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Abstract Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have demonstrated the safe and efficacious use of fibrinogen replacement therapy (FRT) as a therapeutic approach to prevent hemorrhage and fetal loss in pregnant women with CD. In this case report, we present a 28‐year‐old pregnant woman who sought testing for CD given her family history. She denied any current or previous bleeding symptoms. Laboratory testing confirmed the diagnosis of CD. She was treated with FRT and prophylactic anticoagulation starting in her third trimester. She had preterm labor that prompted an urgent cesarean section with FRT support. This case adds to the sparse literature about fibrinogen disorders in pregnancy, and highlights the benefits, safety, and tolerability of FRT and prophylactic anticoagulation in pregnant women with CD. Finally, it emphasizes the importance of a multidisciplinary team approach for an uneventful delivery.

One of the advantages of using Islamic social funds is the increased ability of microfinance institutions to provide financial services to the poor. This study aims to (1) investigates the characteristics of the clients of the Islamic Charity Based Microfinance (ICBM) program; (2) test whether the clients ICBM program are more vulnerable than the non clients group (3) discuss the rationale of why poor excluded from the zakat based microfinance program. The study was conducted in the microfinance program at zakat institutions namely Baitul Maal Muamalat (BMMI), BAZNAS, and Baitul Maal Beringharjo (BMB). A total of 236 respondents including clients and non-clients of three case study institutions were participated in this study. The data is analyzed using binomial logit model to evaluate factors affecting clients participation in ICBM programs in Indonesia. The findings show that clients and non-clients of ICBM have a similar demographic profile and the majority ICBM clients live above the national poverty line, yet they live perilously close to the edge of the poverty line. Using logistic regression, this study found that the higher the client’s income level, the higher the probability of their being selected in the program. This findings contradict with the existing Islamic microfinance literature that claim ICBM institutions in general could demonstrate a capacity to extend their services more widely to the poorest if Islamic charity is the main source of microfinance funding. This study suggests some possible barriers to include the poor in the microfinance including institutional selection policy and self exclusion factors.

Abstract Over the past decade, humanitarian events affected on average 120 million people annually. Whilst many of these events are human-induced, a large number of the 400 or so complex humanitarian emergencies that require international response each year are natural. Such events result in loss of life, injure and maim survivors, destroy infrastructure and give rise to psycho-social trauma. Aid agencies working alongside affected communities must address all these consequences as part of their responses. What is also required though is an appreciation that worldviews will inform how affected communities both understand the cause of the event, their role in the event and how they will subsequently participate in rebuilding or reconstruction programs. Disasters can be affected by religious beliefs. With more than 85% of the global population self-professing religious belief, these worldviews are often shaped in whole or in part by sacred texts, religious teachings and sectarian practices. In this regard, it is not uncommon for those affected by disasters (particularly natural disasters) to genuinely describe these events as ‘acts of God’. Effective responses require the local context to be central in assessing needs and determining capacities. This must include an understanding of and authentic engagement with religious beliefs and how this may affect how the humanitarian event interacts with these beliefs. There is though little evidence as to how professional humanitarian workers accommodate the religious beliefs of local populations in their planning, implementation and evaluation of humanitarian responses. This paper draws on the experiences of humanitarian workers based in the USA and Australia from both faith-based and secular international non-governmental organizations to consider both how these workers themselves accommodate the religious views of affected communities in their responses and also their experience as to how such views affect the effectiveness of responses. This paper will consider why aid agencies must incorporate (and appreciate) different worldviews around disasters in order to more effectively respond to the needs of communities affected by humanitarian events. It will also identify difficulties and opportunities experienced by individual humanitarian practitioners as well as agencies when working in such environments.

Objective: We report cases of central or atypical skull base osteomyelitis and review issues related to the diagnosis and treatment. Methods: The four cases presented, which were drawn from the Oxford, United Kingdom, skull base pathology database, had a diagnosis of central skull base osteomyelitis. Results: Four cases are presented in which central skull base osteomyelitis was diagnosed. Contrary to malignant otitis externa, our cases were not preceded by immediate external infections and had normal external ear examinations. They presented with headache and a variety of cranial neuropathies. Imaging demonstrated bone destruction, and subsequent microbiological analysis diagnosed infection and prompted prolonged antibiotic treatment. Conclusion: We concluded that in the diabetic or immunocompromised patient, a scenario of headache, cranial neuropathy, and bony destruction on imaging should raise the possibility of skull base osteomyelitis, even in the absence of an obvious infective source. The primary goal should still be to exclude an underlying malignant cause. [ABSTRACT FROM AUTHOR]

Hydrate problems in industry have historically motivated modeling of hydrates and hydrate phase transition dynamics, and much knowledge has been gained during the last fifty years of research. The interest in natural gas hydrate as energy source is increasing rapidly. Parallel to this, there is also a high focus on fluxes of methane from the oceans. A limited portion of the fluxes of methane comes directly from natural gas hydrates but a much larger portion of the fluxes involves hydrate mounds as a dynamic seal that slows down leakage fluxes. In this work we review some of the historical trends in kinetic modeling of hydrate formation and discussion. We also discuss a possible future development over to classical thermodynamics and residual thermodynamics as a platform for all phases, including water phases. This opens up for consistent thermodynamics in which Gibbs free energy for all phases are comparable in terms of stability, and also consistent calculation of enthalpies and entropies. Examples are used to demonstrate various stability limits and how various routes to hydrate formation lead to different hydrates. A reworked Classical Nucleation Theory (CNT) is utilized to illustrate that nucleation of hydrate is, as expected from physics, a nano-scale process in time and space. Induction times, or time for onset of massive growth, on the other hand, are frequently delayed by hydrate film transport barriers that slow down contact between gas and liquid water. It is actually demonstrated that the reworked CNT model is able to predict experimental induction times.

Summary: Background: In 2015, an estimated 303 000 women died in pregnancy and childbirth. Obstetric haemorrhage, sepsis, and hypertensive disorders of pregnancy account for more than 50% of maternal deaths worldwide. There are effective treatments for these pregnancy complications, but they require early detection by measurement of vital signs and timely administration to save lives. The primary aim of this trial was to determine whether implementation of the CRADLE Vital Sign Alert and an education package into community and facility maternity care in low-resource settings could reduce a composite of all-cause maternal mortality or major morbidity (eclampsia and hysterectomy). Methods: We did a pragmatic, stepped-wedge, cluster-randomised controlled trial in ten clusters across Africa, India, and Haiti, introducing the device into routine maternity care. Each cluster contained at least one secondary or tertiary hospital and their main referral facilities. Clusters crossed over from existing routine care to the CRADLE intervention in one of nine steps at 2-monthly intervals, with CRADLE devices replacing existing equipment at the randomly allocated timepoint. A computer-generated randomly allocated sequence determined the order in which the clusters received the intervention. Because of the nature of the intervention, this trial was not masked. Data were gathered monthly, with 20 time periods of 1 month. The primary composite outcome was at least one of eclampsia, emergency hysterectomy, and maternal death. This study is registered with the ISRCTN registry, number ISRCTN41244132. Findings: Between April 1, 2016, and Nov 30, 2017, among 536 223 deliveries, the primary outcome occurred in 4067 women, with 998 maternal deaths, 2692 eclampsia cases, and 681 hysterectomies. There was an 8% decrease in the primary outcome from 79·4 per 10 000 deliveries pre-intervention to 72·8 per 10 000 deliveries post-intervention (odds ratio [OR] 0·92, 95% CI 0·86–0·97; p=0·0056). After planned adjustments for variation in event rates between and within clusters over time, the unexpected degree of variability meant we were unable to judge the benefit or harms of the intervention (OR 1·22, 95% CI 0·73–2·06; p=0·45). Interpretation: There was an absolute 8% reduction in primary outcome during the trial, with no change in resources or staffing, but this reduction could not be directly attributed to the intervention due to variability. We encountered unanticipated methodological challenges with this trial design, which can provide valuable learning for future research and inform the trial design of future international stepped-wedge trials. Funding: Newton Fund Global Research Programme: UK Medical Research Council; Department of Biotechnology, Ministry of Science & Technology, Government of India; and UK Department of International Development.

Approximately half of the daily oil production from the Canadian oil sands comes from the application of steam assisted gravity drainage (SAGD). Due to the high steam requirements of SAGD, many studies have focused on solvent injection as a means of reducing the steam consumption. One of the multiple variations of the steam-solvent injection process consists on the intermittent co-injection of solvent with steam, also known as a cyclic expanding-solvent (ES)-SAGD process. The current study represents a first attempt to create an analytical model that can describe a cyclic ES-SAGD process. The proposed analytical model uses previous SAGD and ES-SAGD models to describe the steam plus solvent stages of the process. The results obtained from the analytical model were contrasted against numerical simulation results for cases in which the solvent was hexane, pentane, and butane, as well as for cases in which hexane is a solvent and the injection cycle length is variable. In all cases, it was seen that the cumulative oil production computed by the analytical model and the numerical model are in good agreement. Over the range of conditions that were tested the absolute relative difference in the cumulative oil production, after a period of 10 years, ranged from 8.6% to 9.4%, with a median value of 9%. However, compared to the numerical simulations, the analytical model did not fully match the oil rate and the steam chamber shape. This difference was attributed to the analytical model’s simplified description of heat and mass transfer during the process. Thus, it is recommended that further studies be conducted, and recommendations for further investigations are given.

To provide a useful community resource for orthogonal assessment of NGS analysis software, we present the ICR142 NGS validation series. The dataset includes high-quality exome sequence data from 142 samples together with Sanger sequence data at 704 sites; 416 sites with variants and 288 sites at which variants were called by an NGS analysis tool, but no variant is present in the corresponding Sanger sequence. The dataset includes 293 indel variants and 247 negative indel sites, and thus the ICR142 validation dataset is of particular utility in evaluating indel calling performance. The FASTQ files and Sanger sequence results can be accessed in the European Genome-phenome Archive under the accession number EGAS00001001332.

Euglycemic diabetic ketoacidosis is a post market warning in patients with type 1 diabetes and type 2 diabetes treated with SGLT-2 inhibitors. We report a case of a 39-year-old obese female with presumed type 2 diabetes for seven years who presented to the emergency department with three days of nausea, vomiting, and abdominal pain. Due to previous total non-adherence with a prescribed insulin regimen, she was recently started on canagliflozin and liraglutide. The diagnosis of euDKA was missed in the initial evaluation as the blood glucose level was only 167 mg/dL. Further work up showed severe metabolic acidosis with an anion gap of 25 and positive ketones in the urine. She was treated successfully with dextrose water 5%/half normal saline and an insulin drip. As part of the work up, she tested positive for glutamic acid decarboxylase autoantibodies.Given the increasing utilization of SGLT-2 inhibitors and the fact that patients can present with near-normal glycemia, the diagnosis can be missed. Vigilance with the use of SGLT-2 inhibitors is necessary to decrease morbidity and potentially mortality particularly in patients with long-standing type 2 diabetes associated with marked β-cell insufficiency, type 1 diabetes mellitus, or latent autoimmune diabetes of adult onset. Keywords: SGLT-2 inhibitors, Canagliflozin, Euglycemic DKA, Near normal glucose level, Glutamic Acid Decarboxylase autoantibodies, Latent Autoimmune Diabetes of Adult onset (LADA)

Naturally occurring gas hydrates are regarded as an important future source of energy and considerable efforts are currently being invested to develop methods for an economically viable recovery of this resource. The recovery of natural gas from gas hydrate deposits has been studied by a number of researchers. Depressurization of the reservoir is seen as a favorable method because of its relatively low energy requirements. While lowering the pressure in the production well seems to be a straight forward approach to destabilize methane hydrates, the intrinsic kinetics of CH4-hydrate decomposition and fluid flow lead to complex processes of mass and heat transfer within the deposit. In order to develop a better understanding of the processes and conditions governing the production of methane from methane hydrates it is necessary to study the sensitivity of gas production to the effects of factors such as pressure, temperature, thermal conductivity, permeability, porosity on methane recovery from naturally occurring gas hydrates. A simplified model is the base for an ensemble of reservoir simulations to study which parameters govern productivity and how these factors might interact.

The amount of oil that is contained in the Canadian oil sands represent the third largest oil accumulation in the world. Approximately half of the daily oil production from the oil sands comes from mining processes and the other half is produced mostly using steam assisted gravity drainage (SAGD). This method is effective at reducing the viscosity of the oil. However, the generation of steam requires a significant amount of energy. Thus, there is an ongoing effort to reduce the energy needed to produce oil from the oil sands. In this article the intermittent injection of a solvent, along with steam, is investigated as a means of reducing the amount of energy required to extract oil from the Canadian oil sands. A simulation-based study examined the effect of the type of solvent, the cycles’ duration, the solvent concentration and the number of cycles. The simulations covered a time span of 10 years during which several different solvents (methane, ethane, propane, butane, pentane, hexane, and CO2) were injected under varying injection schedules. The solvents that were investigated are compounds that are likely to be readily available at a heavy oil production site. The solvent injection periods ranged from six to 24 months in length. The results reveal that SAGD combined with intermittent injection of hexane resulted in the most significant improvement to the cumulative oil production and in the cumulative energy-oil ratio (cEOR). Compared to SAGD without solvent injection, the cumulative oil production was increased by 45% and the cEOR was reduced by 23%. It was also seen that the performance of the proposed process is highly dependent on the resulting physical properties of the solvent-bitumen mixture. Finally, a simplified economic analysis also identified SAGD with intermittent hexane injection as the scheme that resulted in the highest net present value. Compared to SAGD without solvent injection, the intermittent injection of hexane led to an 85% increase in the net present value.

Background: Targeted next generation sequencing (NGS) panels are increasingly being used in clinical genomics to increase capacity, throughput and affordability of gene testing. Identifying whole exon deletions or duplications (termed exon copy number variants, ‘exon CNVs’) in exon-targeted NGS panels has proved challenging, particularly for single exon CNVs. Methods: We developed a tool for the Detection of Exon Copy Number variants (DECoN), which is optimised for analysis of exon-targeted NGS panels in the clinical setting. We evaluated DECoN performance using 96 samples with independently validated exon CNV data. We performed simulations to evaluate DECoN detection performance of single exon CNVs and to evaluate performance using different coverage levels and sample numbers. Finally, we implemented DECoN in a clinical laboratory that tests BRCA1 and BRCA2 with the TruSight Cancer Panel (TSCP). We used DECoN to analyse 1,919 samples, validating exon CNV detections by multiplex ligation-dependent probe amplification (MLPA). Results: In the evaluation set, DECoN achieved 100% sensitivity and 99% specificity for BRCA exon CNVs, including identification of 8 single exon CNVs. DECoN also identified 14/15 exon CNVs in 8 other genes. Simulations of all possible BRCA single exon CNVs gave a mean sensitivity of 98% for deletions and 95% for duplications. DECoN performance remained excellent with different levels of coverage and sample numbers; sensitivity and specificity was >98% with the typical NGS run parameters. In the clinical pipeline, DECoN automatically analyses pools of 48 samples at a time, taking 24 minutes per pool, on average. DECoN detected 24 BRCA exon CNVs, of which 23 were confirmed by MLPA, giving a false discovery rate of 4%. Specificity was 99.7%. Conclusions: DECoN is a fast, accurate, exon CNV detection tool readily implementable in research and clinical NGS pipelines. It has high sensitivity and specificity and acceptable false discovery rate. DECoN is freely available at www.icr.ac.uk/decon.

To provide a useful community resource for orthogonal assessment of NGS analysis software, we present the ICR142 NGS validation series. The dataset includes high-quality exome sequence data from 142 samples together with Sanger sequence data at 730 sites; 409 sites with variants and 321 sites at which variants were called by an NGS analysis tool, but no variant is present in the corresponding Sanger sequence. The dataset includes 286 indel variants and 275 negative indel sites, and thus the ICR142 validation dataset is of particular utility in evaluating indel calling performance. The FASTQ files and Sanger sequence results can be accessed in the European Genome-phenome Archive under the accession number EGAS00001001332.