Sensorless volumetric reconstruction of fetal brain freehand ultrasound scans with deep implicit representation.

Three-dimensional (3D) ultrasound imaging has contributed to our understanding of fetal developmental processes by providing rich contextual information of the inherently 3D anatomies. However, its use is limited in clinical settings, due to the high purchasing costs and limited diagnostic practicality. Freehand 2D ultrasound imaging, in contrast, is routinely used in standard obstetric exams, but inherently lacks a 3D representation of the anatomies, which limits its potential for more advanced assessment. Such full representations are challenging to recover even with external tracking devices due to internal fetal movement which is independent from the operator-led trajectory of the probe. Capitalizing on the flexibility offered by freehand 2D ultrasound acquisition, we propose ImplicitVol to reconstruct 3D volumes from non-sensor-tracked 2D ultrasound sweeps. Conventionally, reconstructions are performed on a discrete voxel grid. We, however, employ a deep neural network to represent, for the first time, the reconstructed volume as an implicit function. Specifically, ImplicitVol takes a set of 2D images as input, predicts their locations in 3D space, jointly refines the inferred locations, and learns a full volumetric reconstruction. When testing natively-acquired and volume-sampled 2D ultrasound video sequences collected from different manufacturers, the 3D volumes reconstructed by ImplicitVol show significantly better visual and semantic quality than the existing interpolation-based reconstruction approaches. The inherent continuity of implicit representation also enables ImplicitVol to reconstruct the volume to arbitrarily high resolutions. As formulated, ImplicitVol has the potential to integrate seamlessly into the clinical workflow, while providing richer information for diagnosis and evaluation of the developing brain.

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Respirable crystalline silica dust exposure and regulated occupational respiratory diseases in the Zambian copper mining sector: a review and recommendations

Background: Exposure to respirable dust is widespread in the mining industry. One of the significant components in dust is respirable crystalline silica (RCS), which causes pulmonary silicosis; RCS exposure is also associated with tuberculosis. The health effects of exposure to RCS in Zambian copper miners are unclear. Objectives: This review describes RCS exposure, associated occupational respiratory diseases, and existing dust exposure management programmes in the Zambian copper mining industry. Research gaps are also identified. Methods: Online search engines (Google Scholar, PubMed, and Web of Science) were used to identify relevant published literature, and governmental databases and websites were searched for information. Results: Only two studies have reported RCS dust exposure in the Zambian copper mining industry, and seven studies describe related diseases. The Zambian Ministry of Health reports on only two occupational respiratory diseases: silicosis and tuberculosis (TB). Zambia does not have an occupational health policy or programmes that protect workers in dusty operations from exposure to RCS. Conclusion: Little is known about exposure to RCS and related occupational diseases in the Zambian copper mining industry. The absence of legislative guidelines for an RCS monitoring programme places copper miners at risk of developing respiratory diseases because of high and uncontrolled RCS levels. An RCS management programme should be developed and implemented to investigate the exposure of miners to RCS, and to promote the implementation of control measures

Subcortical segmentation of the fetal brain in 3D ultrasound using deep learning.

The quantification of subcortical volume development from 3D fetal ultrasound can provide important diagnostic information during pregnancy monitoring. However, manual segmentation of subcortical structures in ultrasound volumes is time-consuming and challenging due to low soft tissue contrast, speckle and shadowing artifacts. For this reason, we developed a convolutional neural network (CNN) for the automated segmentation of the choroid plexus (CP), lateral posterior ventricle horns (LPVH), cavum septum pellucidum et vergae (CSPV), and cerebellum (CB) from 3D ultrasound. As ground-truth labels are scarce and expensive to obtain, we applied few-shot learning, in which only a small number of manual annotations (n = 9) are used to train a CNN. We compared training a CNN with only a few individually annotated volumes versus many weakly labelled volumes obtained from atlas-based segmentations. This showed that segmentation performance close to intra-observer variability can be obtained with only a handful of manual annotations. Finally, the trained models were applied to a large number (n = 278) of ultrasound image volumes of a diverse, healthy population, obtaining novel US-specific growth curves of the respective structures during the second trimester of gestation.

Intensity Augmentation to Improve Generalizability of Breast Segmentation Across Different MRI Scan Protocols.

OBJECTIVE: The segmentation of the breast from the chest wall is an important first step in the analysis of breast magnetic resonance images. 3D U-Nets have been shown to obtain high segmentation accuracy and appear to generalize well when trained on one scanner type and tested on another scanner, provided that a very similar MR protocol is used. There has, however, been little work addressing the problem of domain adaptation when image intensities or patient orientation differ markedly between the training set and an unseen test set. In this work we aim to address this domain shift problem. METHOD: We propose to apply extensive intensity augmentation in addition to geometric augmentation during training. We explored both style transfer and a novel intensity remapping approach as intensity augmentation strategies. For our experiments, we trained a 3D U-Net on T1-weighted scans. We tested our network on T2-weighted scans from the same dataset as well as on an additional independent test set acquired with a T1-weighted TWIST sequence and a different coil configuration. RESULTS: By applying intensity augmentation we increased segmentation performance for the T2-weighted scans from a Dice of 0.71 to 0.88. This performance is very close to the baseline performance of training with T2-weighted scans (0.92). On the T1-weighted dataset we obtained a performance increase from 0.77 to 0.85. CONCLUSION: Our results show that the proposed intensity augmentation increases segmentation performance across different datasets. SIGNIFICANCE: The proposed method can improve whole breast segmentation of clinical MR scans acquired with different protocols.

Nitrogen deposition changes ectomycorrhizal communities in Swiss beech forests.

Atmospheric pollution has implications for the health and diversity of temperate forests covering large parts of central Europe. Long-term elevated anthropogenic deposition of nitrogen (N) is driving forest ecosystems from the limitation by N to other nutrients and is found to affect tree health and ectomycorrhizal fungi (EMF), which most trees depend on for nutrient uptake. However, the consequence of EMF community changes for trees remains unclear. Therefore, we investigated changes in EMF communities on root tips and in soil of beech forests along a N deposition gradient ranging between 16 and 33kgNha-1a-1, where high N deposition was found to negatively affect tree growth and nutrient levels. The most important factors significantly explaining variation in root tip and mycelium EMF community composition in both root tips and mesh bags were increased N deposition, base saturation, growing season temperature and precipitation. With increasing N deposition, fine root length, EMF root colonization, EMF diversity on root tips and in soil, and production of extramatrical mycelium decreased significantly. Foliar P and potassium (K) were positively associated with increasing EMF diversity and we found EMF community composition to be associated with foliar P and N:P ratio. The decrease in root colonization, mesh bag ingrowth and abundance of the important species Cenococcum geophilum as well as high biomass species with increasing N availability clearly indicate repercussions for belowground carbon allocation, although some indicator species for high N deposition and low foliar P have long mycelia and may reflect a potential optimization of host P uptake. Our study supports the hypothesis that the decrease in nutrient uptake in beech forests across Europe is related to changes in EMF communities and suggests that continued high N deposition changes soil carbon and nutrient cycles, thereby affecting forest ecosystem health.

Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.

Growth restriction in the rat alters expression of cardiac JAK/STAT genes in a sex-specific manner.

Uteroplacental insufficiency resulting in intrauterine growth restriction has been associated with the development of cardiovascular disease, coronary heart disease and increased blood pressure, particularly in males. The molecular mechanisms that result in the programming of these phenotypes are not clear. This study investigated the expression of cardiac JAK/STAT signalling genes in growth restricted offspring born small due to uteroplacental insufficiency. Bilateral uterine vessel ligation was performed on day 18 of pregnancy to induce growth restriction (Restricted) or sham surgery (Control). Cardiac tissue at embryonic day (E) 20, postnatal day (PN) 1, PN7 and PN35 in male and female Wistar (WKY) rats (n=7-10 per group per age) was isolated and mRNA extracted. In the heart, there was an effect of age for males for all genes examined there was a decrease in expression after PN1. With females, JAK2 expression was significantly reduced after E20, while PI3K in females was increased at E30 and PN35. Further, mRNA expression was significantly altered in JAK/STAT signalling targets in Restricteds in a sex-specific manner. Compared with Controls, in males, JAK2 and STAT3 were significantly reduced in the Restricted, while in females SOCS3 was significantly increased and PI3K significantly decreased in the Restricted offspring. Finally, there were specific differences in the levels of gene expression within the JAK/STAT pathway when comparing males to females. Thus, growth restriction alters specific targets in the JAK/STAT signalling pathway, with altered JAK2 and STAT3 potentially contributing to the increased risk of cardiovascular disease in the growth restricted males.

Developing a clinical model to predict the need for relaparotomy in severe intra-abdominal sepsis secondary to complicated appendicitis.

BACKGROUND: Complex intra-abdominal sepsis secondary to acute appendicitis is common in South Africa, and management frequently involves relaparotomy. The decision to perform relaparotomy is often difficult, and this study aimed to develop a clinical model to aid the decision-making process. METHOD: The study was conducted from January 2008 to December 2012 at Edendale Hospital, Pietermaritzburg. All patients with intraoperatively confirmed acute appendicitis and all patients in this group who subsequently underwent relaparotomy were included. The clinical course, intraoperative findings and outcome of all patients were recorded until discharge (or death). Using a combination of preoperative and intraoperative parameters, a clinical model was developed to predict the need for relaparotomy. RESULTS: Of the total of 1 000 patients identified, 54.1% were males. The median age for all patients was 21 years. Of 406 relaparotomies, 227 (55.9%) were planned and 179 (44.1%) on demand (expectant treatment). In the relaparotomy group, 367 patients (90.4%) had positive findings. Logistic regression analysis showed that the following four factors accurately predicted the need for subsequent relaparotomy: patients referred from any rural centre, duration of illness >5 days, heart rate >120 bpm, and perforation associated with generalised intraabdominal sepsis. Th is model had a predictive value of >90%. CONCLUSION: We have constructed a model that uses clinical data available at initial laparotomy to predict the need for subsequent relaparotomy in patients with complicated acute appendicitis. It is hoped that this model can be integrated into routine clinical practice, but further study is first needed to validate this model.

Quantifying the disparity in outcome between urban and rural patients with acute appendicitis in South Africa.

BACKGROUND: Acute appendicitis in South Africa is associated with higher morbidity than in the developed world. Objective. To compare outcomes of urban and rural patients in KwaZulu-Natal and to determine whether there are disparities in outcome. METHODS: We conducted a prospective study from September 2010 to September 2012 at Edendale Hospital in Pietermaritzburg, South Africa. All patients who presented with acute appendicitis were included. The operative and clinical course of urban and rural patients was compared. Results. A total of 500 patients were included, with 200 patients in the rural group and 300 in the urban group. Those from the rural group had a significantly longer duration of symptoms prior to presentation. All septic parameters were significantly worse in the rural group. Significantly more patients from the rural group required a laparotomy (77% v. 51% urban; p<0.001). Inflamed, non-perforated appendicitis was more commonly seen in the urban group (52.3% v. 21% rural; p<0.001), while perforated appendicitis was much more common in the rural group (79% v. 47.7% urban; p<0.001). Perforation associated with generalised, four-quadrant intra-abdominal contamination was significantly higher in the rural group than the urban group (60.5% v. 21%, respectively; p<0.05). Significantly more patients from the rural group required an open abdomen (46% v. 12% urban; p<0.001) and ≥1 re-laparotomies to control severe intra-abdominal sepsis (60.5% v. 23.3% urban; p<0.001). CONCLUSION: We have identified rural origin as an independent indicator of poor outcome. Possible reasons may include difficulty in accessing the health system or delay in transfer to a regional hospital. These need to be investigated further.

Maternal and fetal outcomes of HIV-infected and non-infected pregnant women admitted to two intensive care units in Pietermaritzburg, South Africa.

BACKGROUND: Outcomes of HIV-positive pregnant patients admitted to intensive care units (ICUs) are controversial. OBJECTIVE: To determine maternal and fetal outcomes of HIV-positive patients admitted to ICUs. METHODS: Pregnant patients admitted to ICUs were enrolled in the study. On admission, they were classified as having low (<50%) or high (≥50%) risk of death by GRAMPT stratification score. The primary maternal outcome was death or hypoxic-ischaemic brain injury (HIBI), while fetal outcomes recorded were Apgar score, birth weight, and delivery of the fetus to facilitate maternal care. RESULTS: There were 84 admissions to the ICUs: 66 (78.6%) were post-partum and 18 (21.4%) antepartum. The HIV sero-status was as follows: 11 (13.1%) HIV status unknown; 42 (50%) HIV-negative and 31 (36.9%) HIV-positive. The most common pre-ICU admission diagnoses were pneumonia (19.4%) in HIV-positive patients and eclampsia (31%) in HIV-negative patients. Maternal outcomes showed a worsening trend among the HIV-positive women when compared with those who were HIV-negative (high GRAMPT, 1.91 relative risk of death/HIBI in HIV-positive; 95% CI 0.57 - 6.44). Forty-two patients gave birth within 24 hours prior to ICU admission; 3 gave birth while in ICU and none gave birth within 24 hours following ICU discharge. Outcomes of the 45 infants born to HIV-positive women were worse than for those born to HIV-negative patients (except for Apgar scores 1 - 6). Performance of the GRAMPT model for prediction of maternal mortality/HIBI was best in hypertensive patients (ROC: AUC 0.72; 95% CI 0.48 - 0.96). CONCLUSION: With the exception of Apgar scores 1 - 6, all outcomes showed worsening trends among infants born to HIV-positive mothers. Large multicentre studies are needed to confirm our findings.

Trauma unit workload at King Edward VIII Hospital, Durban, KwaZulu-Natal.

Each year, 70 000 South Africans are killed by trauma and a further 3.5 million seek trauma care. We analysed 1 465 trauma patients at the regional-level King Edward VIII hospital (KE8H) in eThekwini Municipality. Mean patient age was 29 years. Peaks in patient numbers were observed mid-month, at month-end, between 08h00 and 12h00 daily and on Saturday and Sunday nights. Most injuries occurred on roads, at informal settlements and at bars/shebeens. More than 44% of injuries had a violent cause. The pattern of presentation was more in line with a primary healthcare setting than a referral centre. Reliable and accurate injury trend information is required for effective strategies to curb South Africa's high injury mortality and morbidity rates. Epidemiological databases are needed, as well as safe, robust and ethical systems for collecting, collating, analysing and disseminating non-fatal injury-related data.

Real-time computation of subdiffraction-resolution fluorescence images.

In the recent past, single-molecule based localization or photoswitching microscopy methods such as stochastic optical reconstruction microscopy (STORM) or photoactivated localization microscopy (PALM) have been successfully implemented for subdiffraction-resolution fluorescence imaging. However, the computational effort needed to localize numerous fluorophores is tremendous, causing long data processing times and thereby limiting the applicability of the technique. Here we present a new computational scheme for data processing consisting of noise reduction, detection of likely fluorophore positions, high-precision fluorophore localization and subsequent visualization of found fluorophore positions in a super-resolution image. We present and benchmark different algorithms for noise reduction and demonstrate the use of non-maximum suppression to quickly find likely fluorophore positions in high depth and very noisy images. The algorithm is evaluated and compared in terms of speed, accuracy and robustness by means of simulated data. On real biological samples, we find that real-time data processing is possible and that super-resolution imaging with organic fluorophores of cellular structures with approximately 20 nm optical resolution can be completed in less than 10 s.

A phylogenetic study of Boletus section Boletus in Europe.

A phylogenetic study of the species in Boletus sect. Boletus was undertaken using the molecular markers ITS1-5.8S-ITS2 and GAPDH. Four well-supported lineages, one comprising Boletus edulis s.l., the others referring to B. aereus, B. reticulatus and B. pinophilus have been distinguished. The ML and MP trees of ITS showed remarkably low resolution within the B. edulis clade, and confirmed earlier published results, despite the use of samples from a wider geographical area and different hosts. The results of GAPDH demonstrate clearly that this low resolution must be ascribed to a low genetic variability with the B. edulis clade, and make clear that morphological and ecological characters have been overestimated within this species complex. Boletus edulis is therefore defined as a variable species with a wide morphological, ecological and geographic range, and includes several specific and subspecific taxa described in the literature (e.g. B. betulicola, B. persoonii, B. quercicola and B. venturii). Three other European species (B. aereus, B. pinophilus and B. reticulatus) are well delimited species based on morphology and our genetic data.

In-target production of high specific radioactivity [15O]nitrous oxide by deuteron irradiation of nitrogen gas.

A simple and rapid production method for high specific radioactivity [15O]N2O has been developed based on the 14N(d,n)15O reaction on high-purity nitrogen gas in a flow-through target irradiated with a 0.5 microA beam of 7 MeV deuterons. The [15O]N2O formed during irradiation is selectively concentrated from the target effluent by adsorption on a zeolite during 150 s and subsequently released by rapid heating into a pulse with a full width at half maximum of 3.5 s. The radioactivity and specific radioactivity in the pulse amount to 4 MBq [15O]N2O and 4.5 x 10(13) Bq/mol respectively with a radiochemical purity >99.95%. A tenfold higher specific radioactivity may be feasible at larger beam currents. It was shown that stable N2O was also formed during irradiation. Based on responses to variations in various parameters during irradiation and on analyses performed on the products, an explanation is given on the mechanisms of in-target [15O]N2O and N2O formation, involving reaction of a particular excited state of O3 with N2.

Spectrophotometric and direct-reading methods for the analysis of gas phase peroxyacetic acid.

A new method for the determination of peroxyacetic acid (PAA) in gas phase samples is described. It is based on the oxidation of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate) by PAA with formation of a radical cation which is characterized by four strong absorption maxima between 405 nm and 810 nm. These allow for sensitive spectrophotometric determination of the peracid. The selectivity of the method towards hydrogen peroxide is strongly dependent on the sampling method used. Impinger sampling and sampling based on the use of coated solid sorbents (test tubes) was performed. Limits of detection are 10(-8) mol, limits of quantification are 5 x 10(-8) mol, the linear range consists of 1.5 concentration decades in both cases. Using ABTS-coated test tubes above 1 x 10(-7) mol, direct reading of the results is possible and may be used as rapid screening method for the PAA concentration.

Determination of gas phase peroxyacetic acid using pre-column derivatization with organic sulfide reagents and liquid chromatography.

The first selective HPLC methods for the determination of peroxyacetic acid (PAA) in gas phase samples have been developed. PAA reacts with 2-([3-{2-[4-amino-2-(methylsulfanyl)phenyl]- 1-diazenyl}phenyl]sulfonyl)-1-ethanol (ADS) to form the corresponding sulfoxide. Sampling may be performed in impingers using aqueous solutions of the reagent or by test tubes with the reagent coated on a solid sorbent. Sulfide and sulfoxide are separated by means of HPLC and detected at a wavelength of 410 nm. The method is highly selective for PAA in the presence of hydrogen peroxide when sampling in impingers. A 10,000-fold excess of hydrogen peroxide leads to the same peak area compared to PAA. Limit of detection is 10(-8) mol PAA, thus corresponding to PAA concentration of 46 ppb when using a sampling time of 10 min with a flow-rate at 500 ml/min. Another sulfide reagent, methyl-p-tolyl sulfide (MTS) has been used in a similar way with impinger sampling. Major advantages of ADS towards MTS are improved UV-Vis spectroscopic properties and reduced volatility.

Characterization of a novel murine leukemia virus-related subgroup within mammals.

The murine leukemia virus (MuLV)-related retroviruses are one of seven genera which together constitute the family Retroviridae. They are widespread as both endogenous and exogenous agents within vertebrates and have been associated with a variety of malignancies and other disorders. We isolated and characterized 12 endogenous representatives of this genus from a number of mammalian hosts. Subsequent sequence analysis revealed that the isolated viruses cluster into two clearly distinct groups. All of the exogenous MuLV-related retroviruses which have been isolated to date, as well as several endogenous examples, fall into the first group, whereas the second group is represented solely by endogenous representatives, including human endogenous retrovirus type E (HERV.E). The two groups are widespread within mammals, with both often present within one animal species. Despite this, there is no evidence to date that recombination between members of the different groups has occurred. Genetic distances and several other properties of the HERV.E genome suggest that if exogenous members of this subgroup exist, they are likely to have biological properties different from those of the other exogenous viruses of this genus. Several of these viruses are known to have been integrated within their hosts' genomes for a long period of time, and a most recent divergence date for the MuLV and HERV.E subgroups can thus be proposed. This date, approximately 30 million years ago, is the most recent date possible, and it is probable that the actual period of time since their divergence is significantly longer.

3-Nitropyrrole and 5-nitroindole as universal bases in primers for DNA sequencing and PCR.

3-Nitropyrrole and 5-nitroindole have been assessed as universal bases in primers for dideoxy DNA sequencing and in the polymerase chain reaction (PCR). In contrast to a previous report, we have found that the introduction of more than one 3-nitropyrrole residue at dispersed positions into primers significantly reduced their efficiency in PCR and sequencing reactions. Primers containing 5-nitroindole at multiple dispersed positions were similarly affected; for both bases only a small number of substitutions were tolerated. In PCR experiments neither base, when incorporated into primers in codon third positions, was as effective as hypoxanthine, which was incorporated in six codon third positions in a 20mer oligomer. However, primers containing up to four consecutive 5-nitroindole substitutions performed well in both PCR and sequencing reactions. Consecutive 3-nitropyrrole substitutions were tolerated, but less well in comparable reactions.

Characterization of the three 125I-iodination isomers of human insulin-like growth factor I (IGF1).

Human insulin-like growth factor I (IGF1) was labeled with 125I and the resulting mixture of iodination isomers was separated by reverse-phase HPLC. Three major radioactive peaks were isolated and identified by sequencing as the expected three monoiodinated species. The ranking of the affinities of the three isomers for the human IGF1 receptor was found to be Tyr24(125I) > Tyr31(125I) >> Tyr60(125I). The Tyr31(125I) isomer was shown to have an affinity similar to that of unlabeled IGF1 and is thus the tracer of choice for IGF1. The tracers were stable upon storage at -20 degrees C for at least 3 months.