Geographic and temporal trends in pediatric and young adult brain tumors in Kentucky, 1995-2019.

INTRODUCTION: Pediatric and young adult brain tumors (PYBT) account for a large share of cancer-related morbidity and mortality among children in the United States, but their etiology is not well understood. Previous research suggests the Appalachian region of Kentucky has high rates of PYBT. This study explored PYBT incidence over 25 years in Kentucky to identify geographic and temporal trends and generate hypotheses for future research. METHODS: The Kentucky Cancer Registry contributed data on all PYBT diagnosed among those aged 0-29 during years 1995-2019. Age- and sex-adjusted spatio-temporal scan statistics-one for each type of PYBT, and one for all types-comprised the primary analysis. These results were mapped along with environmental and occupational data. RESULTS: Findings indicated that north-central Kentucky and the Appalachian region experienced higher rates of some PYBT. High rates of astrocytomas were clustered in a north-south strip of central Kentucky toward the end of the study period, while high rates of other specified types of intracranial and intraspinal neoplasms were significantly clustered in eastern Kentucky. The area where these clusters overlapped, in north-central Kentucky, had significantly higher rates of PYBT generally. DISCUSSION: This study demonstrates north-central Kentucky and the Appalachian region experienced higher PYBT risk than the rest of the state. These regions are home to some of Kentucky's signature industries, which should be examined in further research. Future population-based and individual-level studies of genetic factors are needed to explore how the occupations of parents, as well as prenatal and childhood exposures to pesticides and air pollutants, impact PYBT incidence.

Upscaling the remediation of acidic landscapes - the coastal floodplain prioritisation method.

Over 24 million hectares of the world's coastal floodplains are underlain by acid sulfate soils (ASS). Drainage of these sediments has led to widespread environmental degradation, raising serious health concerns. To date, onsite rehabilitation has been complicated by differing stakeholder priorities, with resources often allocated to sites with more vocal proponents rather than those exposed to more significant environmental impacts. To address this issue, this paper introduces the Coastal Floodplain Prioritisation (CFP) Method; a novel, data driven and spatially explicit multi-criteria assessment that ranks floodplain catchment areas according to their risk of transferring acidic drainage waters to an estuary. Results can be used to prioritise where remediation actions are likely to have the greatest benefit. The method was applied across six different estuaries in south-east Australia, with major field campaigns undertaken at each site. Within each estuary, the largest acid fluxes and impacts are identified with relevant mitigation measures provided. On a catchment scale, the results reflect the broader hydrogeomorphic characteristics of each estuary, including the historic acid formation conditions and recent anthropogenic drainage activities. Low-lying backswamps were identified as the highest risk zones within each estuary. These areas are also the most vulnerable to sea level rise. Reinstatement of tidal inundation to these backswamps effectively remediates acid sulfate soil discharges and provides a nature-based solution for adaptation to sea level rise with a range of co-benefits to encourage further investment.

Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

PURPOSE: A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. PATIENTS AND METHODS: A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. RESULTS: A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41-24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). CONCLUSIONS: HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

The utility of lateral neck radiographs in the management of fish bones.

BACKGROUND: Lateral neck radiographs are commonly used in the investigation and management of patients presenting with suspected fish bone impaction. The effectiveness of these is questioned, as many fish do not have radio-opaque bones. OBJECTIVE: This study evaluated the utility of lateral neck radiographs in the management of patients presenting with fish bones retained in the upper aerodigestive tract, with the creation of a treatment algorithm to guide further management. METHODS: An audit of practice was undertaken at the University Hospital of Southampton, identifying all patients admitted with potential fish bone impaction in the upper aerodigestive tract. Following analysis, a treatment algorithm was constructed for use by junior doctors. RESULTS: In total, 34 per cent of patients with a normal radiograph were subsequently found to have a fish bone present under local or general anaesthetic assessment. The sensitivity of radiographs in the detection of fish bones was found to be 51.6 per cent. CONCLUSION: Lateral neck radiographs have limited value in the management of suspected fish bone impaction, and should only be used following detailed clinical examination of the upper aerodigestive tract.

A five-year follow-up observational study of the T-14 paediatric throat disorders outcome measure in tonsillectomy and adenotonsillectomy.

INTRODUCTION: The T-14 questionnaire is a validated outcome measurement tool to assess the value of paediatric tonsillectomy from a parent's perspective. There is a paucity of data regarding the long-term postoperative effects of tonsillectomy on quality of life in the paediatric population. Our previous study assessed T-14 scores up to year 2 postoperatively, with this study extending follow-up to 5 years. MATERIALS AND METHODS: We undertook a prospective uncontrolled observational study examining 54 paediatric patients undergoing tonsillectomy at Portsmouth Hospitals NHS Trust. Parents of children undergoing surgery were invited to complete a T-14 questionnaire preoperatively, as well as at 3 months, 6 months, 1 year, 2 years and now 5 years postoperatively. RESULTS: In total, 44 of 54 patients completed questionnaires preoperatively and at all postoperative time points, with 46 being completed at 5 years. There was a highly significant (P < 0.001) difference between the preoperative scores and all other measured T-14 scores postoperatively. The mean score preoperatively was 33.3 compared with 1.0 at 5 years. CONCLUSIONS: This is the first study to assess long-term quality of life following paediatric tonsillectomy using the T-14 questionnaire. The benefits of tonsillectomy on long-term quality of life further confirms its value within the paediatric population.

Effect of local cold application on glycogen recovery.

The purpose of this study was to investigate the effect of local cold application on muscle glycogen re-synthesis after exercise. Recreationally active male subjects (n=11) completed a 90-minute glycogen depleting ride, followed by 4 h of recovery. During recovery, ice was applied intermittently to one leg (IL) while the subjects other leg (CL) acted as a control. Intramuscular and rectal temperature was recorded continuously. A carbohydrate (1.8 g∙kg-1 bodyweight) beverage was supplied at 0 and 2 h post exercise. Muscle biopsies were taken immediately after exercise from the vastus lateralis and at 4 h post exercise for the analysis of muscle glycogen and muscle lactate. Leg circumference was measured 30, 60, 120, 180, and 240 minutes into recovery. The IL was colder than the CL from 15 minutes after initial ice application until the end recovery (P<0.05). Immediate post-exercise glycogen was similar between legs (55.3±7.4 vs. 56.1±7 mmol∙kg-1 wet weight for the iced vs. control, respectively). However, muscle glycogen was lower in the IL compared to the CL at 4 h post exercise (72±8.4 vs. 95±8.4 mmol∙kg-1 wet weight, respectively; P<0.05). Muscle lactate was lower in the IL after 4 h of recovery compared to the CL (1.6±.2 vs. 2.6±.2 mmol∙L-1, respectively; P<0.05). There was no difference in circumference between IL and CL. These data demonstrate a reduction in muscle glycogen re-synthesis with local cold application.

Human mRNA response to exercise and temperature.

The purpose of this research was to determine the mRNA response to exercise in different environmental temperatures. 9 recreationally active males (27±1 years, 77.4±2.7 kg, 13.5±1.5% fat, 4.49±0.15 L · min (-1) VO2 max) completed 3 trials consisting of 1 h cycling exercise at 60% Wmax followed by a 3 h recovery in the cold (7°C), room temperature (20°C), and hot (33°C) environments. Muscle biopsies were obtained pre, post, and 3 h post exercise for the analysis of glycogen and mRNA. Expired gases were collected to calculate substrate use. PGC-1α increased to a greater degree in the cold trial than in the room temperature trial (p=0.036) and the hot trial (p=0.006). PGC1-α mRNA was also higher after the room temperature trial than the hot trial (p=0.050). UCP3 and MFN2 mRNA increased with exercise (p<0.05), but were unaffected by temperature. COX was unaffected by exercise or temperature. Muscle glycogen decreased with exercise (p<0.05), but was no different among trials. Whole body VO2 was lower during exercise in the cold than exercise in the heat. However, VO2 was higher during recovery in the cold trial than in the room temperature and hot trials (p<0.05). This study presents evidence of PGC-1α temperature sensitivity in human skeletal muscle.

Vitamin A intoxication from reef fish liver consumption in Bermuda.

We report three historical cases of severe vitamin A intoxication in anglers who had consumed reef fish liver caught in Bermuda. The subsequent analyses of 35 fish livers from seven different fish species revealed that very high concentrations of vitamin A exist in tropical fish liver, even in noncarnivorous fish species. Large variations in concentrations were observed between specimens and between species. The angling population and (especially) pregnant women should be advised of this potential health threat.

Preliminary report on a catalyst derived from induced cells of Rhodococcus rhodochrous strain DAP 96253 that delays the ripening of selected climacteric fruit: bananas, avocados, and peaches.

Despite the use of refrigeration, improved packaging, adsorbents, and ethylene receptor blockers, on average, nearly 40% of all fruits and vegetables harvested in the US are not consumed. Many plant products, especially fruit, continue to ripen after harvesting, and as they do so, become increasingly susceptible to mechanical injury, resulting in increased rot. Other plant products during transportation and storage are susceptible to chill injury (CI). There is a real need for products that can delay ripening or mitigate the effects of CI, yet still permit full ripeness and quality to be achieved. Preliminary results are discussed where catalyst derived from cells of Rhodococcus rhodochrous DAP 96253, grown under conditions that induced high levels of nitrile hydratase, were able to extend the ripening and thus the shelf-life of selected climacteric fruits (banana, avocado, and peach). A catalyst, when placed in proximity to, but not touching, the test fruit delayed the ripening but did not alter the final ripeness of the fruit tested. Organoleptic evaluations conducted with control peaches and with peaches exposed to, but not in contact with, the catalyst showed that the catalyst-treated peaches achieved full, natural levels of ripeness with respect to aroma, flavor, sweetness, and juice content. Furthermore, the results of delayed ripening were achieved at ambient temperatures (without the need for refrigeration).

A public health approach to the impact of climate change on health in southern Africa - identifying priority modifiable risks.

Anthropogenic climate change and anticipated adverse impacts on human health as outlined by the Intergovernmental Panel on Climate Change (IPCC) are taken as given. A conceptual model for thinking about the spectrum of climate-related health risks ranging from distal and infrastructural to proximal and behavioural and their relation to the burden of disease pattern typical of sub-Saharan Africa is provided. The model provides a tool for identifying modifiable risk factors with a view to future research, specifically into the performance of interventions to reduce the impact of climate change.

Responding to climate change in southern Africa - the role of research.

Projections show that the effects of climate change in Africa will not be uniform over the region. The region is extremely vulnerable to the impact of climate change because of poverty, a high pre-existing disease burden, fragmented health services and existing water and food insecurity. Despite the consensus that locally relevant information is necessary to inform policy and practice related to climate change, very few studies assessing the association between climate change and health in southern Africa have been conducted. More complete information is therefore urgently needed for the southern African region to estimate the health risks from projected future changes in climate.

Knowledge and utilization of palliative radiotherapy by pediatric oncologists.

BACKGROUND AND PURPOSE: Palliative radiotherapy (PRT) is a routine part of oncology care in adult patients, but it is used much less frequently among children with incurable cancer. We surveyed Canadian pediatric oncologists to learn about their knowledge and use of PRT and to identify potential barriers to referral. METHODS: A 13-item questionnaire assessing PRT knowledge and utilization was sent to 80 Canadian pediatric oncologists. RESULTS: The survey completion rate was 80%, with most respondents being providers of palliative care for children and making referrals for PRT. Although 62% had received training in radiation oncology, only 28% had received formal palliative care training. Respondents with palliative care training were found to be significantly more knowledgeable about PRT and were more likely to refer children for PRT (p < 0.01). Only 59% of respondents thought that they had adequate knowledge about the indications for PRT. A positive correlation was found between knowledge about the indications for PRT and referral for treatment (p < 0.01). Among survey respondents, 51% believed that PRT was underutilized, and the perceived barriers to PRT referral included patient or family reluctance, distance to the cancer centre, belief that PRT has little impact on quality of life, and concerns about toxicity. CONCLUSIONS: Palliative radiotherapy is considered to be underutilized among children. This situation appears to be related, in part, to inadequate knowledge and training among pediatric oncologists, suggesting that more emphasis needs to be placed on pediatric palliative care education.

Meningoencephalitis in a polar bear caused by equine herpesvirus 9 (EHV-9).

A 12-year-old female polar bear (Ursus maritimus) developed a sudden onset of muscle tremors, erratic circling, increased blinking, head shaking, and ptyalism, which progressed to partial and generalized seizures. Ancillary diagnostic tests were inconclusive, and the only significant laboratory finding was nonsuppurative pleocytosis of cerebrospinal fluid. Euthanasia was elected. Microscopic evaluation demonstrated multifocal, random nonsuppurative meningoencephalitis involving most prominently the rostral cerebral cortex, as well as the thalamus, midbrain, and rostral medulla. Lesions consisted of inflammation, neuronal necrosis, gliosis, and both neuronal and glial basophilic intranuclear inclusion bodies. Immunohistochemistry with a polyclonal antibody reactive to several equine herpesviruses was positive within affected areas of the brain, and polymerase chain reaction conclusively demonstrated the presence of only equine herpesvirus 9. The clinical and morphologic features of this case resemble other fatal herpesvirus encephalitides derived from interspecies transmission and underscore the need for extreme caution when managing wild or captive equids.

Amygdala projections to central amygdaloid nucleus subdivisions and transition zones in the primate.

In rats and primates, the central nucleus of the amygdala (CeN) is most known for its role in responses to fear stimuli. Recent evidence also shows that the CeN is required for directing attention and behaviors when the salience of competing stimuli is in flux. To examine how information flows through this key output region of the primate amygdala, we first placed small injections of retrograde tracers into the subdivisions of the central nucleus in Old world primates, and examined inputs from specific amygdaloid nuclei. The amygdalostriatal area and interstitial nucleus of the posterior limb of the anterior commissure (IPAC) were distinguished from the CeN using histochemical markers, and projections to these regions were also described. As expected, the basal nucleus and accessory basal nucleus are the main afferent connections of the central nucleus and transition zones. The medial subdivision of the central nucleus (CeM) receives a significantly stronger input from all regions compared to the lateral core subdivision (CeLcn). The corticoamygdaloid transition zone (a zone of confluence of the medial parvicellular basal nucleus, paralaminar nucleus, and the sulcal periamygdaloid cortex) provides the main input to the CeLcn. The IPAC and amygdalostriatal area can be divided in medial and lateral subregions, and receive input from the basal and accessory basal nucleus, with differential inputs according to subdivision. The piriform cortex and lateral nucleus, two important sensory interfaces, send projections to the transition zones. In sum, the CeM receives broad inputs from the entire amygdala, whereas the CeLcn receives more restricted inputs from the relatively undifferentiated corticoamygdaloid transition region. Like the CeN, the transition zones receive most of their input from the basal nucleus and accessory basal nucleus, however, inputs from the piriform cortex and lateral nucleus, and a lack of input from the parvicellular accessory basal nucleus, are distinguishing afferent features.

Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1).

BACKGROUND: Patients with neurofibromatosis 1 (NF1) are shorter than expected and often have low bone mineral density (BMD), but the pathogenesis of these bony problems is poorly understood. METHODS: We performed an exploratory study of BMD, 18 laboratory measures of bone metabolism, and fracture history in 72 adult NF1 patients. RESULTS: Eight of the 18 clinical biochemical measures of bone health had at least 10% of NF1 patients outside the standard reference range. Serum 25-hydroxy-vitamin D concentrations were low in 56% of the NF1 patients, serum parathyroid hormone (PTH) concentrations were high in 34%, and urine deoxypyridinoline cross-link concentrations were high in 50%. Mean serum 25-hydroxy-vitamin D concentrations were significantly lower in people with NF1 than in season matched controls in both summer (p = 0.008) and winter (p<0.001). 36 (50%) of the 72 people with NF1 studied had BMD consistent with osteopenia, and 14 (19%) had BMD consistent with osteoporosis. High serum PTH concentration, high serum bone tartrate resistant acid phosphatase concentration, and high serum calcium concentration were associated with lower BMD among the NF1 patients. Males were more likely than females to have low BMD. The reported frequency of fractures in individuals with NF1 was much higher than in their unaffected siblings and spouses (p<0.001), and pathological fractures were reported only in NF1 patients. CONCLUSION: People with NF1 often have a generalised abnormality of bone metabolism. Further studies are needed to determine the biochemical and molecular basis of this abnormality.

Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas.

BACKGROUND: Plexiform neurofibromas are benign tumours that occur in more than half of people with neurofibromatosis 1 (NF1). These tumours can cause serious complications and can also progress to malignant peripheral nerve sheath tumours (MPNSTs), one of the leading causes of death among NF1 patients. Plexiform neurofibromas are clinically heterogeneous, and knowledge of their natural history is limited. In order to characterise the growth of plexiform neurofibromas better, we performed serial magnetic resonance imaging (MRI) in NF1 patients with such tumours. METHODS: MRI was done on 44 plexiform neurofibromas in 34 NF1 patients (median age 10 years; range 1-47 years). Each tumour was measured in two dimensions from the MRI scan, and the area and growth rate were calculated. The median length of follow-up was 6 years, with an average interval of 3 years between scans. RESULTS: 36 tumours remained stable in size throughout the period of follow-up. 8 tumours increased in size; all occurred in patients who were under 21 years of age when first studied. The single exception was a man who developed rapid tumour growth and pain in a plexiform neurofibroma that had been followed for 10 years. Biopsy showed the presence of an MPNST. CONCLUSION: Longitudinal MRI is a valuable means of monitoring the growth of plexiform neurofibromas in individuals with NF1.

A report on location of death in paediatric palliative care between home, hospice and hospital.

This retrospective study analysed data for 703 children who died from 2000 to 2006 to examine where children with a broad range of progressive, life-limiting illnesses actually die when families are able to access hospital, paediatric hospice facility and care at home. There was an overall even distribution for location of death in which 35.1% of children died at home, 32.1% died in a paediatric hospice facility, 31.9% in hospital and 0.9% at another location. Previous research suggests a preference for home as the location of death, but these studies have primarily focused on adults, children with cancer or settings without paediatric hospice facilities available as an option. Our results suggest that the choice of families for end-of-life care is equally divided amongst all three options. Given the increasing numbers of children's hospices worldwide, these findings are important for clinicians, care managers and researchers who plan, provide and evaluate the care of children with life-limiting illness.

Balancing the risks and the benefits of local fish consumption in Bermuda.

Fish consumption today is widely recognized as highly beneficial since it constitutes a good source of several essential nutrients, such as selenium and polyunsaturated fatty acids (n-3 PUFA). However, fish can also contain contaminants such as mercury, which make the consumer, especially pregnant women, confused about the risk-benefit balance associated with fish consumption. This is particularly true for tropical fish species for which little information is available. We have previously reported that some Bermudian neonates had elevated mercury in their umbilical blood compared with international guidelines. The objective of this study was to give precise and balanced information on the content of mercury, selenium and PUFA in the most consumed fish species in Bermuda. In 2003 and 2006, a total of 307 fish were collected from 43 fish species and 351 samples were analysed (305 flesh samples, 44 liver samples, one roe and one fat sample) by inductively coupled plasma-mass spectrometry (ICP-MS) (metals) and high-resolution gas chromatography (HRGC) (fatty acids). Results show that mercury varies among species from 0.03 to 3.3 microg g(-1) and that it is possible for at-risk groups such as pregnant women to make informed choices concerning fish consumption, e.g. maximizing fish species rich in nutrients and low in mercury.