Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study.

BACKGROUND: Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). PATIENTS AND METHODS: CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. RESULTS: The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. CONCLUSIONS: This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM(+)) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.

Patient journey to a specialist amyotrophic lateral sclerosis multidisciplinary clinic: an exploratory study.

BACKGROUND: The multidisciplinary approach in the management of Amyotrophic Lateral Sclerosis (ALS) has been shown to provide superior care to devolved care, with better survival, improved quality of care, and quality of life. Access to expert multidisciplinary management should be a standard for patients with ALS. This analysis explores the patient journey from symptom onset and first engagement with health services, to the initial visit to a specialist ALS Multidisciplinary Clinic (MDC) in Dublin, Ireland. METHODS: A retrospective exploratory multi-method study details the patient journey to the MDC. Data from medical interviews and systematic chart review identifies interactions with the health services and key timelines for thirty five new patients presenting with a diagnosis of ALS during a 6 month period in 2013. RESULTS: The time from first symptom to diagnosis was a mean of 16 months (median 13 months), with a mean interval of 19 months (median 14.6) from first symptoms to arrival at the MDC. The majority of patients were seen by a general practitioner, and subsequently by neurology services. There was an average of four contacts with health services and 4.8 investigations/tests, prior to their first Clinic visit. On the first visit to the MDC patients are linked into an integrated 'system' that can provide specialist care and link with voluntary, palliative and community services as required. CONCLUSIONS: Engagement with a multidisciplinary team has implications for service utilization and quality of life of patients and their families. We have demonstrated that barriers exist that delay referral to specialist services. Comprehensive data recording and collection, using multiple data sources can reconstruct the timelines of the patient journey, which can in turn be used to identify pathways that can expedite early referral to specialist services.

Widespread service fragmentation for patients and families with tuberous sclerosis complex (TSC) in the Republic of Ireland.

Background: Tuberous sclerosis complex (TSC) is a rare approximate 1:6000 birth incidence, a genetic disease with a wide variability of physical and neuropsychiatric symptoms. Patients require lifelong care from multiple healthcare specialities, for which International and United Kingdom (UK) TSC consensus recommendations exist. Personalised care delivered by a centralised coordinated team of TSC experts is recommended. There is no such service for the estimated 600 TSC patients in the Republic of Ireland (ROI) and there is a paucity of information regarding the healthcare of this group. Purpose: Evaluate the baseline care of patients with TSC attending epilepsy services in the Republic of Ireland (ROI) against UK TSC consensus recommendations. Methods: Patients with a diagnosis of TSC attending 12 adult and paediatric epilepsy centres in the ROI were identified. Clinical audits measured the baseline care of a subset of these patients against UK, TSC clinical recommendations. Data was anonymised and analysed at Trinity College Dublin. Results: One hundred thirty-five TSC patients attending twelve epilepsy centres were identified. Adults (n = 67) paediatric (n = 68). The care of 83 patients was audited (n = 63 ≥ 18 years) and (n = 20 < 18 years). Many baseline tests were completed, however, they required intra or interhospital referral. Care appears fragmented and there was no evidence of formal disease surveillance plans. Conclusions: The number of TSC patients attending epilepsy services is lower than expected (n = 135). Specialist services and treatments for TSC are available through informal referral pathways. Although UK, TSC consensus baseline recommendations are roughly adhered to, care is fragmented. Increased coordination of care could benefit disease management. Supplementary Information: The online version contains supplementary material available at 10.1007/s44162-024-00049-8.

Relative accuracy and availability of an Irish National Database of dispensed medication as a source of medication history information: observational study and retrospective record analysis.

WHAT IS KNOWN AND OBJECTIVE: The medication reconciliation process begins by identifying which medicines a patient used before presentation to hospital. This is time-consuming, labour intensive and may involve interruption of clinicians. We sought to identify the availability and accuracy of data held in a national dispensing database, relative to other sources of medication history information. METHODS: For patients admitted to two acute hospitals in Ireland, a Gold Standard Pre-Admission Medication List (GSPAML) was identified and corroborated with the patient or carer. The GSPAML was compared for accuracy and availability to PAMLs from other sources, including the Health Service Executive Primary Care Reimbursement Scheme (HSE-PCRS) dispensing database. RESULTS: Some 1111 medication were assessed for 97 patients, who were median age 74 years (range 18-92 years), median four co-morbidities (range 1-9), used median 10 medications (range 3-25) and half (52%) were male. The HSE-PCRS PAML was the most accurate source compared to lists provided by the general practitioner, community pharmacist or cited in previous hospital documentation: the list agreed for 74% of the medications the patients actually used, representing complete agreement for all medications in 17% of patients. It was equally contemporaneous to other sources, but was less reliable for male than female patients, those using increasing numbers of medications and those using one or more item that was not reimbursable by the HSE. WHAT IS NEW AND CONCLUSION: The HSE-PCRS database is a relatively accurate, available and contemporaneous source of medication history information and could support acute hospital medication reconciliation.

Luminescence Enhancement by the Introduction of Disorder into Poly(p-phenylene vinylene).

A method is described for increasing luminescence in poly(p-phenylene vinylene) (PPV) light-emitting diodes. Cis linkages were engineered into the PPV chain. These linkages interrupt conjugation and interfere with the packing of the polymer chains, which results in the formation of amorphous PPV. Large-area electroluminescent devices were prepared from this polymer. Devices made of an aluminum electrode, PPV as the luminescent layer, and an electron-transporting layer have internal quantum efficiencies of 2 percent, a turn-on voltage of 20 volts, and can carry current densities of 2000 milliamperes per square centimeter. The current density is at least an order of magnitude higher than previously obtained.

Exchanges across land-water-scape boundaries in urban systems: strategies for reducing nitrate pollution.

Conservation in urban areas typically focuses on biodiversity and large green spaces. However, opportunities exist throughout urban areas to enhance ecological functions. An important function of urban landscapes is retaining nitrogen thereby reducing nitrate pollution to streams and coastal waters. Control of nonpoint nitrate pollution in urban areas was originally based on the documented importance of riparian zones in agricultural and forested ecosystems. The watershed and boundary frameworks have been used to guide stream research and a riparian conservation strategy to reduce nitrate pollution in urban streams. But is stream restoration and riparian-zone conservation enough? Data from the Baltimore Ecosystem Study and other urban stream research indicate that urban riparian zones do not necessarily prevent nitrate from entering, nor remove nitrate from, streams. Based on this insight, policy makers in Baltimore extended the conservation strategy throughout larger watersheds, attempting to restore functions that no longer took place in riparian boundaries. Two urban revitalization projects are presented as examples aimed at reducing nitrate pollution to stormwater, streams, and the Chesapeake Bay. An adaptive cycle of ecological urban design synthesizes the insights from the watershed and boundary frameworks, from new data, and from the conservation concerns of agencies and local communities. This urban example of conservation based on ameliorating nitrate water pollution extends the initial watershed-boundary approach along three dimensions: 1) from riparian to urban land-water-scapes; 2) from discrete engineering solutions to ecological design approaches; and 3) from structural solutions to inclusion of individual, household, and institutional behavior.

Acetabular bone defects in THA revision: Reconstruction using morsellised virus-inactivated bone allograft and reinforcement ring. Seven-year outcomes in 95 patients.

BACKGROUND: Acetabular cup loosening is among the main reasons for revision total hip arthroplasty (THA). The implantation of a cryopreserved morsellised bone allograft is a reference method for filling bone defects. However, the outcomes of bone grafts treated with viral inactivation and secured into the host bone (notably using a reinforcement device) are unclear. We therefore retrospectively reviewed cases of acetabular revision with morsellised bone allograft implanted into a reinforcement ring for acetabular revision to assess: (1) clinical survival of the acetabular implant (time to new revision with acetabular component removal), (2) radiological implant survival, (3) and bone graft osseointegration evaluated using Oswestry's criteria. HYPOTHESIS: Virus-inactivated bone allografts provide similar outcomes to cryopreserved allografts. MATERIAL AND METHODS: From 2004 to 2009, 95 patients underwent acetabular revision. There were 60 (63%) females and 35 (37%) males with a mean age of 71.7 years (range: 44.2-90 years). Over 90% of patients had bone defects type 2 or higher in the AAOS classification. Each patient was evaluated after at least 5 years, by an examiner who had not been involved in the revision and who determined the Postel-Merle d'Aubigné (PMA) score and patient satisfaction. We assessed the clinical survival of the acetabular implant (time to new revision with acetabular implant removal), radiological implant survival (migration>5mm, active radiolucent line, failure of graft osseointegration, or reinforcement ring failure), and allograft osteointegration evaluated using Oswestry's criteria. RESULTS: After a mean follow-up of 7years (range: 5.2-10years), 7 (7.4%) patients had been lost to follow-up and 3 (3.4%) had required surgical revision, after 3 to 73 months (for aseptic loosening in 2 cases and infection in 1 case). The estimated 10-year survival rate was 96.2% (95% confidence interval [95%CI]: 88.2-98.7). The mean PMA score at last follow-up had increased significantly, by 2.8 points (p<0.05), to 13.8 (95%CI: 78.4-88.1). Of the 88 re-evaluated patients, 78 (89%) were satisfied or very satisfied. The overall radiological survival rate was 84.5% (95%CI: 78.4-88.1) after a mean of 5.9 years (range: 0.5-10). Allograft osseointegration was satisfactory (Oswestry score≥2) in 95.8% of patients. DISCUSSION: In our population, allografts previously subjected to virus inactivation and implanted into a reinforcement ring produced outcomes similar to those reported previously with cryopreserved allografts. LEVEL OF EVIDENCE: IV, retrospective case-series study.

Chronic care clinics for diabetes in primary care: a system-wide randomized trial.

OBJECTIVE: To evaluate the impact of primary care group visits (chronic care clinics) on the process and outcome of care for diabetic patients. RESEARCH DESIGN AND METHODS: We evaluated the intervention in primary care practices randomized to intervention and control groups in a large-staff model health maintenance organization (HMO). Patients included diabetic patients > or = 30 years of age in each participating primary care practice, selected at random from an automated diabetes registry. Primary care practices were randomized within clinics to either a chronic care clinic (intervention) group or a usual care (control) group. The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor's practice. Chronic care clinics consisted of standardized assessments; visits with the primary care physician, nurse, and clinical pharmacist; and a group education/peer support meeting. We collected self-report questionnaires from patients and data from administrative systems. The questionnaires were mailed, and telephoned interviews were conducted for nonrespondents, at baseline and at 12 and 24 months; we queried the process of care received, the satisfaction with care, and the health status of each patient. Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems. RESULTS: In an intention-to-treat analysis at 24 months, the intervention group had received significantly more recommended preventive procedures and helpful patient education. Of five primary health status indicators examined, two (SF-36 general health and bed disability days) were significantly better in the intervention group. Compared with control patients, intervention patients had slightly more primary care visits, but significantly fewer specialty and emergency room visits. Among intervention participants, we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes, including patient satisfaction and HbA1c levels. CONCLUSIONS: Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes.

Opening-wedge high tibial osteotomy with a secure bone allograft (Osteopure™) and locked plate fixation: Retrospective clinical and radiological evaluation of 69 knees after 7.5years follow-up.

BACKGROUND: Medial opening-wedge high tibial osteotomy (OWHTO) provides reliable and long-lasting benefits, despite the wide range of wedge-filling and internal-fixation techniques used. The purpose of this work was to assess the clinical and radiological outcomes in a case-series of OWHTO performed using a secure bone allograft and locked plate fixation. HYPOTHESIS: The clinical and radiological outcomes of OWHTO with a high-safety bone allograft and locked plate fixation are similar to those reported in previous case-series studies. MATERIALS AND METHODS: A single-centre retrospective design was used to study 69 knees in 64 patients with a mean age of 51.8years (31-53years) and a preoperative hip-knee-ankle (HKA) angle of 173° (165°-180°). The wedge was filled with secure Osteopure™ bone allograft and fixation was achieved using an Integra Surfix(®) locked plate. Mean follow-up was 7.5years (5-9.3years). Clinical and functional outcomes were assessed by determining the IKS and KOOS-PS scores and recording complications related or unrelated to the allograft. The main criterion for assessing OWHTO survival was the time to revision surgery for symptom recurrence. Radiological assessment criteria were the HKA angle, tibial slope, patellar height, and osteoarthritis grade. GESTO criteria were used to evaluate the behaviour of the allograft. RESULTS: Of the 69 knees, 64 (92.8%) were re-evaluated. The survival rate after 9.3years was 95%±2.7% (3 failures managed with arthroplasty). The functional IKS score improved significantly, by 20 points (P<0.001). Mean increases of 7.8° for the HKA angle and 3.5° for tibial slope were recorded. Bone healing without radiological abnormalities was consistently achieved within 6months. There were no complications related to the allograft (infections, allergies; local or systemic toxicity). DISCUSSION: The clinical, radiological, and safety outcomes documented in our study were similar to those reported in earlier work. LEVEL OF EVIDENCE: IV, retrospective case-series study.

Fast and reliable screening of mutations in human tumors: use of multiple fluorescence-based long linker arm nucleotides assay (mf-LLA).

Human tumor samples were screened for point mutations by adapting a mobility-shift assay to automated DNA sizing. This screen identifies the type of point mutation and relative amount of mutated DNA sequences present in a sample. Test samples having known hypoxanthine-guanine phosphoribosyl transferase (hprt)/exon-3 sequence mutations were characterized by: (i) PCR amplification, (ii) fluorescent dye-primer extension with 36-atom linker derived deoxycytosine or deoxyuridine triphosphate and the remaining three natural nucleotides and (iii) sizing of the resulting fluorescently labeled modified strands, using an automated DNA sequencer. Routinely, a range of sizes is observed among the sequence variants of a single DNA target sequence. This is because nucleotide analogs are incorporated into DNA strands in a sequence-dependent manner, resulting in composition-dependent electrophoretic mobility. Thus, point mutations are identified as shifts in mobility between the fluorescently labeled modified strands of the control and test samples. The twenty different hprt/exon-3 single-base substitution mutations tested were easily identified, even at fourfold dilution with control DNA.

Peripheral blood stem cell transplantation in myeloma using CD34 selected cells.

We have performed nine CD34 selection procedures on peripheral blood stem cells harvested from eight patients with myeloma using the Cellpro avidin-biotin immunoaffinity column (Ceprate). They all received CVAMP chemotherapy to maximum response prior to mobilisation. Six of the patients have been transplanted using these cells, one receiving successive autografts. Median absolute cell numbers processed and retrieved were: 31.1 x 10(9) pre-column, 2.07 x 10(8) in the final product and 30.4 x 10(9) in the column waste. Mean CD34 positivity in the product was 49% (range 18.4-98) with a median CD34+ yield of 31.4% (range 21-37.8). IgH PCR was performed and seven of the eight patients were amplifiable. Of these, two were positive in the pre-column product and both of these were successfully purged with a negative result in the final, post-column product. Patients were transplanted with a median of 2.0 x 10(6) CD34+ cells/kg (range 1.5-9.4) following conditioning with melphalan 200 mg/m2. The mean time to recovery of neutrophils to > 0.5 x 10(9)/l and platelets to > 20 x 10(9)/l was 16 and 17 days, respectively. At a mean follow-up of 9 months, four of the six patients transplanted are alive, three of them in complete remission and one in a clinically stable relapse. One has died of disease relapse and one of progressive neurological problems the aetiology of which was uncertain but there was no sign of progression of their myeloma. We conclude that PBSCT using CD34 selected cells is safe and practical in myeloma following remission induction with CVAMP chemotherapy.

The effect of 2450-MHz microwave radiation during microtubular polymerization in vitro.

Exposure to 2450-MHz (cw) microwave radiation causes inhibition of cell division in intact cells and varied in vivo biological effects in both avian and mammalian species. Because these reported effects may result from alterations in the dynamics of microtubule formation, we studied the effects of simultaneous microwave exposure (2450 MHz, cw) during each of the three critical stages of the intracellar polymerization cycle. In addition, using circular dichroism spectroscopy, we studied the effect of microwave irradiation on the secondary structure of purified tubulin polypeptides. These studies were accomplished using specially constructed exposure systems that permit the continuous recording of turbidometric or circular dichroism measurements during simultaneous exposure to microwaves. The baseline turbidity of microtubular protein did not change under the influence of microwave radiation (20 or 200 mW/g SAR) and irradiation had no effect on the light-scattering properties of the depolymerized protein. EGTA-induced polymerization and cold-induced depolymerization patterns were also similar for both control and microwave-irradiated samples. The circular dichroism spectrum of purified tubulin also did not appear to be influenced by microwave irradiation, indicating a lack of effect on the protein secondary structure. The data suggest that the cellular effects of microwaves are not due to changes in microtubular proteins or their rate of polymerization.

Effect of 2450 MHz microwave radiation on hematopoiesis of pregnant mice.

In this study, the influence of 2450 MHz CW microwave radiation on hematopoiesis in pregnant mice was examined. Dams (mice CD-1 strain) were irradiated during Days 1-6 or 6-15 of pregnancy. The animals were irradiated for a total of 8 hr per day (two 4-hr exposures in 9 hr) at an average power density of 30 mW/cm2. Peripheral blood and bone marrow samples were obtained on Day 18 of pregnancy. The total leukocyte and differential leukocyte counts of peripheral blood samples were not affected by either exposure regimen. In addition, no effects were noted in either the erythroid or myeloid mitotic indices of bone marrow samples. Exposure of pregnant mice to microwave radiation under the conditions of these experiments had no effects on the investigated aspects of hematopoiesis.

Teratogenic, biochemical, and histological studies with mice prenatally exposed to 2.45-GHz microwave radiation.

Pregnant CD-1 mice were exposed to 2.45-GHz continuous wave microwave radiation at an incident power density of 30 mW/cm2. The local specific absorption rate near the uterine area (deep colonic location), as determined from time-temperature profiles measured with a Vitek thermistor probe, was 40.2 mW/g. Groups of mice were exposed 8 hr per day through Days 1-6 or 6-15 of pregnancy. Other groups of animals were exposed to an elevated ambient temperature of 31 degrees C which increased the colonic temperature 2.3 degrees C, the same as that produced by the microwaves. Sham-irradiated groups of animals were treated exactly the same as the microwave-exposed animals. For the two conditions, temperature exposed and sham exposed, two groups of animals were used. One group was handled in the same manner as the microwave-irradiated group and the other group was not handled so as to evaluate the effects of stressing the animals by handling. Eleven groups of animals were used in the complete study: five groups for gestational Days 1-6, five groups for gestational Days 6-15, and one group of cage control animals. On Day 18 of gestation the dams of all experimental groups were sacrificed and their reproductive status was determined. The fetuses were examined for visceral and skeletal alterations. Brain cholinesterase activity and histology were evaluated in the groups exposed on Days 6-15. The results show that microwave radiation increases embryo lethality at the early stages of gestation (exposure Days 1-6). Fetal toxicity and teratogenicity were not significantly increased by exposure to microwaves on either Days 1-6 or 6-15 of gestation. Cholinesterase activity and histology of the brain of 18-day-old fetuses were not adversely affected.

Evaluation of in vitro effects of 50 and 60 Hz magnetic fields in regional EMF exposure facilities.

A weak association between magnetic-field exposure and increased incidences of cancer has been reported. While alterations in cellular processes after in vitro magnetic-field exposures have also been reported to provide plausibility for this association, other laboratories have been unable to repeat the findings. As part of an accelerated electric- and magnetic-field (EMF) research program, the National Institute of Environmental Health Sciences with the Department of Energy identified the replication of the published positive effects as a priority. Regional EMF exposure facilities were established to investigate major in vitro effects from the literature. These included effects on gene expression, intracellular calcium, colony growth in soft agar, and ornithine decarboxylase activity. The laboratories that first reported these effects provided experimental protocols, cell lines, and other relevant experiment details. Regional facility studies included sham/sham exposures (no applied field in either chamber) and were done in a blinded fashion to minimize investigator bias. In nearly all experiments, no effects of magnetic-field exposure were found. The effort provided insight into dealing with the difficulty of replication of subtle effects in complex biological systems. Experimental techniques provided some clues for the differences in experimental results between the regional facility and the original investigator. Studies of subtle effects require extraordinary efforts to confirm that the effect can be attributed to the applied exposure.

Conceptualization of conscience in normal children and adolescents, ages 5 to 17.

In order to determine how normal children and adolescents conceptualize their conscience, the Stilwell Conscience Interview was given to 125 normal subjects between the ages of 5 and 17. Responses to questions 1, 2 and 11 (including the drawing of conscience) were empirically analyzed, resulting in a five-stage developmental model. The responses were then randomly presented to two blinded raters to assign them to one of the five stages. Highly acceptable interrater reliability was found, Kappa = 0.90. The relationship of age to stage demonstrated a highly significant positive correlation, indicating that the conceptualization of conscience in normal development follows an invariant, hierarchical pattern of organization. A commentary regarding each stage is presented. The value of this conceptualization model as a comparative standard of normality in the clinical assessment of youngsters suffering from psychopathology is discussed relative to assessment, psychotherapy, and future research.

Moral-emotional responsiveness: a two-factor domain of conscience functioning.

OBJECTIVE: The purpose of this study was to assess the progression in development of moral-emotional responsiveness in children and adolescents and to examine the relationship of this progression with previously identified stages of conceptualization of conscience. METHOD: Using three semistructured questions from the Stilwell Conscience Interview, 132 normal volunteers between the ages of 5 and 17 years were assessed regarding comprehension of their emotional responses to moral stimuli. RESULTS: Rational analysis of the responses identified six items; each item was scaled for complexity into five stages. Factor analysis of the six items revealed two factors: moral-emotional responsiveness 1 contained items relating to external anxiety, internal anxiety, and mood; more-emotional responsiveness 2 contained items relating to the restoration of psychophysiological equilibrium through the processes of reparation and healing. Differences between conceptualization stages, with the moral-emotional responsiveness factors serving as dependent variables, were accounted for by stage differences in age and the positive correlations between the moral-emotional responsiveness factors and age. CONCLUSIONS: Moral-emotional responsiveness is a two-factor domain of the conscience. The findings provide additional developmental guidelines for assessing conscience development and functioning both in clinical practice and in research.

Moral valuation: a third domain of conscience functioning.

OBJECTIVE: To assess development of moral valuation in normal children and adolescents, that is, how moral rules for living are derived and justified, and to examine the relationship of this progression with previously identified stages of conceptualization of conscience. METHOD: Using three semistructured questions from the Stilwell Conscience Interview, 132 normal volunteers between the ages of 5 and 17 years were assessed. All moral valuation responses were examined within three aspects of social reference: authority-derived, self-derived, and peer-derived. Each aspect was scaled for complexity into six anchored levels. RESULTS: The levels of all three aspects correlated positively with conceptualization stages as well as with each other. When the covariate, age, was taken into consideration, peer-derived valuation was significantly correlated with both age and stage. CONCLUSIONS: Moral valuation is a domain of conscience functioning in which moral rules and their justifications are socially referenced in relationship to authority, self, and peers. Anchored levels of these three aspects of moral valuation provide developmental guidelines for mental status examinations in patients between 5 and 17 years of age as well as providing criteria for future comparative studies in various diagnostic categories of psychopathology.

Moralization of attachment: a fourth domain of conscience functioning.

OBJECTIVES: To define discrete developmental levels of understanding regarding the ways in which normal children and adolescents link remembered and current attachment experiences to their moral belief system and to study the correlation between this progression and previously identified stages of conscience conceptualization. METHOD: Using the moralization of attachment section from the semistructured Stilwell Conscience Interview, 132 normal volunteers between the ages of 5 and 17 years were individually interviewed. Analysis of the interviews resulted in five levels of understanding. RESULTS: By analyses of variance and covariance, the five attachment levels showed significant correlation with the five conceptualization stages. Conceptualization stage showed a stronger correlation than age. CONCLUSIONS: In normal development, moralization of attachment is a domain of conscience functioning which follows a five-level hierarchical developmental progression; first, the child's sense of security and empathic responsiveness become paired with a sense of moral obligation; caretaker rules are then incorporated; an understanding of how empathy modifies strict rule-following develops; idols and ideals are chosen that reflect earlier learning in attachment relationships; finally, a visualization of the self as moral standard-bearer or teacher unfolds.

Moral volition: the fifth and final domain leading to an integrated theory of conscience understanding.

OBJECTIVES: To define discrete developmental levels of understanding of the ways in which normal children and adolescents link autonomy and will to moral obligation and to study the correlation between this progression and previously identified stages of conscience conceptualization. METHOD: One hundred thirty-two normal volunteers between the ages of 5 and 17 years were individually interviewed using the moral volition section of the semistructured Stilwell Conscience Interview. Analysis of the interviews resulted in five levels of understanding of moral self-evaluation and volitionally chosen behavior. RESULTS: Analyses of variance and covariance showed that the five levels of moral volition had significant correlation with five conceptualization stages, with stage criteria showing a stronger correlation than age. Self-identified tasks of oughtness were hierarchically defined beginning with those defining a morality of restraint followed by moralities of mastery/sufficiency, virtuous striving, idealization, and individual responsibility. Perception of increased independence of self in interaction with conscience was noteworthy at stages 4 and 5. CONCLUSIONS: Moral volition is the domain of conscience functioning that defines understanding of moral self-evaluation and volitionally chosen actions; five levels of understanding can be demonstrated in normal children between the ages of 5 and 17 years.