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Tissue stem-progenitor cell frequency has been implicated in tumor risk and progression. Tissue-specific factors linking stem-progenitor cell frequency to cancer risk and progression remain ill defined. Using a genetically engineered mouse model that promotes integrin mechanosignaling with syngeneic manipulations, spheroid models, and patient-derived xenografts we determined that a stiff extracellular matrix and high integrin mechanosignaling increase stem-progenitor cell frequency to enhance breast tumor risk and progression. Studies revealed that high integrin-mechanosignaling expands breast epithelial stem-progenitor cell number by potentiating progesterone receptor-dependent RANK signaling. Consistently, we observed that the stiff breast tissue from women with high mammographic density, who exhibit an increased lifetime risk for breast cancer, also have elevated RANK signaling and a high frequency of stem-progenitor epithelial cells. The findings link tissue fibrosis and integrin mechanosignaling to stem-progenitor cell frequency and causally implicate hormone signaling in this phenotype. Accordingly, inhibiting RANK signaling could temper the tumor promoting impact of fibrosis on breast cancer and reduce the elevated breast cancer risk exhibited by women with high mammographic density.SummaryElevated mechano-signaling and matrix stiffness promote progesterone and RANK mediated expansion of mammary progenitors and breast cancer risk and progression.

Optoelectronic devices in the mid-infrared have attracted significant interest due to numerous potential applications in communications and sensing. Molecular beam epitaxial (MBE) growth of highly doped InAs has emerged as a promising “designer metal” platform for the plasmonic enhancement of mid-infrared devices. However, while typical plasmonic materials can be patterned to engineer strong localized resonances, the lack of lateral control in conventional MBE growth makes it challenging to create similar structures compatible with monolithically grown plasmonic InAs. To this end, we report the growth of highly doped InAs plasmonic ridges for the localized resonant enhancement of mid-IR emitters and absorbers. Furthermore, we demonstrate a method for regaining a planar surface above plasmonic corrugations, creating a pathway to epitaxially integrate these structures into active devices that leverage conventional growth and fabrication techniques.

Graphical abstract, Highlights • Abnormalities in cell nuclear morphology is a hallmark of cancer. • Changes in nuclear morphology are utilized by pathologists in tumor grading. • Heterogeneity in DCIS grade may influence invasive progression. • Current pathological assessment of DCIS does not incorporate heterogeneity. • I mage analysis is a supplemental tool for pathologists to quantitatively grade DCIS., Abnormalities in cell nuclear morphology are a hallmark of cancer. Histological assessment of cell nuclear morphology is frequently used by pathologists to grade ductal carcinoma in situ (DCIS). Objective methods that allow standardization and reproducibility of cell nuclear morphology assessment have potential to improve the criteria needed to predict DCIS progression and recurrence. Aggressive cancers are highly heterogeneous. We asked whether cell nuclear morphology heterogeneity could be incorporated into a metric to classify DCIS. We developed a nuclear heterogeneity image index to objectively, and quantitatively grade DCIS. A whole-tissue cell nuclear morphological analysis, that classified tumors by the worst ten percent in a duct-by-duct manner, identified nuclear size ranges associated with each DCIS grade. Digital image analysis further revealed increasing heterogeneity within ducts or between ducts in tissues of worsening DCIS grade. The findings illustrate how digital image analysis comprises a supplemental tool for pathologists to objectively classify DCIS and in the future, may provide a method to predict patient outcome through analysis of nuclear heterogeneity.

Women with aggressive DCIS are at high risk of progression to invasive breast cancer. Invasive disease is accompanied by extensive collagen remodeling and crosslinking that contributes to tissue fibrosis and stiffness. Fibrotic breast tumors are associated with an immune desert or immune excluded tumor microenvironment (TME) that functions to promote tumor progression. In particular, tumor-associated macrophages (TAMs) promote tumor invasion and metastasis and, drive immune suppression allowing tumors to evade intrinsic anti-tumor immune responses. Here, we show that collagen remodeling and crosslinking and tissue stiffness associate with DCIS progression and recurrence to invasion in patient tissues. The fibrotic and stiff TME promotes DCIS progression in a mouse model in part by inducing a suppressive TAM phenotype characterized by epigenetic and metabolic reprogramming that accompanies an impaired pro-inflammatory gene signature, as seen in tolerant macrophages. TAMs can be polarized by toll-like receptor (TLR) agonists to eliminate tumor cells by producing pro-inflammatory cytokines or by stimulating cytotoxic T cells, though these are poor cancer therapies alone. Thus, we hypothesized to improve the TLR agonists anti-tumor effects, we can reprogram the metabolic pathways associated with macrophage tolerance, and these together may control DCIS progression in fibrotic and stiff TMEs. We show that fibrotic TAMs can be reprogrammed with monophosphoryl lipid A (MPLA) and coenzyme A (CoA) to kill tumor cells. MPLA + CoA injected into the mammary fat pad reduces high risk features of DCIS in this breast cancer mouse model. We show that CoA supplementation alters macrophage metabolism by supporting acetyl-CoA production needed for histone acetylation and pro-inflammatory gene transcription. MPLA + CoA reprograms CD206+ TAMs to inducible NO synthase (iNOS)+ macrophages and activates cytotoxic T cells through macrophage-secreted cytokines. This treatment approach for engaging an anti-tumor immune response represents an alternative treatment to that of current invasive surgery options for women with high-risk DCIS. Citation Format: Mary-Kate Hayward, Greg A. Timblin, Jason J. Northey, Connor Stashko, Alastair J. Ironside, E. Shelley Hwang, Valerie M. Weaver. Reprogramming of fibrotic macrophages to control DCIS progression [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B003.

We demonstrate for the first time an entirely molecular beam epitaxy (MBE) approach to high-quality GaAs planar coalescence over embedded dielectric microstructures. Specifically, an all-MBE approach was achieved by developing a new two-stage growth process, merging the MBE growth regimes of III-flux modulated lateral epitaxial overgrowth (LEO) with self-ordered planarization of nonplanar substrates to produce highly selective planar coalescence specifically for embedding [010]-aligned silica gratings patterned on (001) substrates. The resulting planar coalescence returned a smooth (001) surface with surface roughness as low as 3 nm root-mean-square and photoluminescence (PL) equivalent to grating-free controls. In demonstrating high-quality GaAs coalescence, we also report for the first time an intentionally enhanced single InGaAs/GaAs/AlAs quantum well PL test structure seamlessly grown directly above embedded silica gratings, leading to a 1.4× enhancement in PL as a result of both Purcell and extractio...

Invasive lobular carcinoma accounts for 5%–15% of all invasive breast cancers, with a marked increase in incidence rates over the past two decades. Distinctive biological hallmarks of invasive lobular carcinoma include the loss of cell adhesion molecule E-cadherin leading to cells with a discohesive morphology, proliferating into single-file strands and estrogen receptor positivity. These key molecular features can make diagnosis difficult, as invasive lobular carcinoma is challenging to detect both physically and with current standard imaging. Treatment of invasive lobular carcinoma strongly favors endocrine therapy due to low chemosensitivity and lower rates of pathological response as a result. This review will summarize the distinct biological and molecular features of invasive lobular carcinoma, focusing on the diagnostic challenges faced and the subsequent surgical and medical management strategies. Prospective therapeutic options will also be explored, highlighting how furthering our understanding of the unique biology of lobular breast carcinoma is essential in guiding and informing the treatment of patients in the future.

We demonstrate that plasmonic response can be tuned spectrally via the alloy composition of an epitaxial semimetallic film. Specifically, attenuated total reflectance studies show that the surface plasmon resonance of rare-earth monopnictide LaxLu1–xAs alloy films can be tuned across the mid-IR, while lattice-matching to technologically important substrates. The electrical properties are a strong function of the composition, which, in turn, manifests as tunability of the optical properties. The ability to produce tunable (semi)metals that can be epitaxially integrated with III–V emitters and absorbers is expected to enable a new generation of novel nanophotonic device architectures and functionality.

Integration of embedded dielectric structures with crystalline III-V materials has generated significant interest, due to a host of important applications and material improvements that are central to high performance optoelectronic devices. The core challenge is the production of high-quality crystalline layers grown above embedded dielectric materials, requiring the growth processes of both lateral epitaxial overgrowth (LEO) and coalescence. In this review article, we provide a detailed and up-to-date description of the recent advances in both LEO and coalescence in III-V materials, from its extension to molecular beam epitaxial growth and high-quality coalescence in InP and GaAs to emerging applications that utilize encapsulated air voids to enhance optical devices. We also explore the epitaxial integration of other materials, particularly metals, with III-V semiconductors.

Self-assembled nanocomposites have been extensively investigated due to the novel properties that can emerge when multiple material phases are combined. Growth of epitaxial nanocomposites using lattice-mismatched constituents also enables strain-engineering, which can be used to further enhance material properties. Here, we report self-assembled growth of highly tensile-strained Ge/In[subscript 0.52]Al[subscript 0.48]As (InAlAs) nanocomposites by using spontaneous phase separation. Transmission electron microscopy shows a high density of single-crystalline germanium nanostructures coherently embedded in InAlAs without extended defects, and Raman spectroscopy reveals a 3.8% biaxial tensile strain in the germanium nanostructures. We also show that the strain in the germanium nanostructures can be tuned to 5.3% by altering the lattice constant of the matrix material, illustrating the versatility of epitaxial nanocomposites for strain engineering. Photoluminescence and electroluminescence results are then discussed to illustrate the potential for realizing devices based on this nanocomposite material., National Science Foundation (U.S.) (DMR 1506371)

Photomixers at THz frequencies offer an attractive solution to fill the THz gap; however, conventional photomixer designs result in low output powers, on the order of microwatts, before thermal failure. We propose an alternative photomixer design capable of orders of magnitude enhancement of continuous-wave THz generation using a metamaterial approach. By forming a metal-semiconductor-metal (MSM) cavity through layering an ultrafast semiconductor material between subwavelength metal-dielectric gratings, tailored resonance can achieve ultrathin absorbing regions and efficient heat sinking. When mounted to a tunable E-patch antenna, gratings also act as vertically biased electrodes, further enhancing photoconductive gain by reducing the carrier path length to nanoscales. Thus, through these multiplicative enhancements, the metamaterial-enhanced photomixer is projected to generate THz powers in the milliwatt range and exceed the Manley-Rowe limit for frequencies less than 2 THz.

Pathological assessment of biopsied or resected central nervous system (CNS) tumours is essential for diagnosis and patient management; both the histological subtype of the tumour and the tumour grade (determined by the World Health Organization (WHO) classification) have major implications for therapy and prognosis. Intraoperative diagnosis of CNS tumours is often required, not only to confirm a clinical diagnosis, but also to determine patient management during the neurosurgical procedure. Recent research has identified a number of genetic abnormalities in primary CNS tumours that have a significant influence on patient management, some of which are now standard investigations that provide information to help determine treatment. This article describes the approach to the intraoperative and histological diagnosis of CNS tumours in adults and children, and reviews recent advances in the genetic analysis of CNS tumours and their clinical significance.

We present a review of 111 patients who were treated over an initial 3-year period with erlotinib. The median treatment time was 68 days and 59% of patients had stopped treatment within the first 3 months. However, 20 patients were on erlotinib for more than 12 months. Performance status and smoking history were the significant prognostic factors. The overall 3-year survival in patients who had never smoked was 26%.

We report the effect of growth interruptions on the structural and optical properties of InAs/InAlGaAs/InP quantum dots using molecular beam epitaxy. We find that the surface quantum dots experience an unintended ripening process during the sample cooling stage, which reshapes the uncapped InAs nanostructures. To prevent this, we performed a partial capping experiment to effectively inhibit structural reconfiguration of surface InAs nanostructures during the cooling stage, revealing that InAs nanostructures first form quantum dashes and then transform into quantum dots via a ripening process. Our result suggests that the appearance of buried InAs/InAlGaAs nanostructures can be easily misunderstood by surface analysis.We report the effect of growth interruptions on the structural and optical properties of InAs/InAlGaAs/InP quantum dots using molecular beam epitaxy. We find that the surface quantum dots experience an unintended ripening process during the sample cooling stage, which reshapes the uncapped InAs nanostructures. To prevent this, we performed a partial capping experiment to effectively inhibit structural reconfiguration of surface InAs nanostructures during the cooling stage, revealing that InAs nanostructures first form quantum dashes and then transform into quantum dots via a ripening process. Our result suggests that the appearance of buried InAs/InAlGaAs nanostructures can be easily misunderstood by surface analysis.

In common with many other countries around the world, the most frequently reported cause of gastrointestinal illness in New Zealand is campylobacteriosis. The poultry industry and regulatory agencies are working to address this. Similarly, the control of Salmonella on poultry has been a focus of industry and regulatory agencies for some time. However, recent data are limited on the prevalence of Campylobacter and Salmonella on retail chicken products in New Zealand. A survey was carried out to determine the prevalence and number of Campylobacter and the prevalence of Salmonella on chickens sold at retail in New Zealand. In total, 163 samples (representing the major chicken processors in New Zealand) were purchased from retail outlets in Auckland, Wellington, and Christchurch and analyzed. Salmonella was not detected on any carcasses or associated external packaging. Campylobacter was isolated from 73 (44.8%) carcass rinse samples collected and from weep water samples associated with 20 (12.3%) of the 163 carcasses, but was not detected on the external packaging of any samples. Counts of Campylobacter present on whole bird carcasses ranged from less than 400 CFU per carcass (not detected) to more than 600,000 CFU per carcass. The overall mean count of Campylobacter on positive carcasses was 3.6 log CFU per carcass. The difference between processing plants in the overall mean count of Campylobacter on broiler carcasses or on the frequency of Campylobacter-positive carcasses was not significant. The levels of Campylobacter found to be associated with broiler carcasses were similar to levels reported in other developed countries.

IntroductionLung cancer survival in Scotland has historically been poor but many changes to the lung cancer services have been introduced and this study was conducted to investigate the impact of these changes on treatment and survival.MethodsData obtained from the Scottish Cancer Registry, South-East Scotland Cancer Network audit and Edinburgh Cancer Centre database were used to conduct a comparison of the management and outcomes of lung cancer patients from South-East Scotland diagnosed in 1995 and in 2002.ResultsData on 971 patients diagnosed in 2002 and 927 in 1995 were analyzed and demonstrated that though the use of treatment overall had not changed (62% in 2002 versus 63% in 1995) the use of potentially curative radiotherapy (15 versus 5% χ2 p < 0.001) and chemotherapy for non-small cell lung cancer (18 versus 7% χ2 p < 0.001) had increased, but not resection rates (11 versus 10%). The use of palliative radiotherapy declined (38% versus 31% χ2 p < 0.001). Patients diagnosed in 2002 had an adjusted hazard of death of 0.7 (95% confidence interval, 0.6–0.8) compared with 1995, with median survival from date of diagnosis of 5.2 versus 4.1 month and 2 year overall survival 15 versus 11% (log rank p = 0.004). Localized disease and younger age were also associated with a reduced hazard of death.ConclusionsPatients diagnosed with lung cancer in Scotland in 2002 had a reduced hazard of death and improved survival compared with 1995. It is hypothesized that this was due in part to improvements in service organization and increased use of treatments likely to increase survival.

ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.

Objective: Report the incidence and type of postoperative complications following neck dissection in patients with advanced stage squamous cell cancer of the laryngopharynx treated with chemoradiotherapy (CRT) and to identify factors predictive of these complications.Method: Design: Retrospective review of case series. Setting: Single institution. Patients: Thirty-three patients with advanced laryngopharyngeal cancer who underwent postchemoradiation neck dissection between 2003 and 2007 were identified. Intervention: Neck dissection, with or without resection of the primary site, in patients following chemoradiotherapy. Main outcome measure: postoperative complications.Results: Thirty-eight neck dissections were carried out in 33 patients (median ± SD age, 59 ± 7.8 years; 85% male). Local wound complications were recorded in 6 (18%) of 33 patients with one mortality from carotid rupture. Complications were seen in 1 (17%) of 6 patients with N1 disease, 5 (23%) of 22 patients with N2, and 0 of 5 patients w...

Objective: 1) Determine the rate of residual neck node disease in patients with squamous cell carcinoma of the larynx, hypopharynx, and oropharynx undergoing neck dissection post-chemoradiation; and 2) Determine the impact on outcome.Method: Design: Retrospective case series. Patients: Thirty-three consecutive patients with residual neck disease following chemoradiotherapy for advanced stage laryngopharyngeal cancer were identified at a single institution between May 2003 and October 2007. Main outcome measure: Neck node pathological positivity, neck recurrence free survival, and disease specific survival.Results: Thirty-eight neck dissections were carried out in 33 patients (median ± STD age, 59 ± 7.8 years; 85% male). The oropharynx was the most common primary site (n = 27; 73%). The follow-up duration ranged from 9 to 61 months. Pathologically, 39.4% (13/33) of patients had viable tumor cells identified in dissection specimen. Three patients (9%) developed primary site recurrence. One patient (3%) died...

Recent research efforts are directed towards the exploration of the energy of the turbulent atmosphere to significantly enhance the performance of aircraft. Of particular interest is “energy harvesting” in order to reduce the drag of small and medium sized uninhabited airborne vehicles (UAV). Most of these energy-harvesting approaches rely on active control systems that detect and exploit the energy of atmospheric disturbances. A different, passive approach to make use of the energy of atmospheric gusts can be accomplished with a wing whose elastic behavior, that is its bending and torsion characteristics, are tailored in an appropriate manner. Relying solely on the dynamic response of the aircraft and its structure, the aircraft-energy state can be elevated even when passing through a gust with an overall zero-net air-mass motion. The required aeroelastic tailoring is relatively easily accomplished with composite materials. The advantage of this approach is that the drag reduction is achieved passively without the need of a complex flight-control and sensor system. A simple analysis is being introduced that shows the response of different aircraft configurations to various gust profiles. Drag reductions of nearly 30-percent appear possible for wings that can rigidly twist and whose shear center is ahead of the aerodynamic center.

Purpose To report the results from continuous, hyperfractionated, accelerated radiotherapy (CHART) used as the standard fractionation for radical RT in the management of non–small cell lung cancer (NSCLC) in five United Kingdom centers. Methods and Materials In 2005, the CHART consortium identified six U.K. centers that had continued to use CHART after the publication of the CHART study in 1997. All centers had been using CHART for >5 years and agreed to use a common database to audit their results. Patients treated with CHART between 1998 and December 2003 were identified to allow a minimum of 2 years of follow-up. Patient demographics, tumor characteristics, treatment details, and survival were recorded retrospectively. Five centers completed the data collection. Results A total of 583 patients who had received CHART were identified. Of these patients, 69% were male, with a median age of 68 years (range, 31–89); 83% had performance status 0 or 1; and 43% had Stage I or II disease. Of the 583 patients, 99% received the prescribed dose. In only 4 patients was any Grade 4-5 toxicity documented. The median survival from the start of RT was 16.2 months, and the 2-year survival rate of 34% was comparable to that reported in the original study. Conclusion The results of this unselected series have confirmed that CHART is deliverable in routine clinical practice, with low levels of toxicity. Importantly, this series has demonstrated that the results of CHART reported from the randomized trial can be reproduced in routine clinical practice.

To determine whether the introduction of early concomitant chemoradiotherapy for patients with limited stage small cell lung cancer (LS-SCLC) has resulted in acceptable outcomes and toxicity in a UK practice.The case records of all patients with LS-SCLC treated with chemoradiotherapy from July 2001 to 2004 were reviewed, and subjected to descriptive statistics and proportional hazards analysis.Concomitant chemoradiotherapy was delivered to 30 patients and sequential chemoradiotherapy was delivered to 36 patients. The former patients tended to be younger (mean 58.9 vs 64.1 years, P=0.01); the latter patients tended to have bulkier disease. There was no difference in performance status, but cisplatin was given more often in the former group (90% vs 44%, P0.0001). Grade 3 acute oesophagitis occurred in less than 10% of either group and there were no cases of grade 3 or greater pneumonitis. Two-year actuarial survival for the concomitant group was 53% (95% confidence interval 36-71%) and 36% (95% confidence interval 20-52%) for the sequential group (P=0.018). Proportional hazards analysis showed an increased hazard of death with increasing performance status and age, sequential therapy and the use of cisplatin with sequential therapy.Concomitant chemoradiotherapy can be safely given in a UK population with outcomes comparable with those reported in North American series.

This experimental investigation aims at revealing the mechanical behaviour and failure pattern of direct fibre-reinforced resin-bonded dental bridge with various designs. To evaluate the overall effects of some newly developed dental materials, in the experiment, genuine composite dental bridge specimens are prepared and tested. The ultimate load, stiffness and mode at the failure of the bridges are measured and compared with the design variations. A good agreement between test and some clinical observations is demonstrated. It is verified that the weakest region appears across the pontic-abutment interface in the composite bridges. This study suggests that the composite bridges reinforced by fibres and supported by adjacent teeth could be of a higher structural strength and stiffness; therefore would provide better clinical performances.

Capecitabine is preferentially converted to 5-fluorouracil within tumours, exploiting the higher levels of thymidine phosphorylase (TP) found in areas of poor perfusion and hypoxia. In addition radiation leads to up regulation of TP expression. To exploit these advantages of capecitabine as a synchronous chemoradiotherapy agent patients with advanced squamous cell carcinoma of the head and neck were recruited into a phase I non-randomised dose finding study. Capecitabine was given twice daily, 7 days a week at a dose starting at 350 mg/m(2) bid. Radiotherapy using a beam directed technique was prescribed to 55 Gy in 20 fractions over 4 weeks. A total of 24 patients were treated. Dose-limiting toxicity (grade IV mucositis) was reached at a capecitabine dose of 550 mg/m(2) bid. Radiotherapy was completed without delay in all cases. There was no systemic drug related toxicity. Capecitabine offers the prospect of an orally administered drug for use synchronously with radiotherapy, which in doses up to 500 mg/m(2) bid is well tolerated.

Background CHHS policy calls for staff to complete advance care plans (including a statement of choices) for patients with chronic disease. Numbers of completed plans are low, partly because some patients do not wish to complete one, and partly due to practical barriers to completion. Aim To overcome practical barriers to completion of advance care plans. Methods From April 2011 our Care Coordination Service established a fortnightly home- based Advance Care Planning Clinic, in which two staff visit patients at their home. In August 2012 this was supplemented by a fortnightly hospital-based clinic. Patients can be booked into either clinic. In the clinic, an Advance Care Plan is prepared comprising of a Statement of Choices and may include Enduring Power of Attorney, witnessed by an authorised clinic staff member. Partners are also offered the opportunity to complete their advance care plan at this time. Results In January–March 2011, prior to the commencement of the clinic, there were 54 patients receiving care coordination of whom 19 (35%) had a completed advance care plan, including a Statement of Choices. In October–December 2012 there were 89 patients who had received care coordination of whom 35 (39%) had a completed advance care plan. Conclusion The establishment of Advance Care Planning Clinics has been a practical way to help overcome multifactorial barriers to preparing a Statement of Choices, providing increased access opportunities and support for timely completion. This approach enabled staff to improve completion rates whilst managing a 65% caseload increase.

We show that the optical properties of a metal-nonlinear dielectric grating can be precisely described by a uniform nonlinear dielectric slab. Based upon such a metamaterial mapping, we show that the effective optical nonlinearity in a metal-dielectric grating can be enhanced by orders of magnitude higher than that of the underlying nonlinear dielectric material, is broadband, and can be operated at a low quality-factor regime so as to have an extremely short intrinsic temporal response of a few picoseconds. Furthermore, we demonstrate extraordinary harmonic generation efficiency enhancement and large threshold-power reduction in bistability.

We demonstrate the growth of high‐quality, single crystal, rocksalt LaAs on III‐V substrates; employing thin well-behaved LuAs barriers layers at the III-V/LaAs interfaces to suppress nucleation of other LaAs phases, interfacial reactions between GaAs and LaAs, and polycrystalline LaAs growth. This method enables growth of single crystal epitaxial rocksalt LaAs with enhanced structural and electrical properties. Temperature-dependent resistivity and optical reflectivity measurements suggest that epitaxial LaAs is semimetallic, consistent with bandstructure calculations in literature. LaAs exhibits distinct electrical and optical properties, as compared with previously reported rare-earth arsenide materials, with a room-temperature resistivity of ∼459 μΩ-cm and an optical transmission window >50% between ∼3-5 μm.

The protein misfolding cyclic amplification (PMCA) technique allows for the in vitro production of protease-resistant prion protein (PrPres) using a seed of disease-associated prion protein (PrPsc) to convert normal cellular prion protein (PrPc). This system has been developed using brain tissue from scrapie infected hamsters to provide the seed and normal uninfected hamster brain to provide PrPc substrate and the required conversion factors. These are mixed and subjected to repeated rounds of sonication and incubation. Extremely low concentrations of PrPsc, such as those present in blood, have been detectable. In order to adapt this method for use in CJD research and in the development of diagnostic tests for human prion diseases it will be necessary to identify a source of human PrPc and co-factors that support amplification of human PrPsc. We have tested whether human autopsy tissues held at the National CJD Surveillance Unit support PMCA. Using a seed extract from variant CJD brain mixed with homogenates of nonCJD neurological control brain we have been able to effect a >600-fold increase in the detection limit of PrPres, as determined by Western Blotting. Further development of this technique in concert with high sensitivity PrPsc detection methods, such as conformation dependent immunoassay, may result in a method capable of acting as a confirmatory assay for disease-associated prion protein in human tissues and biological fluids such as blood.

Community-based models for counseling adults about new careers, education, and life goals present exciting new opportunities for adult learning and dcuelopmmt.

SUMMARYAn outbreak of infection due toStreptococcus zooepidemicus(Lancefield Group C) is described. At least 11 patients were affected and the infection was responsible for, or contributed to, the deaths of seven of these. Clinical features included septicaemia, meningitis and endocarditis. The source of infection was unpasteurized milk from a dairy herd with mild intermittent mastitis.

One of the more pervasive and important innovations of adult education practice in the seventies can be seen in full blossom in the educational guidance and information centre, a service which specializes in counselling adults about learning opportunities. While most visible in the United States with some 300 centres, similar organizations now exist in many other countries; one European centre in fact predates the seventies and may have pioneered the concept. In 1978 and 1979, the author visited various communities in North America and Europe in search of models for counselling adults about new careers, education options and life goals. This paper describes four centres and discusses how they exemplify aspects of a variety of models for organizing counselling services.