18F-FDG-PET in guided dose-painting with intensity modulated radiotherapy in oropharyngeal tumours: A phase I study (FiGaRO).

BACKGROUND AND PURPOSE: The FiGaRO trial assessed the feasibility and safety of using an FDG-PET-based dose-painting technique to deliver a radiotherapy (RT) boostto the FDG-avid primary tumour in patients with locally advanced high and intermediate risk oropharyngeal cancer. MATERIALS AND METHOD: Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5 Gy in30 fractions delivered using a simultaneous integrated boost Intensity Modulated RT (SIB-IMRT) technique. RT was delivered with concomitant Cisplatin following 2 cycles of induction chemotherapy. The primary outcome was the incidence of grade ≥ 3 late mucosal toxicity 12 months post-treatment, with an excess rate of >10% regarded as unacceptable. RESULTS: Twenty-nine patients were included and twenty-four were treated between 2014 and 2018, in two UK centres. Median follow-up was 36 months (range 4-56 months). Pre-defined planning target volume objectives and organ at risk dose constraints were met in all cases. There were no incidents of acute grade 4 toxicity. There were 4 cases of grade ≥ 3 mucosal toxicity at 12 months post-treatment (19.1%). There were no cases of persistent mucosal ulceration at 12 months. Overall survival at 3-years was 87.5%, 92.9% for intermediate and 70.0% for high risk patients. CONCLUSION: Late toxicity rates, although higher than anticipated, are comparable to contemporary published data for standard dose chemo-IMRT. Results suggest improved 3y survival rates for high risk patients. This approach merits further investigation. ClinicalTrials.gov Identifier: NCT02953197.

Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial.

PURPOSE: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. METHODS: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. RESULTS: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. CONCLUSION: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. TRIAL REGISTRATION: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063.

Correction to: Practical issues and limitations of brain attenuation correction on a simultaneous PET-MR scanner.

An amendment to this paper has been published and can be accessed via the original article.

Practical issues and limitations of brain attenuation correction on a simultaneous PET-MR scanner.

BACKGROUND: Despite the advent of clinical PET-MR imaging for routine use in 2011 and the development of several methods to address the problem of attenuation correction, some challenges remain. We have identified and investigated several issues that might affect the reliability and accuracy of current attenuation correction methods when these are implemented for clinical and research studies of the brain. These are (1) the accuracy of converting CT Hounsfield units, obtained from an independently acquired CT scan, to 511 keV linear attenuation coefficients; (2) the effect of padding used in the MR head coil; (3) the presence of close-packed hair; (4) the effect of headphones. For each of these, we have examined the effect on reconstructed PET images and evaluated practical mitigating measures. RESULTS: Our major findings were (1) for both Siemens and GE PET-MR systems, CT data from either a Siemens or a GE PET-CT scanner may be used, provided the conversion to 511 keV µ-map is performed by the PET-MR vendor's own method, as implemented on their PET-CT scanner; (2) the effect of the head coil pads is minimal; (3) the effect of dense hair in the field of view is marked (> 10% error in reconstructed PET images); and (4) using headphones and not including them in the attenuation map causes significant errors in reconstructed PET images, but the risk of scanning without them may be acceptable following sound level measurements. CONCLUSIONS: It is important that the limitations of attenuation correction in PET-MR are considered when designing research and clinical PET-MR protocols in order to enable accurate quantification of brain PET scans. Whilst the effect of pads is not significant, dense hair, the use of headphones and the use of an independently acquired CT-scan can all lead to non-negligible effects on PET quantification. Although seemingly trivial, these effects add complications to setting up protocols for clinical and research PET-MR studies that do not occur with PET-CT. In the absence of more sophisticated PET-MR brain attenuation correction, the effect of all of the issues above can be minimised if the pragmatic approaches presented in this work are followed.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

Specific recommendations for accurate and direct use of PET-CT in PET guided radiotherapy for head and neck sites.

PURPOSE: To provide specific experience-based guidance and recommendations for centers wishing to develop, validate, and implement an accurate and efficient process for directly using positron emission tomography-computed tomography (PET-CT) for the radiotherapy planning of head and neck cancer patients. METHODS: A PET-CT system was modified with hard-top couch, external lasers and radiotherapy immobilization and indexing devices and was subject to a commissioning and quality assurance program. PET-CT imaging protocols were developed specifically for radiotherapy planning and the image quality and pathway tested using phantoms and five patients recruited into an in-house study. Security and accuracy of data transfer was tested throughout the whole data pathway. The patient pathway was fully established and tested ready for implementation in a PET-guided dose-escalation trial for head and neck cancer patients. RESULTS: Couch deflection was greater than for departmental CT simulator machines. An area of high attenuation in the couch generated image artifacts and adjustments were made accordingly. Using newly developed protocols CT image quality was suitable to maintain delineation and treatment accuracy. Upon transfer of data to the treatment planning system a half pixel offset between PET and CT was observed and corrected. By taking this into account, PET to CT alignment accuracy was maintained below 1 mm in all systems in the data pathway. Transfer of structures delineated in the PET fusion software to the radiotherapy treatment planning system was validated. CONCLUSIONS: A method to perform direct PET-guided radiotherapy planning was successfully validated and specific recommendations were developed to assist other centers. Of major concern is ensuring that the quality of PET and CT data is appropriate for radiotherapy treatment planning and on-treatment verification. Couch movements can be compromised, bore-size can be a limitation for certain immobilization techniques, laser positioning may affect setup accuracy and couch deflection may be greater than scanners dedicated to radiotherapy. The full set of departmental commissioning and routine quality assurance tests applied to radiotherapy CT simulators must be carried out on the PET-CT scanner. CT image quality must be optimized for radiotherapy planning whilst understanding that the appearance will differ between scanners and may affect delineation. PET-CT quality assurance schedules will need to be added to and modified to incorporate radiotherapy quality assurance. Methods of working for radiotherapy and PET staff will change to take into account considerations of both parties. PET to CT alignment must be subject to quality control on a loaded and unloaded couch preferably using a suitable emission phantom, and tested throughout the whole data pathway. Data integrity must be tested throughout the whole pathway and a system included to verify that delineated structures are transferred correctly. Excellent multidisciplinary team communication and working is vital, and key staff members on both sides should be specifically dedicated to the project. Patient pathway should be clearly devised to optimize patient care and the resources of all departments. Recruitment of a cohort of patients into a methodology study is valuable to test the quality assurance methods and pathway.

Recommendations for the use of PET and PET-CT for radiotherapy planning in research projects.

With the increasing use of positron emission tomography (PET) for disease staging, follow-up and therapy monitoring in a number of oncological indications there is growing interest in the use of PET and PET-CT for radiation treatment planning. In order to create a strong clinical evidence base for this, it is important to ensure that research data are clinically relevant and of a high quality. Therefore the National Cancer Research Institute PET Research Network make these recommendations to assist investigators in the development of radiotherapy clinical trials involving the use of PET and PET-CT. These recommendations provide an overview of the current literature in this rapidly evolving field, including standards for PET in clinical trials, disease staging, volume delineation, intensity modulated radiotherapy and PET-augmented planning techniques, and are targeted at a general audience. We conclude with specific recommendations for the use of PET in radiotherapy planning in research projects.

The unfolded protein response controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress.

The family of ADAM (a disintegrin and metalloproteinase) proteins has been implicated in tumor initiation and progression. ADAM17/tumor necrosis factor-α (TNFα)-converting enzyme (TACE) has been initially recognized to release TNFα as well as its receptors (TNFRs) from the membrane. ADAM17, TNFα and TNFR have been found upregulated in cancer patients, although the underlying mechanisms remain largely unknown. As hypoxia is a hallmark of cancer that can lead to severe stress conditions accumulating in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), we investigated the role of these stress conditions in the regulation of ADAM17 and release of TNFR1.We found that severe hypoxia induced ADAM17 expression and activity. Although hypoxia-inducible factor 1α (HIF1α) was important to maintain basal ADAM17 mRNA levels during moderate hypoxia, it was not sufficient to induce ADAM17 levels under severe hypoxia. Instead, we found that ADAM17 induction by severe hypoxia can be mimicked by ER stressors such as Thapsigargin and occurs as a consequence of the activation of the PERK/eIF2α/ATF4 and activating transcription factor 6 (ATF6) arms of UPR in several tumor cell lines. ADAM17 expression was also increased in xenografts displaying ER stress because of treatment with the vascular endothelial growth factor (VEGF) inhibitory antibody Bevacizumab. Additionally, severe hypoxia and ER stress activated ADAM17 and ectodomain shedding of TNFR1 involving mitogen-activated protein (MAP) kinases and reactive oxygen species (ROS). Collectively, these results show that ADAM17 is a novel UPR-regulated gene in response to severe hypoxia and ER stress, which is actively involved in the release of TNFR1 under these conditions. These data provide a novel link between severe hypoxic stress conditions and inflammation in the tumor environment.

Imaging gene delivery in a mouse model of congenital neuronal ceroid lipofuscinosis.

Adeno-associated virus (AAV)-mediated gene replacement for lysosomal disorders have been spurred by the ability of some serotypes to efficiently transduce neurons in the brain and by the ability of lysosomal enzymes to cross-correct among cells. Here, we explored enzyme replacement therapy in a knock-out mouse model of congenital neuronal ceroid lipofuscinosis (NCL), the most severe of the NCLs in humans. The missing protease in this disorder, cathepsin D (CathD) has high levels in the central nervous system. This enzyme has the potential advantage for assessing experimental therapy in that it can be imaged using a near-infrared fluorescence (NIRF) probe activated by CathD. Injections of an AAV2/rh8 vector-encoding mouse CathD (mCathD) into both cerebral ventricles and peritoneum of newborn knock-out mice resulted in a significant increase in lifespan. Successful delivery of active CathD by the AAV2/rh8-mCathD vector was verified by NIRF imaging of mouse embryonic fibroblasts from knock-out mice in culture, as well as by ex vivo NIRF imaging of the brain and liver after gene transfer. These studies support the potential effectiveness and imaging evaluation of enzyme replacement therapy to the brain and other organs in CathD null mice via AAV-mediated gene delivery in neonatal animals.

Regulation of autophagy by ATF4 in response to severe hypoxia.

Activating transcription factor 4 (ATF4) is a transcription factor induced under severe hypoxia and a component of the PERK pathway involved in the unfolded protein response (UPR), a process that protects cells from the negative consequences of endoplasmic reticulum (ER) stress. In this study, we have used small interfering RNA (siRNA) and microarray analysis to provide the first whole-genome analysis of genes regulated by ATF4 in cancer cells in response to severe and prolonged hypoxic stress. We show that ATF4 is required for ER stress and hypoxia-induced expansion of autophagy. MAP1LC3B (LC3B) is a key component of the autophagosomal membrane, and in this study we demonstrate that ATF4 facilitates autophagy through direct binding to a cyclic AMP response element binding site in the LC3B promoter, resulting in LC3B upregulation. Previously, we have shown that Bortezomib-induced ATF4 stabilization, which then upregulated LC3B expression and had a critical role in activating autophagy, protecting cells from Bortezomib-induced cell death. We also showed that severe hypoxia stabilizes ATF4. In this study, we demonstrate that severe hypoxia leads to ER stress and induces ATF4-dependent autophagy through LC3 as a survival mechanism. In summary, we show that ATF4 has a key role in the regulation of autophagy in response to ER stress and provide a direct mechanistic link between the UPR and the autophagic machinery.

The acoustic properties, centered on 20 MHZ, of an IEC agar-based tissue-mimicking material and its temperature, frequency and age dependence.

The purpose of this study was to characterize the ultrasonic properties of agar-based tissue-mimicking materials (TMMs) at ultrasound frequencies centered around 20 MHz. The TMM acoustic properties measured are the amplitude attenuation coefficient alpha (dB cm(-1)MHz(-1)), the speed of sound (ms(-1)) and the backscattered power spectral density (distribution of power per unit frequency normalized to the total received power) characteristics of spectral slope (dB MHz(-1)), y-axis intercept (dB) and reflected power (dB). The acoustic properties are measured over a temperature range of 22 to 37 degrees C. An intercomparison of results between two independent ultrasound measurement laboratories is also presented. A longitudinal study of the acoustic properties over a period of two years is also detailed, and the effect of water immersion on the acoustic properties of TMM is measured. In addition, the physical parameters of mass density rho (kg m(-3)) and specific heat capacity C (J kg(-1) K(-1)) are included. The measurement techniques used were based on the substitution technique using both broadband and narrowband pulses centered on 20 MHz. Both the attenuation coefficient and speed of sound (both group and phase) showed good agreement with the expected values of 0.5 dB cm(-1) MHz(-1) and 1540 ms(-1), respectively, with average values over the three-year period of 0.49 dBcm(-1)MHz1 (SD +/- 0.05) and 1540.9 ms(-1) (SD +/- 8.7). These results also showed agreement between the two independent measurement laboratories. Speed of sound and attenuation coefficient were shown to change with temperature with rates of + 2.1 m s(-1) degrees C(-1) and -0.005 dB cm(-1) MHz(-1) degrees C(-1), respectively. Attenuation changed linearly with frequency at the high frequency range of 17 to 23 MHz, and speed of sound was found to be independent of frequency in this range. The spectral slope of relative backscattered power for the material increased with frequency at typically 1.5 dB MHz(-1). This compared favorably with theoretical spectral slope values, calculated for a variety of scatterer sizes, albeit at a lower frequency range. It is also noticed that, on extrapolation back to lower frequencies, the backscatter is comparable with that measured at 7 MHz. Overall, this non-commercial agar-based TMM is shown to perform as expected at the higher frequency range of 17 to 23 MHz and is seen to retain its acoustic properties of attenuation and speed of sound over a three-year period.

Thiopurine methyltransferase and 6-thioguanine nucleotide measurement: early experience of use in clinical practice.

BACKGROUND: Azathioprine and 6-mercaptopurine (6-MP) are well established for the treatment of inflammatory bowel disease (IBD). Assessing thiopurine methyltransferase (TPMT) status has been recommended to reduce the risk of serious toxicity. Measuring red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) concentrations has been recommended for dose adjustment. AIM: To describe the results of measuring TPMT activity and genotype, and 6-TGN concentration in New Zealand. METHODS: Canterbury Health Laboratories provided these analyses for New Zealand. Those with low TPMT activity also underwent genotyping. All results were collated and analysed descriptively. 6-TGN concentrations were correlated with the dose of thiopurine when known. RESULTS: TPMT enzyme activity (range 1-22 U/mL) from 574 patients showed a trimodal distribution. Genotyping results matched this distribution with only mild overlap between (*1/*1) homozygote and (*1/*3) heterozygote groups. One patient without TPMT measurement before therapy had life-threatening neutropenia and was later found to have (*3/*3) genotype. TPMT analysis probably prevented two further such cases. Of 884 6-TGN concentrations (range 0-1434 pmol/10(8) RBC), 41, 39 and 20% were within, below, and above the therapeutic range of 235-450 pmol/10(8) RBC, respectively. Leucopenia was seen in some patients with high 6-TGN. 6-MMP concentrations in 177 patients with low 6-TGN suggested non-compliance in 31, underdosing in 130, and preferential metabolism of 6-MP to 6-methylmercaptopurine in 16. There was poor correlation between azathioprine dose and 6-TGN concentration (r(2) = 0.002), supporting 6-TGN monitoring. CONCLUSIONS: Measurement of TPMT enzyme activity and 6-TGN concentration has been well-integrated into clinical practice. These tests should reduce the risk of toxicity and improve efficacy with thiopurines in patients with IBD.

Gold color in onions (Allium cepa): a natural mutation of the chalcone isomerase gene resulting in a premature stop codon.

Unusual gold-colored onions were selected from a F3 family originating from a cross between US-type yellow and Brazilian yellow onions. HPLC analysis showed that the gold onions contained a significantly reduced amount of quercetin, the most abundant flavonoid in onions. This result indicated that an early step in the flavonoid biosynthesis pathway might be abnormal in these onions. The expression of flavonoid synthesis genes isolated from onions was examined in gold onions and compared to that in onions of other colors by RT-PCR. The results showed that all genes were transcribed in gold onions as in red onions. In order to identify any critical mutations in flavonoid synthesis genes encoding enzymes involved in early steps of the pathway, the genomic sequence of chalcone isomerase (CHI) was obtained. A premature stop codon and a subsequent single base-pair addition causing a frameshift were identified in the coding region of the CHI gene in the gold onions. Co-segregation of the mutant allele of the CHI gene and the gold phenotype was investigated in the original F2 segregating population. Genotyping of three color groups (red, yellow and gold) of F2 onions revealed perfect co-segregation of the mutant CHI allele with the gold phenotype. All tested gold F2 onions were homozygous for the mutant CHI allele. This perfect co-segregation implies that the presence of a premature stop codon in the gold CHI gene results in an inactive CHI. Inactivation of CHI results in a block in the flavonoid biosynthesis pathway and the accumulation of chalcone derivatives, including a yellow pigment which might be responsible for the gold color in onions.

Pink (P), a new locus responsible for a pink trait in onions (Allium cepa) resulting from natural mutations of anthocyanidin synthase.

A new locus conditioning a pink trait in onions was identified. Unusual pink onions were found in haploid populations induced from an F(1) hybrid between yellow and dark red parents and in F(3) populations originating from the same cross. Segregation ratios of red to pink in F(2), backcross, and F(3) populations indicated that this pink trait is determined by a single recessive locus. RT-PCR was carried out to look for any differential expression of anthocyanin synthesis genes between dark red and pink F(3) lines. The transcript level of anthocyanidin synthase (ANS) was significantly reduced in the pink line. To determine whether this reduced transcription is caused by other regulatory factors or by mutations in the ANS gene itself, ANS gene sequences from both dark red and pink F(3) lines were compared to detect any polymorphisms. Polymorphisms were identified, and subsequently utilized as molecular markers for the selection of ANS alleles. Absolute co-segregation of the pink allele and the ANS allele from the pink line was observed in parents, F(1) and F(3) populations. These results indicate that reduced transcription of the ANS gene caused by mutations in a cis -acting element is likely to result in the pink trait in onions.

Effect of multislice scanners on patient dose from routine CT examinations in East Anglia.

As part of the dose optimization process, the Ionising Radiation (Medical Exposure) Regulations 2000 include requirements relating to the assessment of patient dose, and the setting and subsequent review of diagnostic reference levels. In East Anglia, audits of effective dose in CT have been carried out in 1996, 1999 and 2002. In the 2002 audit, nine of the 14 scanners assessed had been replaced since the previous audit. Eight of the new scanners were multislice scanners, acquiring up to 16 slices in a single rotation. The objective of the 2002 audit was to investigate the effect of the introduction of these multislice scanners on patient doses from routine CT examinations. Exposure parameters were collected for 10 different types of routine CT examination. In excess of 550 sets of patient data were obtained. For each of these, effective doses were calculated using the results of Monte Carlo simulations published by the National Radiological Protection Board. Averaged across all 10 examinations, regional mean effective doses are 34% higher than in 1999. The multislice scanners in the region give, on average, 35% more effective dose than the single-slice scanners. The effect of collimation in multislice scanners makes these effective dose differences most notable for examinations that use narrow slice widths. Further optimization of exposures on multislice scanners has the potential to reduce the differences observed between single-slice and multislice doses. However, when taken in combination with the increased use of CT in many hospitals, the effective dose increases observed are likely to result in a significant increase in the already substantial collective radiation dose from CT.

Macro-alkaline phosphatase due to IgG kappa complex: demonstration with polyethylene glycol precipitation and immunofixation.

An otherwise unexplained, persistently elevated plasma alkaline phosphatase concentration in a 71-year-old woman was found to be attributable to the presence of macro-alkaline phosphatase using polyethylene glycol precipitation. Gel filtration showed two high MW peaks with masses of about 330 kDa and 560 kDa. The alkaline phosphatase (ALP) complex was characterized by immunoelectrophoresis as a complex with IgG with kappa light chains.

Dynamic sensitivity of ATP-sensitive K(+) channels to ATP.

ATP and MgADP regulate K(ATP) channel activity and hence potentially couple cellular metabolism to membrane electrical activity in various cell types. Using recombinant K(ATP) channels that lack sensitivity to MgADP, expressed in COSm6 cells, we demonstrate that similar on-cell activity can be observed with widely varying apparent submembrane [ATP] ([ATP](sub)). Metabolic inhibition leads to a biphasic change in the channel activity; activity first increases, presumably in response to a fast decrease in [ATP](sub), and then declines. The secondary decrease in channel activity reflects a marked increase in ATP sensitivity and is correlated with a fall in polyphosphoinositides (PPIs), including phosphatidylinositol 4,5-bisphosphate, probed using equilibrium labeling of cells with [(3)H]myo-inositol. Both ATP sensitivity and PPIs rapidly recover following removal of metabolic inhibition, and in both cases recovery is blocked by wortmannin. These data are consistent with metabolism having a dual effect on K(ATP) channel activity: rapid activation of channels because of relief of ATP inhibition and much slower reduction of channel activity mediated by a fall in PPIs. These two mechanisms constitute a feedback system that will tend to render K(ATP) channel activity transiently responsive to a change in [ATP](sub) over a wide range of steady state concentrations.

Conducting adolescent sexuality research in schools: lessons learned.

PIP: Research that analyzes school-based health education programs usually includes the intervention's strategies, the instrument used to gauge its effectiveness, the sample sizes, and results. Issues related to recruiting and retaining of participants are rarely studied. Using school-based personnel as allies has been suggested in previous studies, but no studies have reported the outcome of this strategy when the research involves the topic of sexuality education. In this paper, the authors describe their experience using such a strategy in a longitudinal evaluation of Reducing the Risk curriculum, using 1141 adolescents within the 12 intervention schools in Maine in order to explore its impact on adolescent attitudes and behavior. The evaluation explored the supports and barriers to adopting curricula, the extent to which teachers implemented them and the types of modifications they made. Overall, the authors concluded that modifying a curriculum during implementation can reduce its effectiveness.^ieng

The internal consistency of the child abuse potential inventory with adolescent mothers.

In this study, 105 adolescents completed the Child Abuse Potential Inventory (CAP) at an average of 2 months postpartum. The purpose was to assess the reliability (internal consistency) of the CAP with adolescent mothers. The second purpose was to begin to establish a line of inquiry that examines the value of using the CAP with this population. The results showed that the alpha reliabilities were low for the CAP abuse scale (0.65) and low to moderate for its six subscales (range 0.59-0.74). The conclusion was drawn that further research is needed to understand the psychometric properties of the CAP with adolescent mothers.