A study of using cough sounds and deep neural networks for the early detection of Covid-19.

The current clinical diagnosis of COVID-19 requires person-to-person contact, needs variable time to produce results, and is expensive. It is even inaccessible to the general population in some developing countries due to insufficient healthcare facilities. Hence, a low-cost, quick, and easily accessible solution for COVID-19 diagnosis is vital. This paper presents a study that involves developing an algorithm for automated and noninvasive diagnosis of COVID-19 using cough sound samples and a deep neural network. The cough sounds provide essential information about the behavior of glottis under different respiratory pathological conditions. Hence, the characteristics of cough sounds can identify respiratory diseases like COVID-19. The proposed algorithm consists of three main steps (a) extraction of acoustic features from the cough sound samples, (b) formation of a feature vector, and (c) classification of the cough sound samples using a deep neural network. The output from the proposed system provides a COVID-19 likelihood diagnosis. In this work, we consider three acoustic feature vectors, namely (a) time-domain, (b) frequency-domain, and (c) mixed-domain (i.e., a combination of features in both time-domain and frequency-domain). The performance of the proposed algorithm is evaluated using cough sound samples collected from healthy and COVID-19 patients. The results show that the proposed algorithm automatically detects COVID-19 cough sound samples with an overall accuracy of 89.2%, 97.5%, and 93.8% using time-domain, frequency-domain, and mixed-domain feature vectors, respectively. The proposed algorithm, coupled with its high accuracy, demonstrates that it can be used for quick identification or early screening of COVID-19. We also compare our results with that of some state-of-the-art works.

Chest X-Ray Images to Differentiate COVID-19 from Pneumonia with Artificial Intelligence Techniques.

This paper presents an automated and noninvasive technique to discriminate COVID-19 patients from pneumonia patients using chest X-ray images and artificial intelligence. The reverse transcription-polymerase chain reaction (RT-PCR) test is commonly administered to detect COVID-19. However, the RT-PCR test necessitates person-to-person contact to administer, requires variable time to produce results, and is expensive. Moreover, this test is still unreachable to the significant global population. The chest X-ray images can play an important role here as the X-ray machines are commonly available at any healthcare facility. However, the chest X-ray images of COVID-19 and viral pneumonia patients are very similar and often lead to misdiagnosis subjectively. This investigation has employed two algorithms to solve this problem objectively. One algorithm uses lower-dimension encoded features extracted from the X-ray images and applies them to the machine learning algorithms for final classification. The other algorithm relies on the inbuilt feature extractor network to extract features from the X-ray images and classifies them with a pretrained deep neural network VGG16. The simulation results show that the proposed two algorithms can extricate COVID-19 patients from pneumonia with the best accuracy of 100% and 98.1%, employing VGG16 and the machine learning algorithm, respectively. The performances of these two algorithms have also been collated with those of other existing state-of-the-art methods.

Prophylactic Negative-pressure Dressings Reduce Wound Complications and Resource Burden After Emergency Laparotomies.

BACKGROUND: Surgical site infection (SSI) and wound breakdown after emergency laparotomy are common. They incur significant patient morbidity and health care costs. Negative-pressure dressings (NPDs) applied over closed incisions may minimize wound complications. However, its utility in the emergency setting is unknown. Here, we examined whether prophylactic NPD reduces wound complications after emergency laparotomies. METHODS: This is a retrospective review of consecutive emergency laparotomies undertaken at a university hospital from January 2018 to October 2019. Outcomes included the rate of SSI, wound breakdown, hospital-outreach service utilization, wound-related readmissions, and length of stay. Propensity score matched analysis was used to assess bias. RESULTS: A total of 227 emergency laparotomies were reviewed, 70 received NPD and 157 had conventional dressings (controls). SSI was identified in 33 (21.0%) patients from the control group and six (8.6%) from the NPD group (odds ratio 0.35, 95% confidence interval: 0.15-0.85, P = 0.022). Wound breakdown was observed in 21 (13.4%) patients from the control group and three (4.3%) from the NPD group (odds ratio 0.29, 95% confidence interval: 0.09-0.91, P = 0.040). The prophylactic benefit of NPD was most evident in clean-contaminated, contaminated, and dirty wounds. The NPD group had comparatively shorter postoperative stay, less outreach service utilization, and lower rates of wound-related readmissions. Multivariate analysis demonstrated that increasing age, body weight >75 kg, and wound contamination are independent predictors of wound complications, whereas NPD prevented SSI and wound breakdown. CONCLUSIONS: Prophylactic NPD significantly reduced wound complications after emergency laparotomy. This was associated with a substantial health resource saving. This study provides a strong rationale for randomized trials in this area.

Anti-Müllerian hormone (AMH) in the Diagnosis of Menstrual Disturbance Due to Polycystic Ovarian Syndrome.

Introduction: Polycystic ovarian syndrome (PCOS) is a leading cause of female subfertility worldwide, however due to the heterogeneity of the disorder, the criteria for diagnosis remains subject to conjecture. In the present study, we evaluate the utility of serum Anti-Müllerian hormone (AMH) in the diagnosis of menstrual disturbance due to PCOS. Method: Menstrual cycle length, serum AMH, gonadotropin and sex-hormone levels, total antral follicle count (AFC), body mass index (BMI) and ovarian morphology on ultrasound were analyzed in a cohort of 187 non-obese women, aged 18-35 years, screened for participation in a clinical trial of fertility treatment between 2013 and 2016 at a tertiary reproductive endocrine center. Results: Serum AMH was higher in women with menstrual disturbance when compared to those with regular cycles (65.6 vs. 34.8 pmol/L; P < 0.0001). The odds of menstrual disturbance was increased 28.5-fold (95% CI 3.6-227.3) in women with serum AMH >60 pmol/L, in comparison to those with an AMH < 15 pmol/L. AMH better discriminated women with menstrual disturbance (area under ROC 0.77) from those with regular menstrual cycles than AFC (area under ROC 0.67), however the combination of the two markers increased discrimination than either measure alone (0.83; 95% CI 0.77-0.89). Serum AMH was higher in women with all three cardinal features of PCOS (menstrual disturbance, hyperandrogenism, polycystic ovarian morphology) when compared to women with none of these features (65.6 vs. 14.6 pmol/L; P < 0.0001). The odds of menstrual disturbance were increased by 10.7-fold (95% CI 2.4-47.1) in women with bilateral polycystic morphology ovaries than those with normal ovarian morphology. BMI was a stronger predictor of free androgen index (FAI) than either AMH or AFC. Conclusion: Serum AMH could serve as a useful biomarker to indicate the risk of menstrual disturbance due to PCOS. Women with higher AMH levels had increased rates of menstrual disturbance and an increased number of features of PCOS.

Establishing reproductive potential and advances in fertility preservation techniques for XY individuals with differences in sex development.

BACKGROUND: Discordance between gonadal type and gender identity has often led to an assumption of infertility in patients with differences in sex development (DSD). However, there is now greater recognition of fertility being an important issue for this group of patients. Currently, gonadal tissue that may have fertility potential is not being stored for individuals with DSD and, where gonadectomy forms part of management, is often discarded. The area of fertility preservation has been predominantly driven by oncofertility which is a field dedicated to preserving the fertility of patients undergoing gonadotoxic cancer treatment. The use of fertility preservation techniques could be expanded to include individuals with DSD where functioning gonads are present. METHODS: This is a systematic literature review evaluating original research articles and relevant reviews between 1974 and 2018 addressing DSD and fertility, in vitro maturation of sperm, and histological/ultrastructural assessment of gonadal tissue in complete and partial androgen insensitivity syndrome, 17ß-hydroxysteroid dehydrogenase type 3 and 5α-reductase deficiency. CONCLUSION: Successful clinical outcomes of ovarian tissue cryopreservation are paving the way for similar research being conducted using testicular tissue and sperm. There have been promising results from both animal and human studies leading to cryopreservation of testicular tissue now being offered to boys prior to cancer treatment. Although data are limited, there is evidence to suggest the presence of reproductive potential in the gonads of some individuals with DSD. Larger, more detailed studies are required, but if these continue to be encouraging, individuals with DSD should be given the same information, opportunities and access to fertility preservation as other patient groups.

A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

STUDY QUESTION: Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)? SUMMARY ANSWER: A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS. WHAT IS KNOWN ALREADY: Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. STUDY DESIGN, SIZE, DURATION: Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence. MAIN RESULTS AND THE ROLE OF CHANCE: A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH-response following the second kisspeptin dose, which appeared to be dependent on the LH-response following the first kisspeptin injection. Patients who had a lower LH-rise following the first dose of kisspeptin had a more substantial 'rescue' LH-response following the second dose of kisspeptin. The variable LH-response following the second dose of kisspeptin resulted in a greater proportion of patients achieving an oocyte yield ≥60%, but without also increasing the frequency of ovarian over-response and moderate OHSS (Single: 1/31, 3.2%, Double: 0/31, 0%). LIMITATIONS, REASONS FOR CAUTION: Further studies are warranted to directly compare kisspeptin-54 to more established triggers of oocyte maturation. WIDER IMPLICATIONS OF THE FINDINGS: Triggering final oocyte maturation with kisspeptin is a novel therapeutic option to enable the use of fresh embryo transfer even in the woman at high risk of OHSS. STUDY FUNDING/COMPETING INTEREST(S): The study was designed, conducted, analysed and reported entirely by the authors. The Medical Research Council (MRC), Wellcome Trust & National Institute of Health Research (NIHR) provided research funding to carry out the studies. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov identifier NCT01667406. TRIAL REGISTRATION DATE: 8 August 2012. DATE OF FIRST PATIENT'S ENROLMENT: 10 August 2015.

The medical and ethical challenges of fertility preservation in teenage girls: a case series of sickle cell anaemia patients prior to bone marrow transplant.

Cryopreservation of oocytes has been proposed as a way of storing gametes in young patients at high risk of infertility and premature ovarian failure. Recent advances in cryobiology have yielded promising results, leading to oocyte cryopreservation becoming a mainstay of fertility preservation. In this case series, we describe the feasibility of performing ovarian stimulation, and the ethical challenges faced, in teenage girls, aged 14-18 years, prior to undergoing bone marrow transplant for sickle cell anaemia. All eight consecutive cases completed ovarian stimulation and oocyte retrieval with mature oocytes being found and cryopreserved for each patient. The mean dose of gonadotrophin stimulation was 2134.38 IU (95% CI 1593.34-2675.4) and the mean duration of treatment was 11 days (95% CI 10.02-11.98). The mean number of oocytes retrieved was 14.88 (95% CI 7.39-22.36), of which a mean of 12.13 (95% CI 4.72-19.54) oocytes were mature and cryopreserved. There was one case of moderate ovarian hyperstimulation syndrome that required hospital admission for supportive treatment. Oocyte cryopreservation is a technique that can be successfully employed after the retrieval of mature oocytes from the peripubertal ovary, restoring hope to these patients, and their families, of having their own genetic children in the future.

Optimization of influential nutrients during direct cellulose fermentation into hydrogen by Clostridium thermocellum.

Combinatorial effects of influential growth nutrients were investigated in order to enhance hydrogen (H2) production during direct conversion of cellulose by Clostridium thermocellum DSM 1237. A central composite face-centered design and response surface methodology (RSM) were applied to optimize concentrations of cellulose, yeast extract (YE), and magnesium chloride (Mg) in culture. The overall optimum composition generated by the desirability function resulted in 57.28 mmol H2/L-culture with 1.30 mol H2/mol glucose and 7.48 mmol/(g·cell·h) when cultures contained 25 g/L cellulose, 2 g/L YE, and 1.75 g/L Mg. Compared with the unaltered medium, the optimized medium produced approximately 3.2-fold more H2 within the same time-frame with 50% higher specific productivity, which are also better than previously reported values from similar studies. Nutrient composition that diverted carbon and electron flux away from H2 promoting ethanol production was also determined. This study represents the first investigation dealing with multifactor optimization with RSM for H2 production during direct cellulose fermentation.

Community perceptions of a rural medical school: a pilot qualitative study.

BACKGROUND: This paper explores local community perceptions of a relatively new rural medical school. For the purposes of this paper, community engagement is conceptualized as involvement in planning, delivering, and evaluating the medical program. Although there are several reviews of patient involvement in medical curricula development, this study was designed to pilot an approach to exploring the perspectives of well members of the community in the transition of institutional policy on community engagement to one medical school. METHODS: An advertisement in the local newspaper invited volunteers to participate in a telephone interview about the new medical school. An independent researcher external to the medical school conducted the interviews using a topic guide. Audio recordings were not made, but detailed notes including verbatim statements were recorded. At least two research team members analyzed interview records for emergent themes. Human research ethics approval was obtained. RESULTS: Twelve interviews were conducted. Participants offered rich imaginings on the role of the school and expectations and opportunities for students. Most participants expressed strong and positive views, especially in addressing long-term health workforce issues. It was considered important that students live, mix, and study in the community. Some participants had very clear ideas about the need of the school to address specified needs, such as indigenous health, obesity, aging, drug and alcohol problems, teenage pregnancy, ethnic diversity, and working with people of low socioeconomic status. CONCLUSION: This study has initiated a dialogue with potential partners in the community, which can be built upon to shape the medical school's mission and contribution to the society it serves. The telephone interview approach and thematic analysis yielded valuable insights and is recommended for further studies. Our study was limited by its small study size and the single recruitment source. The community is a rich resource for medical education, but there is a dearth of literature on the perspectives of the community and its role in medical education.

Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women.

OBJECTIVE: To estimate the probability of live birth, adverse treatment outcome, and extremes of ovarian response at different antral follicle count (AFC) cutoff levels in a large prospective cohort of women undergoing IVF treatment. DESIGN: Prospective study. SETTING: University-based assisted conception unit. PATIENT(S): A total of 1,012 consecutive subjects of all ages undergoing their first cycle of assisted reproductive techniques. INTERVENTION(S): Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Live birth rate, poor ovarian response, and ovarian hyperstimulation syndrome (OHSS). RESULT(S): Analysis was performed in 1,012 subjects. Both age (r = 0.88) and AFC (r = 0.92) thresholds show significant linear relationship with the probability of live birth, but AFC demonstrates a stronger correlation. At AFC quartiles of 3-10, 11-15, 16-22, and ≥23, the mean live birth rates were 23%, 34%, 39%, and 44%, respectively. No live birth was observed in women with AFC <4. Antral follicle count was predictive of ovarian response, with a 67% likelihood of poor ovarian response for AFC ≤4. Although the risk of moderate or severe OHSS is 2.2% with AFC of ≤24, the risk increases to 8.6% at AFC of ≥24. The risk of OHSS increases further to 11% if there are signs and symptoms of polycystic ovary syndrome. CONCLUSION(S): Although age and AFC are significantly correlated with live birth, AFC demonstrates a stronger correlation. Antral follicle count thresholds are useful to predict live birth rates and risks of poor ovarian response and OHSS during IVF treatment.

Influence of initial cellulose concentration on the carbon flow distribution during batch fermentation by Clostridium thermocellum ATCC 27405.

The objective of this research was to understand how carbon loading influences hydrogen (H(2)) synthesis and metabolic flow patterns in the thermophilic, cellulolytic bacterium, Clostridium thermocellum. C. thermocellum was cultivated in batch cultures with high (5 g L(-1)) and low (1 g L(-1)) initial concentrations of alpha-cellulose at 60 degrees C. The growth rate of C. thermocellum was 22% lower (0.15 h(-1)) in cultures with low-cellulose concentration compared with cultures with high-cellulose concentrations. Although substrate depletion coincided with the end of log-growth in low-cellulose cultures, the prime reason for growth arrest in high-cellulose cultures was not identified. Ethanol, acetate, and formate were the major soluble end-products with concomitant release of H(2) and CO(2) under both conditions. Lactate appeared during the late log phase in high-carbon cultures when pH dropped below 6.4 and became the major end-product in stationary phase. During the exponential phase of cell growth, significantly higher yields for H(2) and acetate (1.90 +/- 0.14 and 1.11 +/- 0.04 mol/mol glucose equivalent, respectively) were obtained from low-cellulose cultures compared to those from high-cellulose cultures. The maximum specific rate of H(2) production, 6.41 +/- 0.13 mmol H(2)/g dry cell/h, obtained during the exponential phase from low-carbon cultures was about 37% higher than that obtained from high-carbon cultures.

Formate synthesis by Clostridium thermocellum during anaerobic fermentation.

We have detected formate synthesis by Clostridium thermocellum 27405 cultured in both cellobiose and alpha-cellulose. While formate synthesis has been reported for one strain of C. thermocellum (strain I-1-B), numerous studies of C. thermocellum 27405 fermentation, conducted under different growth conditions, failed to detect the presence of formate. Thus, the status of formate synthesis as a fermentation end product by C. thermocellum has been uncertain. Formate synthesis competes with the synthesis of hydrogen (H2) as a fermentation end product, and thus would negatively impact H2 yields in processes designed to generate H2 from biomass. Understanding the mechanism of formate synthesis is the first step in devising means of mitigating its production. Transcription of putative pfl, fnr, and adhE genes, encoding pyruvate formate-lyase (PFL), PFL-activating enzyme (PFL-AE), and alcohol dehydrogenase E (ADH-E) enzymes, respectively, were detected by reverse transcriptase polymerase chain reactions using total RNA extracted from stationary phase C. thermocellum cultured on cellobiose. The PCR products observed correspond to the expected amplicon sizes. Nucleotide sequence analysis of the cloned PCR products followed by BLAST analyses confirmed their identity. Formate production was detected throughout growth, and PFL enzyme activity was detected in late log and stationary phase (OD600 = 0.7 and 0.9, respectively) in extracts of C. thermocellum cultured on cellobiose. BLAST analyses revealed that C. thermocellum PFL and PFL-AE have greater amino acid sequence identity with equivalent enzymes from Bacillus and Thermocynechococcus species than with other Clostridium species, but C. thermocellum ADH-E has greater amino acid sequence identity with Clostridium species.

Effect of substrate loading on hydrogen production during anaerobic fermentation by Clostridium thermocellum 27405.

We have investigated hydrogen (H2) production by the cellulose-degrading anaerobic bacterium, Clostridium thermocellum. In the following experiments, batch-fermentations were carried out with cellobiose at three different substrate concentrations to observe the effects of carbon-limited or carbon-excess conditions on the carbon flow, H2-production, and synthesis of other fermentation end products, such as ethanol and organic acids. Rates of cell growth were unaffected by different substrate concentrations. H2, carbon dioxide (CO2), acetate, and ethanol were the main products of fermentation. Other significant end products detected were formate and lactate. In cultures where cell growth was severely limited due to low initial substrate concentrations, hydrogen yields of 1 mol H2/mol of glucose were obtained. In the cultures where growth ceased due to carbon depletion, lactate and formate represented a small fraction of the total end products produced, which consisted mainly of H2, CO2, acetate, and ethanol throughout growth. In cultures with high initial substrate concentrations, cellobiose consumption was incomplete and cell growth was limited by factors other than carbon availability. H2-production continued even in stationary phase and H2/CO2 ratios were consistently greater than 1 with a maximum of 1.2 at the stationary phase. A maximum specific H2 production rate of 14.6 mmol g dry cell(-1) h(-1) was observed. As cells entered stationary phase, extracellular pyruvate production was observed in high substrate concentration cultures and lactate became a major end product.