Lung nodules are reliably detectable on ultra-low-dose CT utilising model-based iterative reconstruction with radiation equivalent to plain radiography.

AIM: To determine if ultra-low-dose (ULD) computed tomography (CT) utilising model-based iterative reconstruction (MBIR) with radiation equivalent to plain radiography allows the detection of lung nodules. MATERIALS AND METHODS: Ninety-nine individuals undergoing surveillance of solid pulmonary nodules undertook a low-dose (LD) and ULD CT during the same sitting. Image pairs were read blinded, in random order, and independently by two experienced thoracic radiologists. With LD-CT as the reference standard, the number, size, and location of nodules was compared, and inter-rater agreement was established. RESULTS: There was very good inter-rater agreement with regards nodules ≥4mm for both the LD- (k=0.931) and ULD-CT (k=0.869). One hundred and ninety-nine nodules were reported on the LD-CT by both radiologists and 196 reported on the ULD-CT, with no nodules reported only on the ULD-CT. This gives a sensitivity of 98.5% and specificity of 100% for ULD-CT with MBIR. The effective dose of radiation was significantly different between the two scans (p<0.0001), 1.67 mSv for the LD-CT and 0.13 mSv for the ULD-CT. CONCLUSION: ULD-CT utilising MBIR and delivering radiation equivalent to plain radiography, allows detection of lung nodules with high sensitivity. The attendant 10-fold reduction in radiation may allow for dramatic reductions in cumulative radiation exposure.

Family impact of childhood neurodevelopmental disability: considering adaptive and maladaptive behaviour.

BACKGROUND: The aim of the current study was to identify functional predictors of perceived impact of childhood disability among families of children with neurodevelopmental disorders and disabilities. We first examined the relationship between sub-domains of adaptive and problematic behaviour and perceived family impact. Second, we examined whether the same sub-domains would emerge as significant after controlling for the impact of child diagnosis, including autism spectrum disorder, cerebral palsy and intellectual disability. METHOD: Caregivers of 216 children and adolescents (M = 8.17 years) with neurodevelopmental disorder and disability completed measures of children's practical, conceptual and social skills (i.e. adaptive behaviour), behaviour problems and positive and negative family impact. RESULTS: Indices of child adaptive and problematic behaviour were only significantly associated with perceived negative family impact. Children's practical and social skills, as well as emotional symptoms, emerged as significant predictors of perceived negative family impact, with emotional symptoms accounting for greatest variance. Including diagnosis in our statistical models did not explain additional variance above and beyond these particular sub-domains of child functioning. CONCLUSIONS: The study findings suggest that it is not children's most impaired domains of functioning that are perceived as significantly impactful by the family. The findings highlight the importance of devoting consideration to the ways in which the functional limitations experienced by children with chronic developmental health conditions similarly impact family life and well-being, regardless of disorder designation.

North Central Asia isotopic database for archaeological samples.

The North Central Asia Isotopic Database (NCAID) is an open-access dataset of stable isotope measurements from archaeological remains, spanning from the Early Neolithic until present-day in North Central Asia. With 3,143 individual entries corresponding to data accumulated over more than 20 years of research, this comprehensive dataset encompasses measurements of stable carbon and nitrogen isotopes in organic fractions from archaeological humans, animals, and plants. NCAID incorporates diverse supporting information, providing geographical information, archaeological context descriptions, and chronology. This resource facilitates research into past human lifeways, paleo-environments/climates, and animal management practices throughout North Central Asia and will be continually updated as more novel data is released.

Diagnostic nomenclature for foetal alcohol spectrum disorders: the continuing challenge of causality.

Prenatal alcohol exposure is a risk factor for neurologically based cognitive and adaptive disability. Diagnostic nomenclature for prenatally exposed children with cognitive and adaptive disability who lack features for foetal alcohol syndrome (FAS) or partial FAS includes the terms alcohol-related neurodevelopmental disorder (ARND) and foetal alcohol spectrum disorder(s) (FASD). Although these terms are now widely used, this paper argues that both are problematic. ARND is flawed by unjustifiably turning a risk factor into a causal factor and shrouding the result in terminological ambiguity, while FASD is not appropriate as a clinical label, and its use as a proxy for ARND deflects critical attention from the causal inferencing that is integral to diagnosing children with an alcohol-related teratogenic condition. Existing nomenclature is at odds with logical and evidence-based diagnosing and also has implications for interpretation of epidemiological data. Diagnostic nomenclature that is not tightly linked to causal inference is preferable at the present stage of this field's development.

Initial findings: primary diabetes care responsibility among emerging adults with type 1 diabetes post high school and move out of parental home.

BACKGROUND: Emerging adults with diabetes are assuming diabetes care responsibility, graduating from high school and leaving their parental homes. We examined: (1) how diabetes care responsibility changed in relation to time (high school to post high school) and living situation (living independently or not of parents) and (2) the association of diabetes self-efficacy, worry about hypoglycaemia, gender and glycaemic control with these changes in responsibility among emerging adults with type 1 diabetes. METHODS: During the last 6 months in high school (T1), 113 participants completed diabetes care responsibility (total, daily and non-daily), diabetes self-efficacy and worry about hypoglycaemia scales. Participants again completed the responsibility scales post high school graduation (T2). We used a linear mixed-effects model with diabetes self-efficacy, worry about hypoglycaemia, time since graduation, living situation, gender and glycaemic control as independent variables; and diabetes care responsibility (total, daily and non-daily) as dependent variables. Moderation involving diabetes self-efficacy, worry about hypoglycaemia, gender and glycaemic control was also tested. FINDINGS: Diabetes care responsibility increased over time for total (P < 0.001), daily (P= 0.002) and non-daily (P < 0.001), but the associations of self-efficacy and gender with diabetes care responsibility were moderated by living situation. Self-efficacy was negatively related to total (P= 0.006), daily (P= 0.010) and non-daily (P= 0.030) responsibility for those not living independently while positively related only to total responsibility (P= 0.028) for those living independently. Being female was positively related to total (P= 0.007) and non-daily (P= 0.001) responsibility for those living independently. CONCLUSION: Diabetes care responsibility increased from high school to post high school among these emerging adults with diabetes. There is a complex relationship between self-efficacy, gender and responsibility related to living independently of parents for these youth.

Mini-nutrition assessment, malnutrition, and postoperative complications in elderly Chinese patients with lung cancer.

PURPOSE: To assist healthcare professionals in using the mini nutrition assessment (MNA) and its short-form (MNASF) for early identification of malnourished elderly lung cancer patients, conducting preoperative nutritional support, and improving patients' postoperative prognosis, quality of life, and survival. METHODS: The MNA with revised cut-off points to better suit the Chinese population was conducted on 103 elderly lung cancer Chinese patients aged 60 or above in the Tianjin Cancer Hospital prior to their scheduled surgery. Patient demographic data, anthropometric parameters, biochemical markers, and postoperative complications were collected and analysed. RESULTS: Of the 103 patients studied 12.6% (13/103) were malnourished, 31.1% (32/103) were at risk of malnutrition, and 56.3% (58/103) had adequate nutrition; the average MNA score was 23.6±3.7. Significant positive correlations were found between total MNA score and body mass index (BMI), mid-arm circumference (MAC), calf circumference (CC), and hemoglobin (Hb) (p<0.05), as well as between total MNA-SF score and BMI, MAC, CC, and total MNA score. Significant negative correlations occurred between total MNA-SF score and age (p<0.05). Among postoperative complications, cardiovascular diseases had the highest morbidity rate (23%), followed by respiratory diseases (22%), and cardiovascular and respiratory diseases combined (19%). No significant relationship between nutritional status with types of morbidity (p=0.235) and postoperative complications (p=0.362) was found. CONCLUSION: The MNA scale is an effective tool to preoperatively evaluate the nutritional status of elderly Chinese patients with lung cancer. These patients have poor nutritional status. Further investigations are needed to re-examine the correlation between the MNA results and postoperative complications.

Insulin dose changes in children attending a residential diabetes camp.

AIMS: To examine the effects of insulin dose adjustments on rates of hypoglycaemia for school-aged children with Type 1 diabetes attending camp. METHODS: Camp records for 256 children aged 7-15 years (55% on continuous subcutaneous insulin infusion) attending a week-long residential summer camp were analysed. RESULTS: In anticipation of increased physical activity, basal insulin was decreased for all children on continuous subcutaneous insulin infusion and injection therapy by 10% upon arrival at camp. During the first day, children on continuous subcutaneous insulin infusion received 11.1±6.3% less basal insulin than home doses, whereas children on injections decreased intermediate/long-acting insulin by 8.2±12.8%. Despite these decreases, 60% had at least one blood sugar level <70 mg/dl (3.9 mmol/l) during the first day. Children on continuous subcutaneous insulin infusion were more likely to have hypoglycaemia during the first day than those on injections. The number of episodes of hypoglycaemia increased with increasing camper age. Overall, children did not have further significant reductions in their total daily insulin dose by the last day of camp. However, on the last day, children had fewer episodes of hypoglycaemia than during the first day (0.7±0.9 vs. 1.1±1.2, P<0.001) and 51% had no low blood sugar levels that day. CONCLUSIONS: An empiric 10% reduction in basal insulin appears reasonable, as nearly equal numbers of children required dose increases as dose decreases as camp progressed. However, hypoglycaemia was still common in all age groups. Prospective studies characterizing individual variables are needed in order to facilitate tailored insulin dose adjustments that minimize glycaemic variability while optimizing control in the diabetes camp setting.

Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model.

The in vivo efficacy of terbinafine was compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Topical antifungal treatment commenced three days post-infection, and each agent was applied once daily for seven consecutive days. Upon completion of the treatment period, evaluations of clinical and mycological efficacies were performed, as was scanning electron microscopy (SEM) analyses. Data showed that while all tested antifungals demonstrated significant mycological efficacy in terms of eradicating the fungi over untreated control, terbinafine and luliconazole showed superior clinical efficacy compared to lanoconazole (P-values < 0.001 & 0.003, respectively). Terbinafine demonstrated the highest clinical percent efficacy. SEM analysis revealed hairs from terbinafine and lanoconazole-treated animals had near complete clearance of fungi, while samples from luliconazole-treated animals were covered with debris and few conidia. This study demonstrates that, in general, terbinafine possessed similar efficacy to lanoconazole and luliconazole in the treatment of dermatophytosis. Terbinafine tended to have superior clinical efficacy compared to the azoles tested, although this difference was not statistically significant against luliconazole. This apparent superiority may be due to the fungicidal activity of terbinafine compared to the fungistatic effect of the other two drugs.

The earliest domestic cat on the Silk Road.

We present the earliest evidence for domestic cat (Felis catus L., 1758) from Kazakhstan, found as a well preserved skeleton with extensive osteological pathologies dating to 775-940 cal CE from the early medieval city of Dzhankent, Kazakhstan. This urban settlement was located on the intersection of the northern Silk Road route which linked the cities of Khorezm in the south to the trading settlements in the Volga region to the north and was known in the tenth century CE as the capital of the nomad Oghuz. The presence of this domestic cat, presented here as an osteobiography using a combination of zooarchaeological, genetic, and isotopic data, provides proxy evidence for a fundamental shift in the nature of human-animal relationships within a previously pastoral region. This illustrates the broader social, cultural, and economic changes occurring within the context of rapid urbanisation during the early medieval period along the Silk Road.

Fission-fragment synthesis of a new nitrogen-fluorine compound.

Fission-fragment radiolysis of a mixture of NF(3) and F(2) at room temperature has resulted in the formation of a new, unidentified nitrogen fluorine compound that is stable at room temperature.

The clinical impact of nucleic acid amplification tests on the diagnosis and management of tuberculosis in a British hospital.

BACKGROUND: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines. METHODS: A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. RESULTS: Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. CONCLUSIONS: There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.

Cytomegalovirus retinitis in the absence of HIV or immunosuppression.

PURPOSE: Cytomegalovirus (CMV) retinitis classically occurs in advanced human immunodeficiencyvirus (HIV) infection but is rare in other forms of immunosuppression. The authors report a case of CMV retinitis in an HIV-negative man with idiopathic CD4 lymphocytopenia (ICL). This is the first such case to be confirmed by polymerase chain reaction (PCR) of aqueous humor. METHODS: Case report. RESULTS: A 69-year-old retired Chinese seaman presented with gradual visual deterioration. He was a diet controlled diabetic on regular steroids for presumed asthma. Examination showed no diabetic eye disease but confirmed acute retinal necrosis (ARN). Anterior chamber tapping of the aqueous humor was PCR positive for CMV. HIV antibody and RNA tests were negative but his full blood count revealed lymphocytopenia, with a low CD4+ subset. He responded to a 3-week course of intravenous ganciclovir therapy followed by suppressiveoral valganciclovir. CONCLUSIONS: CMV is associated with sight-threatening retinitis in HIV infection at CD4+ counts below 50 cells/microL and in transplant recipients or heavily immunosuppressed patients. Systemic steroids are a risk factor for clinical disease in these groups. It is extremely rare to report CMV eye disease in previously healthy individuals. This case illustrates that the condition does occur in association with ICL. Corticosteroids may be implicated in disease reactivation. Molecular METHODS are necessary to confirm the diagnosis.

Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma.

A 49-year-old patient with primary, recurrent melanoma on the lower extremity developed metastatic leptomeningeal melanoma that did not respond to treatment with radiation therapy or intrathecal interleukin 2 (IL-2). Disease was characterized by neurological symptoms, including loss of hearing, loss of short-term memory, and gait disturbance. CD8+ CTLs were generated in vitro using autologous dendritic cells pulsed with peptides from the melanoma-associated antigens tyrosinase (145-156), Melan-A/MART-1 (26-35), and gp100/Pmel 17 (209-217). The CTLs exhibited up to 74% specific lysis against peptide-pulsed autologous EBV-transformed B cells, with Melan-A-specific CTLs yielding the greatest lytic activity. CD8+ CTLs possessed a type 1 cytokine profile, expressing tumor necrosis factor alpha and IFNgamma but not IL-4. Infusions of CTLs were supported with systemic low-dose IL-2 administration. 111In labeling and computerized gamma imaging were used to monitor the distribution of CTLs up to 48 h after infusion. Intra-arterial delivery via the right carotid artery was followed by redistribution of the CTLs to the lungs, liver, and spleen within 16 h. In contrast, delivery via an indwelling Ommaya reservoir resulted in prolonged retention of CTLs within the brain for at least 48 h after infusion. Marked but transient elevations in tumor necrosis factor alpha, IFN-gamma, and IL-6 in the cerebrospinal fluid were observed within 4 h of CTL infusion. There was no evidence of tumor progression throughout the treatment period, and clinically the patient showed some resolution of neurological symptoms.

Autonomic denervation in jejunal mucosa of homosexual men infected with HIV.

Autonomic nerves in jejunal mucosa of HIV-infected patients show severe structural damage on electron microscopic examination. The aim of this study was to quantify loss of autonomic axons from the lamina propria of HIV-infected patients in different clinical stages of disease. Jejunal biopsies were taken from 19 HIV-antibody-positive homosexual men and from 10 control patients. Autonomic fibres in the mucosa were stained with a neurone-specific polyclonal antibody, PGP 9.5. The density of axons was quantified by a point-counting technique using a Lennox eyepiece graticule under light microscopic examination. There was significant reduction in axonal density in the villi of HIV-infected patients [mean, 9.0; standard deviation (s.d.), 4.7] compared with controls (mean, 15.3; s.d., 5.2; P = 0.003), and in the pericryptal lamina propria of HIV-infected patients (mean, 17.8; s.d., 5.4) compared with controls (mean, 27.3; s.d., 6.2; P = 0.0002). Although autonomic denervation occurs throughout the jejunal mucosa of HIV-infected patients, there was no correlation between the clinical stage of HIV disease and the degree of denervation. The denervation was greatest in patients with the most severe diarrhoea, but this difference was not significant. This study provides the first quantitative morphological evidence for depletion of autonomic nerves in the jejunum of patients infected with HIV. Autonomic neuropathy may contribute to chronic diarrhoea in HIV disease.

Simultaneous use of two retroviral vectors in human gene marking trials: feasibility and potential applications.

Two Moloney murine leukemia virus (Mo-MLV)-based neoR retroviral vectors--LNL6 and G1Na--were used to transduce various human tumor-infiltrating lymphocytes (TIL) populations. These groups included bulk CD(8+)- and CD(4+)-enriched TIL from human renal cell carcinomas and melanomas. Transduction efficiencies averaged 5% for single 4-hr supernatant infections. Integrated provirus could be detected for up to 4 weeks of in vitro culture. LNL6 provirus could be distinguished from G1Na provirus using specific polymerase chain reaction (PCR) primers. A single neomycin phosphotransferase (neoR) gene copy could be detected in 10(5) TIL. Using quantitative PCR, the relative ratio of LNL6 to G1Na copies in the same sample could be determined even at low copy numbers. These preclinical studies demonstrate the feasibility of using two retroviral marking vectors in human gene therapy efforts.

Cytokine priming reduces dependence on TNF-R2 for TNF-alpha-mediated induction of macrophage nitric oxide generation.

In the presence of interferon-gamma (IFN-gamma), human tumor necrosis factor-alpha (Hu-TNF-alpha), which binds to murine TNF-alpha receptor type 1 (TNF-R1) but not to murine TNF-R2, was effective in inducing nitric oxide (NO) production in spleen-derived macrophages (M phi), albeit at concentrations 12.5-fold greater than those required by murine TNF-alpha (Mu-TNF-alpha), to achieve the same result. Addition of anti-TNF-R1 completely inhibited the Mu-TNF-alpha-mediated induction of NO, demonstrating that TNF-R1 is critical to the IFN-gamma-dependent TNF-alpha-mediated induction of M phi effector function. However, treatment with anti-TNF-R2 resulted in a partial inhibition of M phi activation. Spleen-derived M phi were more dependent on TNF-R2 than RAW 264.7 or peritoneal M phi based on their responsiveness to Hu-TNF-alpha. Priming of spleen-derived M phi with either IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF) heightened the maximal responses to both TNF-alpha species and increased the overall effectiveness of Hu-TNF-alpha without increasing expression of either TNF-alpha receptor. The dependence of spleen-derived M phi on both TNF-alpha receptors for signaling the induction of effector function supports an active signaling role for TNF-R2 in its synergy with TNF-R1 rather than a passive ligand passing role.

Multifunctional cytokine expression by human mast cells: regulation by T cell membrane contact and glucocorticoids.

Human mast cells readily release a variety of mediators, including cytokines, in response to IgE receptor crosslinking, but the mechanisms governing the expression of cytokines are still unclear. Using a human mast cell line, HMC-1, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-1 cells expressed transcripts for interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, GM-CSF, and weakly for IL-8, and stimulation with ionomycin and PMA induced additional transcripts for IL-6 and IL-13 and upregulated expression of IL-8 transcripts. HMC-1 cells secreted IL-4, IL-8, and GM-CSF protein after activation and dexamethasone significantly inhibited the production of these cytokines. Of significance is the finding that the addition of membranes purified from activated T cells to mast cell cultures induced transcripts selectively for IL-8 and none for other proinflammatory cytokines. Flow cytometry revealed that resting HMC-1 cells express CD40, a molecule involved in contact-dependent signaling of monocytes and B cells by T cells. However, activation of HMC-1 by anti-CD40 antibody did not induce IL-8 gene expression or protein production. This study demonstrates that human mast cells are capable of expressing multiple cytokines that can be inhibited by glucocorticoids. It also raises the possibility that T cells may activate mast cell cytokine synthesis by novel contact-dependent mechanisms. This phenomenon of T cell regulation of mast cell function requires further study.

The electron spin resonance spectrum of a suicidal fungus.

The electron spin resonance spectrum of a suicidal inositol auxotroph of Neurospora crassa, previously used as a model of cellular aging, exhibits a high-spin Fe(III) signal whose intensity increases as a function of the mutant's "senescence". Surprisingly, the intensity of the signal is further enhanced by the exogenous antioxidant nordihydroguaiaretic acid, which reportedly decreases the rate of senescence.

A computer model of the evolution of specific maximum lifespan.

To answer the question of why organisms have evolved finite and specific maximum lifespans, I have built and experimentally studied a discrete-event simulation model of the evolution of lifespan. Through natural selection, the model evolves an apparent plateau in maximum lifespan, the height of which is a decreasing function of both the intensity of niche fluctuations and specific fecundity. Evolved lifespan is therefore finite (small and essentially constant over accessible time intervals) and specific. Experiments demonstrate that the plateau is not due to group selection. Instead, it occurs because the rate of increase of maximum lifespan by natural selection - in an environment presenting a finite probability that death will occur prior to reaching the genetically specified maximum - is a decreasing function of maximum lifespan itself and asymptotically approaches zero. This supports in part a class of existing hypotheses that finite lifespan is due to an equilibrium between weak selection, as in the model, and various lifespan-decreasing processes, which however were not simulated in the present experiments. Although the model shows that such counter processes are not strictly necessary for the evolution of finite and specific maximum lifespan, my interpretation of the model's correspondence to organic evolution does imply a counter process, a bias in random genetic drift toward shorter lifespan, that is more general than those previously hypothesized.