair, and 26 nevi (14 on the right and 12 on the left side of her body). One nevus was larger than 5 mm, and 2 were clinically atypical. Sequence analysis demonstrated a known deleterious mutation in CDKN2A (G-34T) and homozygosity for a red hair color variant in MC1R (melanocortin 1 receptor) (R151C). Fluorescence in situ hybridization analysis of blood, fibroblasts, and melanocytes from both upper extremities ruled out mosaicism. CONCLUSIONS: Individuals such as this patient, who has CDKN2A and MC1R mutations, are likely to be more susceptible to environmental insults. A careful review of environmental exposures in these vulnerable cases may reveal cancer-promoting agents, such as ionizing radiation, that go unnoticed in less susceptible populations.

'Like Minds, Like Mine': a New Zealand project to counter the stigma and discrimination associated with mental illness.

OBJECTIVE: To demonstrate how mass media advertising and community education has been successfully used in New Zealand as part of a comprehensive public health project to reduce stigma and discrimination associated with mental illness. CONCLUSIONS: The involvement of people with experience of mental illness in the campaign has been critical to its success. Advertising involving the stories of well-known and famous people who have experienced mental illness has created significant interest, awareness and improved attitudes among the general public. Local community education and other follow-up activities have also contributed to this success.

Sequence analysis of the Washington/1964 strain of human parainfluenza virus type 1 (HPIV1) and recovery and characterization of wild-type recombinant HPIV1 produced by reverse genetics.

A complete consensus sequence was determined for the genomic RNA of human parainfluenza virus type 1 (HPIV1) strain Washington/20993/1964 (HPIV1 WASH/64), a clinical isolate that previously was shown to be virulent in adults. The sequence exhibited a high degree of relatedness to both Sendai virus, a PIV1 virus recovered from mice, and human PIV3 (HPIV3) with regard to cis-acting regulatory regions and protein-coding sequences. This consensus sequence was used to generate a full-length antigenomic cDNA and to recover a recombinant wild-type HPIV1 (rHPIV1). Interestingly, the rHPIV1 could be rescued from full-length antigenomic rHPIV1 cDNA using HPIV3 support plasmids, HPIV1 support plasmids, or a mixture thereof. The replication of rHPIV1 in vitro and in the respiratory tract of hamsters was similar to that of its biologically derived parent virus. The similar biological properties of rHPIV1 and HPIV1 WASH/64 in vitro and in vivo, together with the previous demonstration of the virulence of this specific isolate in humans, authenticates the rHPIV1 sequence as that of a wild-type virus. This rHPIV1 can now be used to study the biological properties of HPIV1 and as a substrate to introduce attenuating mutations for the generation of live-attenuated HPIV1 vaccine candidates.