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.

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.

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.

Mapping genetic modifiers of survival in a mouse model of Dravet syndrome.

Epilepsy is a common neurological disorder affecting approximately 1% of the population. Mutations in voltage-gated sodium channels are responsible for several monogenic epilepsy syndromes. More than 800 mutations in the voltage-gated sodium channel SCN1A have been reported in patients with generalized epilepsy with febrile seizures plus and Dravet syndrome. Heterozygous loss-of-function mutations in SCN1A result in Dravet syndrome, a severe infant-onset epileptic encephalopathy characterized by intractable seizures, developmental delays and increased mortality. A common feature of monogenic epilepsies is variable expressivity among individuals with the same mutation, suggesting that genetic modifiers may influence clinical severity. Mice with heterozygous deletion of Scn1a (Scn1a(+/-) ) model a number of Dravet syndrome features, including spontaneous seizures and premature lethality. Phenotype severity in Scn1a(+/-) mice is strongly dependent on strain background. On the 129S6/SvEvTac strain Scn1a(+/-) mice exhibit no overt phenotype, whereas on the (C57BL/6J × 129S6/SvEvTac)F1 strain Scn1a(+/-) mice exhibit spontaneous seizures and early lethality. To systematically identify loci that influence premature lethality in Scn1a(+/-) mice, we performed genome scans on reciprocal backcrosses. Quantitative trait locus mapping revealed modifier loci on mouse chromosomes 5, 7, 8 and 11. RNA-seq analysis of strain-dependent gene expression, regulation and coding sequence variation provided a list of potential functional candidate genes at each locus. Identification of modifier genes that influence survival in Scn1a(+/-) mice will improve our understanding of the pathophysiology of Dravet syndrome and may suggest novel therapeutic strategies for improved treatment of human patients.

The clinical utility of HIV outpatient pharmacist prescreening to reduce medication error and assess adherence.

Antiretroviral therapy (ART) is complex and has high propensity for medication error and drug-drug interactions (DDIs). We evaluated the clinical utility of pharmacist prescreening for DDIs, adherence to ART and medicines reconciliation prior to HIV outpatient appointments. A pharmacist took detailed medication histories and ART adherence assessments, then screened medication for DDIs. A template detailing current medication, potential DDIs and adherence was filed in the clinical notes and physicians were asked for structured feedback. Potential DDIs were observed in 58% of 200 patients, with 22 (9%) potential DDIs occurring with medication that was not previously recorded in the patients' notes. Of 103 physician responses, 61.2% reported that the pharmacist consultation told them something they did not know, and pharmacist consultants led to change in management in 13.6% of cases. Pharmacist consultations were more likely to add benefit in patients taking two or more concomitant medications in addition to ART (P = 0.0012).

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.

Lyme disease in a British referral clinic.

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. DESIGN: Descriptive study conducted by retrospective casenotes review. METHODS: Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010). RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

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.

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.

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.

A rapid fluorescence-based assay for detecting soluble methane monooxygenase.

A fluorescence-based assay was developed to estimate soluble methane monooxygenase (sMMO) activity in solution. Whole cells of Methylosinus trichosporium OB3b expressing sMMO were used to oxidize various compounds to screen for fluorescent products. Of the 12 compounds tested, only coumarin yielded a fluorescent product. The UV absorbance spectrum of the product matches that of 7-hydroxycoumarin, and this identification was confirmed by 13C-NMR spectroscopy. The dependence of the fluorescent reaction on sMMO activity was investigated by pre-incubation with acetylene, a known inhibitor of sMMO activity. Apparent kinetic parameters for whole cells were determined to be Km(app)=262 microM and Vmax(app)=821 nmol 7-hydroxycoumarin min(-1) mg protein(-1). The rate of coumarin oxidation by sMMO correlates well with those of trichloroethylene degradation and naphthalene oxidation. Advantages of the fluorescence-based coumarin oxidation assay over the naphthalene oxidation assay include a more stable product, direct detection of the product without additional reagents, and greater speed and convenience.

Irofulven (6-hydroxymethylacylfulvene, MGI 114) induces caspase 8 and 9-mediated apoptosis in human pancreatic adenocarcinoma cells.

BACKGROUND: Irofulven (MGI 114) is a novel, clinically active sesquiterpene whose mechanism of action is not fully understood. We sought to identify apoptotic effectors induced by this agent in human pancreatic cancer cells. MATERIALS AND METHODS: MTT assay was used to assess IC50-Apoptosis was quantitated by flow cytometry and DAPI staining. Caspase activation was identified by western blot analysis. RESULTS: Irofulven was cytotoxic against all pancreatic cancer cell lines tested (IC50 1-18 microM), and induced 10-fold (4%+/- 2, vs. 41% +/- 5) induction of apoptosis. Irofulven-treated cells also demonstrated PARP3 cleavage and DAPI staining. Apoptosis was reduced to baseline levels by Z-VAD-FMK, a broad-spectrum caspase inhibitor. Western blot analysis revealed that caspases-3, -7, -8, and -9 were activated by irofulven. Time course evaluation demonstrated that caspases-8 and -9 were the initial species activated. CONCLUSION: Our data demonstrate that the cytotoxicity of irofulven in human pancreatic carcinoma cell lines is mediated by caspase-induced apoptosis.

The association of irritable bowel syndrome and somatization disorder.

BACKGROUND AND OBJECTIVE: Irritable bowel syndrome (IBS) and somatization disorder (SD) are defined by nonobjective symptoms that overlap considerably. Psychiatric symptoms associated with IBS may originate from SD in IBS patients. Previous studies of IBS have not considered SD separately from IBS. METHODS: This study explored psychiatric symptoms and illness behavior in IBS in relation to SD. A total of 50 outpatients with IBS or ulcerative colitis (UC) were evaluated with the Diagnostic Interview Schedule and Illness Behavior Questionnaire. RESULTS: Definite or probable SD was diagnosed in no UC patients and in 42% of IBS patients (confirmed in 25% and lacking one symptom in another 17%). IBS patients with probable or definite SD, but not those without SD, reported more psychiatric symptoms and abnormal illness behaviors than did UC patients. SD accounted for the association of psychiatric symptoms with IBS. CONCLUSIONS: In this university-based office setting, the association of psychiatric features with IBS appears heterogeneous predicated on whether SD is present. Future studies of functional bowel diseases should distinguish between patients with and without SD to clarify its relationship to these disorders. Clinicians should consider whether patients with functional disorders have SD, a diagnosis that indicates specific clinical management strategies.