The role of agricultural drainage, storm-events, and natural filtration on the biogeochemical cycling capacity of aquatic and sediment environments in Lake Erie's drainage basin.

Lake Erie is the most at risk of the Great Lakes for degraded water quality due to non-point source pollution caused by agricultural activities in the lake's watershed. The extent and temporal patterns of nutrient loading from these agricultural activities is influenced by the timing of agronomic events, precipitation events, and water flow through areas of natural filtration within the watershed. Downstream impacts of these nutrient loading events may be moderated by the co-loading of functionally relevant biogeochemical cycling microbial communities from agricultural soils. This study quantified loading patterns of these communities from tile drain sources, assessed whether functional communities from agricultural sources influenced downstream microbial functionality, and investigated how distance from agricultural sources, storm events, and areas of natural filtration altered nutrient cycling and nutrient fluxes in aquatic and sediment environments. Water and sediment samples were collected in the Wigle Creek watershed in Ontario, from tile drains through to Lake Erie, from May to November 2021, and microbial nitrogen (N) and phosphorous (P) cycling capacity (quantitative PCR), and nutrient levels were evaluated. Results showed that N and P functional groups were co-loaded with nutrients, with increased loading occurring during storm events and during agricultural activities including fertilization and harvest. Overall functional capacity in the aquatic environment decreased with distance from the agricultural sources and as water transited through natural filtration areas. In contrast, the sediment environment was more resilient to both agricultural disturbances and abiotic factors. This study expands our understanding of when and where different stages of N and P cycling occurs in agriculturally impacted watersheds, and identifies both seasons and regions to target with nutrient mitigation strategies.

The long-term impact of eGFR reporting on referral patterns.

BACKGROUND: The prognostic significance of CKD has driven the widespread introduction of automated estimated glomerular filtration rate (eGFR) reporting, and the incorporation of CKD in the revised Quality Outcomes Framework (QOF) of the General Medical Services (GMS) contract in the U.K. AIMS: To assess the long-term impact of the introduction of these two initiatives, on patient referral numbers to a nephrology service. METHODS: Data was collected on the numbers and basic characteristics of all new patients referred from April 2005 to March 2011, to one NHS Health Board. RESULTS: Introduction of eGFR reporting and CKD QOF domains was associated with a significant increase in the number of referrals, which was sustained. The initiatives also led to a sustained increase in the mean age of the patients at referral, predominantly due to an increase in the age of female patients referred. There was also an increase in the proportion of female patients referred. In the immediate aftermath of the introduction of change there was a transient decrease in the average eGFR at referral, a decrease in age of patients referred with an eGFR <15ml/min and an increase in the eGFR of patients >70yrs of age. CONCLUSIONS: The data demonstrates significant and sustained increase in numbers of referrals. In the short term this was associated with a reduction in referral of elderly patients with stage 5 CKD and an increase in elderly patients with mild renal impairment. In the longer term we saw an increase in referral of an older female population.

An assessment of persistent organic pollutants (POPs) in wild and rope grown blue mussels (Mytilius edulis) from Scottish coastal waters.

Farmed, rope grown mussels (Loch Etive and Loch Ewe, both on the west coast of Scotland) and wild mussels (Straad on the west coast and Shell Bay and Aberdeen Breakwater, both on the east coast of Scotland) were collected on a monthly basis and analysed for persistent organic pollutants (POPs) with the aim of assessing the status of Scottish mussels, with respect to concentrations of POPs, and investigating site-specific and seasonal differences. Samples were analysed for polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs) and chlorobiphenyls (CBs). Total PAH (2- to 6-ring parent and alkylated) concentrations in mussels from three pristine sites (ref. 1: ICES Marine Chemistry Working Group Report 2008, http://www.ices.dk/reports/MHC/2007/MCWG07.pdf) (Loch Etive, Loch Ewe and Straad) were significantly lower than in mussels from sites with greater coastal influences (Aberdeen Breakwater and Shell Bay). Seasonal trends in the PAH concentrations were evident at the pristine sites, with concentrations being significantly higher for samples collected between November and March compared to those collected between April and October. The PAH data was assessed using a recently proposed traffic light system, based on the assessment criteria adopted by OSPAR for use in the 2008 Coordinated Environmental Monitoring Programme (CEMP) assessment. Concentrations were compared to Background Assessment Concentrations (BAC; blue/green transition) and Environmental Assessment Concentrations (EACs; green/red transition). All sites were classed as 'green' for the PAHs analysed, being below EACs, where available. The pristine sites were also below BACs for some PAHs and therefore would be classed as 'blue' for these PAHs. CBs and PBDEs were measured in mussels collected between 2006 and 2008 inclusive. Concentrations for CB and PBDEs were significantly higher in the Aberdeen Breakwater mussels than for all other sites. Concentrations at all sites were low with many congeners being below the detection limits for both contaminant groups. No seasonal trends were observed in the CBs or PBDE concentrations or composition at any of the five sites. The green-red transition (described by the EACpassive) was exceeded for CB118 in mussels from Aberdeen Breakwater and surprisingly at the pristine site of Loch Etive. As such both sites were classed as 'red'. All other ICES7 CBs were below EACs and therefore classed as 'blue' or 'green'.

Renal quality outcomes framework and eGFR: impact on secondary care.

BACKGROUND: The prognostic significance of impaired renal function has driven the need for its early recognition and the widespread introduction of the estimated glomerular filtration rate (eGFR) reporting, and the incorporation of Chronic Kidney Disease (CKD) in the revised Quality Outcomes Framework (QOF) of the General Medical Services (GMS) contract in the UK. AIM: To characterize the effect of these changes on referral numbers and appropriateness to a nephrology service, and the impact of a newly introduced Map of Medicine(R)-based patient care pathway coupled to the systematic screening of all new referrals. METHODS: The study was carried out within a single NHS Trust covering five primary health care Local Health Boards and a population of 560,000. RESULTS: Introduction of eGFR reporting and CKD QOF domains was associated with a rapid 61% increase in new patient referral, and an increase in the mean age of the patients at referral from 63.0 +/- 18.1 to 69.1 +/- 18.5. The referrals did not correlate with the QOF reported prevalence of CKD. Systematic screening of new referrals demonstrated 36% to be either inappropriate or inadequate in terms of clinical information supplied. Introduction of the renal patient care pathway was associated with a fall in both the number of inadequate and total new referrals received. Overall 62% of all primary care practices registered with the Map of Medicine(R) and these sent a higher proportion of appropriate referrals and were less likely to generate referrals with inadequate information. The initiative also enabled managed discharges from secondary to primary care settings, freeing up outpatient capacity. CONCLUSION: The study describes the impact of the introduction eGFR reporting and revision of the GMS contract with Renal QOF, on patient referrals to a nephrology service. In addition, we provide evidence that a new management pathway has helped to regulate and proactively manage the increased demand within the current resources.

Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias.

Somatic mutations in nucleophosmin (NPM1) occur in approximately 35% of adult acute myeloid leukemia (AML). To assess the frequency of NPM1 mutations in pediatric AML, we sequenced NPM1 in the diagnostic blasts from 93 pediatric AML patients. Six cases harbored NPM1 mutations, with each case lacking common cytogenetic abnormalities. To explore the phenotype of the AMLs with NPM1 mutations, gene expression profiles were obtained using Affymetrix U133A microarrays. NPM1 mutations were associated with increased expression of multiple homeobox genes including HOXA9, A10, B2, B6 and MEIS1. As dysregulated homeobox gene expression is also a feature of MLL-rearranged leukemia, the gene expression signatures of NPM1-mutated and MLL-rearranged leukemias were compared. Significant differences were identified between these leukemia subtypes including the expression of different HOX genes, with NPM1-mutated AML showing higher levels of expression of HOXB2, B3, B6 and D4. These results confirm recent reports of perturbed HOX expression in NPM1-mutated adult AML, and provide the first evidence that the NPM1-mutated signature is distinct from MLL-rearranged AML. These findings suggest that mutated NPM1 leads to dysregulated HOX expression via a different mechanism than MLL rearrangement.

Trombiculiasis in the Florida black bear.

We found trombiculid mite (Trombiculidae) infestations in 32 of 101 (32%) freeranging Florida black bears (Ursus americanus floridanus) live-captured or necropsied in Florida from January 1999 to April 2000. Prevalence of chigger infestation was greatest in June with no infestations seen October to March. Chigger infestations were recognized as accumulations of bright orange granular material usually associated with hair shafts. Mites were found in clusters of one to 102 (mean +/- SD = 8.5+/-19.5) and were distributed primarily over the ventral abdomen and thorax, inguinal and axillary regions, and proximal medial aspect of the extremities. Mites were identified as larval Eutrombicula splendens. Cutaneous lesions were seen in two of 32 (6%) infested bears.

Congenital mastocytomas in a Holstein calf.

Congenital defects occur infrequently in cattle. In this report, a stillborn Holstein calf was presented for unusual nodules in the skin. Necropsy and histopathologic findings aided in the diagnosis of systemic mastocytoma, or mast cell tumor. The diagnosis of congenital mastocytoma in this case is extremely rare and unique.

Magnetic resonance imaging of spongy degeneration of the central nervous system in a Labrador Retriever.

A 7-month-old, neutered female Labrador Retriever was evaluated for tetraparesis and subtle cerebellar dysfunction. Clinical signs progressed over a period of 6 weeks to severe ataxia, hypermetria, intention tremors, and finally non-ambulatory tetraparesis. On magnetic resonance imaging of the brain there were large, bilaterally symmetrical, ovoid lesions in the region of the deep cerebellar nuclei that were hyperintense on T2-weighted and proton density images and hypointense on T1-weighted images. There were similar but smaller bilaterally symmetrical lesions present within the thalamus. Euthanasia was performed and lesions consistent with the previously described spongy degeneration of Labrador Retrievers were identified. This disease and its relation to similar human heritable leukodystrophies are discussed.

Hypercalcemia in a dog: a challenging case.

An 18-month-old, spayed female, mixed-breed dog was referred for investigation of persistent hypercalcemia. After extensive diagnostic evaluation, a tentative diagnosis of occult lymphosarcoma (LSA) was made and the dog was euthanized. At necropsy, infection with Heterobilharzia americana was diagnosed. In endemic areas, schistosomiasis should be included in the differential diagnosis of hypercalcemia, and a fecal examination should be performed in every dog with a hypercalcemia of unknown origin.

Replication of clinical innovations in multiple medical practices.

BACKGROUND: Many clinical innovations had been successfully developed and piloted in individual medical practice units of Kaiser Permanente in North Carolina during 1995 and 1996. Difficulty in replicating these clinical innovations consistently throughout all 21 medical practice units led to development of the interdisciplinary Clinical Innovation Implementation Team, which was formed by using existing resources from various departments across the region. REPLICATION MODEL: Based on a model of transfer of best practices, the implementation team developed a process and tools (master schedule and activity matrix) to quickly replicate successful pilot projects throughout all medical practice units. The process involved the following steps: identifying a practice and delineating its characteristics and measures (source identification); identifying a team to receive the (new) practice; piloting the practice; and standardizing, including the incorporation of learnings. The model includes the following components for each innovation: sending and receiving teams, an innovation coordinator role, an innovation expert role, a location expert role, a master schedule, and a project activity matrix. Communication depended on a partnership among the location experts (local knowledge and credibility), the innovation coordinator (process expertise), and the innovation experts (content expertise). RESULTS: Results after 12 months of working with the 21 medical practice units include integration of diabetes care team services into the practices, training of more than 120 providers in the use of personal computers and an icon-based clinical information system, and integration of a planwide self-care program into the medical practices--all with measurable improved outcomes. CONCLUSION: The model for sequential replication and the implementation team structure and function should be successful in other organizational settings.

Quantitative DNA ploidy analysis of breast carcinoma: a study of the effects of joint photographer experts group (JPEG) compression on DNA ploidy images.

Telepathology usage in the past has typically been a qualitative procedure rather than a quantitative measurement. DNA ploidy using image analysis has been favorably compared to DNA ploidy analysis by flow cytometry in numerous publications. A step from DNA ploidy analysis using conventional image analysis to DNA ploidy analysis using stored images allows DNA ploidy analysis by image cytometry to become a powerful tool in telepathology. Remote DNA ploidy analysis using stored images has an impact on the field of pathology, as not every hospital or laboratory can afford to perform this type of specialized testing. However, images have large data files and require lengthy transmission times over communication systems to other computers. Joint Photographer Experts Group (JPEG) compression is a computer algorithm that allows the file size of an image to be reduced in order to decrease transmission times to another computer. A study was initiated to investigate the effects of JPEG compression on images of Feulgen stained breast tumor touch preps and the resulting DNA ploidy histograms.

Affective correlates of alcohol and cocaine use.

The affective correlates of alcohol and cocaine use were investigated in two studies. In the first, alcoholics (n = 50) and cocaine addicts (n = 40) were administered factor scales from the Inventory of Drinking Situations as well as the General Temperament Survey. Substance use in negative affect states was reported more often by alcoholics than by cocaine addicts, even when age and race differences were statistically controlled. Alcoholics also reported higher levels of negative temperament, and substance use in negative affect states was correlated with negative temperament across groups. In a study using subjects dependent on both drugs (n = 21), alcohol was more likely to be used in negative affect situations than was cocaine. Thus, the affective correlates of substance use are associated with both individual differences and drug-specific effects. Possible reasons for the differential association of alcohol with negative affect are proposed.

Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3.

Experiments using recombinant vaccinia viruses expressing rat proinsulin I coinfected into COS-7 cells with recombinant vaccinia virus expressing human furin, human PC2, mouse PC3 (subtilisin-related proprotein convertases 1-3, respectively), or yeast Kex2 indicate that in this system both Kex2 and furin produce mature insulin, whereas PC2 selectively cleaves proinsulin at the C-peptide-A-chain junction. This is a property consistent with its probable identity with the rat insulinoma granule type II proinsulin processing activity as described by Davidson et al. [Davidson, H. W., Rhodes, C. J. & Hutton, J. C. (1988) Nature (London) 333, 93-96]. PC3 generates mature insulin but cleaves preferentially at the proinsulin B-chain-C-peptide junction. This pattern of cleavage by PC3 is similar, but not identical, to that of the highly B-chain-C-peptide junction-selective type I activity as described by Davidson et al., perhaps due to the presence of a P4 arginine residue near the C-peptide-A-chain junction unique to the rat proinsulins. These results along with data presented on the expression of both PC2 and PC3 in islet beta cells strongly support the conclusion that these proteases are involved in the conversion of proinsulin to insulin in vivo.

Intrafamilial phenotypic expression of autosomal dominant polycystic kidney disease.

It has been suggested that the clinical expression of autosomal dominant polycystic kidney disease (ADPKD) is uniform among individuals of a given family. To test this hypothesis, intrafamilial variations in ages at onset of first symptoms, types of first symptoms, serum creatinine concentrations, and renal sizes were evaluated in 131 patients with ADPKD from 36 unrelated families. These parameters were compared in younger and older affected relatives in the same family at a single time, due to difficulties of following them longitudinally. Because the natural course of the disease is to progress with age, it was presumed that disease progression in a given family was nonuniform if older individuals had lower serum creatinine concentrations, and/or smaller kidneys than their affected younger relatives, or if relatives of similar ages had different serum creatinine concentrations and/or kidney sizes. Nonuniform progression was suggested in 38% of affected relatives by serum creatinine concentrations and in 53% by kidney sizes. Ages at onset of first symptoms and types of first symptoms were also different in patients from the same families. These data indicate that phenotypic expression of ADPKD may differ considerably among patients who belong to the same families.

Clinical manifestations of autosomal dominant polycystic kidney disease in patients older than 50 years.

The purpose of this study was to define manifestations of autosomal dominant polycystic kidney disease (ADPKD) in older patients with the disease. Fifty-seven subjects age 50 years or more, who were at risk for having inherited the gene for ADPKD, were evaluated for renal size, hypertension, back and abdominal pain, symptoms consistent with urinary tract infection (UTI), hematuria, end-stage renal failure, and liver cysts. The diagnosis of ADPKD was made in 32 of the 57 at-risk subjects (56%). At the time of study, only one patient with the disease was asymptomatic and normotensive and denied any previous symptoms suggestive of the disease. Clinical manifestations of ADPKD in the 31 symptomatic patients were hypertension (69%), a history of back and abdominal pain (47%), symptoms consistent with UTI (41%), hematuria (31%), and end-stage renal failure (47%). Liver cysts were found in 44% of patients. No statistically significant differences in the frequency of any manifestations of ADPKD between men and women were found, although the frequency of symptoms consistent with UTI tended to be higher in women (53%) than in men (27%). Most patients developed symptoms after the age of 40 years. Notably, 31% of the older patients with ADPKD had normal serum creatinine levels. Thus, older subjects with kidney cysts who are at risk to have inherited the gene for ADPKD, should be considered to have the disease even in the presence of well-preserved kidney function. This observation may play an important role in assessing the prognosis of older subjects at risk who have bilateral renal cysts and in genetic counseling of their relatives.

Radiologic assessment of head trauma.

We have endeavored through the use of an actual clinical scenario to emphasize that reliance on skull radiographs for assessing the acutely traumatized patient is both unwarranted and unwise. Not only are these films fundamentally useless, but they have the potential to lull us into a false sense of security. A negative skull examination cannot and does not imply that the brain substance is normal. If there is a legitimate indication for any examination, that examination should be computed tomography. To reinforce this notion, we offer for your consideration the following algorithm for the management of head trauma (Table 1: see text).

Autosomal dominant polycystic kidney disease: symptoms and clinical findings.

In 259 subjects at risk to have inherited autosomal dominant polycystic kidney disease (PKD), the frequency of symptoms consistent with urinary tract infection, haematuria, back and abdominal pain, hypertension, renal stones, and end-stage renal failure was evaluated. The diagnosis of PKD was made in 140 of these subjects (54 per cent). At the time of the study, 36 per cent of males and 7 per cent of females with PKD were asymptomatic, normotensive, and denied any previous problems. In patients younger than 30 years, 66 per cent of males but only 11 per cent of females were asymptomatic. In female patients, urinary tract infection (69 per cent) and hypertension (61 per cent) were the most frequent clinical manifestations. In contrast, in males with PKD, these problems were present in only 19 per cent and 42 per cent, respectively. Frequency of other clinical manifestations was similar in women and men with PKD. End-stage renal failure was present in 5 per cent of the 81 patients younger than age of 40, in 33 per cent of the 27 patients 40-49 years old, and in 47 per cent of the 32 patients aged 50 years or more. Physical examination was unreliable in estimating kidney size in most patients, particularly in early stages of the disease. Hypertension and symptoms such as haematuria and back pain, but not urinary tract infections, correlated well with renal size measured by radiograms.

Fertility and pregnancy complications in women with autosomal dominant polycystic kidney disease.

Fertility and pregnancy complications were assessed in 137 women at risk of having inherited the gene for autosomal dominant polycystic kidney disease. Seventy-six (55%) of these subjects were found to have polycystic kidney disease (multiple renal cysts). The remaining 61 women served as controls. The prevalence of fertility, spontaneous abortion, stillbirth, and symptoms consistent with urinary tract infection were not different in the two groups. However, the frequency of hypertension first diagnosed during pregnancy (with or without preeclampsia or eclampsia) and the frequency of pregnancy-unrelated hypertension were higher in women with polycystic kidney disease. No evidence was found that pregnancy had an adverse effect on the natural course of polycystic kidney disease. The incidence of renal failure was not higher in women with polycystic kidney disease who had three or more pregnancies than in women of similar ages who had two, one, or no pregnancies.