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Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and whole exome sequencing data from 752 individuals with sporadic IPF and 119,055 UK Biobank controls, we performed a variant-level exome-wide association study (ExWAS) and gene-level collapsing analyses. Our variant-level analysis revealed a novel association between a rare missense variant in SPDL1 and IPF (NM_017785.5:g.169588475 G > A p.Arg20Gln; p = 2.4 × 10-7, odds ratio = 2.87, 95% confidence interval: 2.03-4.07). This signal was independently replicated in the FinnGen cohort, which contains 1028 cases and 196,986 controls (combined p = 2.2 × 10-20), firmly associating this variant as an IPF risk allele. SPDL1 encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. To the best of our knowledge, these results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.

Genome-wide association studies have uncovered thousands of common variants associated with human disease, but the contribution of rare variants to common disease remains relatively unexplored. The UK Biobank contains detailed phenotypic data linked to medical records for approximately 500,000 participants, offering an unprecedented opportunity to evaluate the effect of rare variation on a broad collection of traits1,2. Here we study the relationships between rare protein-coding variants and 17,361 binary and 1,419 quantitative phenotypes using exome sequencing data from 269,171 UK Biobank participants of European ancestry. Gene-based collapsing analyses revealed 1,703 statistically significant gene-phenotype associations for binary traits, with a median odds ratio of 12.4. Furthermore, 83% of these associations were undetectable via single-variant association tests, emphasizing the power of gene-based collapsing analysis in the setting of high allelic heterogeneity. Gene-phenotype associations were also significantly enriched for loss-of-function-mediated traits and approved drug targets. Finally, we performed ancestry-specific and pan-ancestry collapsing analyses using exome sequencing data from 11,933 UK Biobank participants of African, East Asian or South Asian ancestry. Our results highlight a significant contribution of rare variants to common disease. Summary statistics are publicly available through an interactive portal ( http://azphewas.com/ ).

An investigation is presented of the influence of gas-geodynamic phenomena related to coal and rock falls and the associated release of deposit gases during driving of research galleries 16a and 16b in deck 407/3 of the Szczyglowice part of the Knurow-Szczyglowice coal mine, Upper Silesia, Poland. Examples are provided of air-parameter transient states in the mine workings during gas-dynamic phenomena, e.g. after shocks and bumps, as recorded by gasometry monitoring system sensors. Registration of the concentration of methane and oxygen in the forehead during and after various events, and of the air speed in gallery 16b during these events is discussed., An investigation is presented of the influence of gas-geodynamic phenomena related to coal and rock falls and the associated release of deposit gases during driving of research galleries 16a and 16b in deck 407/3 of the Szczyglowice part of the Knurow-Szczyglowice coal mine, Upper Silesia, Poland. Examples are provided of air-parameter transient states in the mine workings during gas-dynamic phenomena, e.g. after shocks and bumps, as recorded by gasometry monitoring system sensors. Registration of the concentration of methane and oxygen in the forehead during and after various events, and of the air speed in gallery 16b during these events is discussed.

In order to evaluate hazards to mine workers during development works, an investigation of five occurrences, in 2016/7, of sudden methane outflows or outbursts of methane and rocks during roadway and preparatory workings in the Zofiowka part of Borynia-Zofiowka-Jastrzebie coal mine in Poland is presented. Data provided include schemes of development works and locations of sensors and devices in the main gate D-4 in seams 412lg+ld and 412lg, and in the tail gate B-3 in seam 407/1 at the development phase; and methane concentrations in the developing main gate D-4 (seam 412lg), in the return air and in the longwall D-2, in the exploratory tail gate D-2 (seam 412lg) and in the tail gate B-3 (seam 407/1)., In order to evaluate hazards to mine workers during development works, an investigation of five occurrences, in 2016/7, of sudden methane outflows or outbursts of methane and rocks during roadway and preparatory workings in the Zofiowka part of Borynia-Zofiowka-Jastrzebie coal mine in Poland is presented. Data provided include schemes of development works and locations of sensors and devices in the main gate D-4 in seams 412lg+ld and 412lg, and in the tail gate B-3 in seam 407/1 at the development phase; and methane concentrations in the developing main gate D-4 (seam 412lg), in the return air and in the longwall D-2, in the exploratory tail gate D-2 (seam 412lg) and in the tail gate B-3 (seam 407/1).

The Strata Mechanics Institute of the Polish Academy of Sciences has developed an automated system for measuring the concentration of methane, oxygen, carbon monoxide and carbon dioxide in the gob. Computer simulations have also been developed using a numerical model of the flow of the methane-air mixture to assess fire hazards in the gob. Continuous gas monitoring tests were carried out in the Myslowice-Wesola coal mine at varying distances from the line of a cave-in. It was found that modelling results of the initial air distribution and methane inflow correlated well with measured values. Modelled levels of oxygen and carbon dioxide in the gob were similar to measured results. Methane levels differed, however, possibly due to the positioning of the gob sensor., The Strata Mechanics Institute of the Polish Academy of Sciences has developed an automated system for measuring the concentration of methane, oxygen, carbon monoxide and carbon dioxide in the gob. Computer simulations have also been developed using a numerical model of the flow of the methane-air mixture to assess fire hazards in the gob. Continuous gas monitoring tests were carried out in the Myslowice-Wesola coal mine at varying distances from the line of a cave-in. It was found that modelling results of the initial air distribution and methane inflow correlated well with measured values. Modelled levels of oxygen and carbon dioxide in the gob were similar to measured results. Methane levels differed, however, possibly due to the positioning of the gob sensor.

The application of computational fluid-dynamic simulations to the analysis of methane flow transients in the longwall and adjacent goaf in Polish coal mines is described. Simultaneous recordings, are presented of methane concentrations and flow velocities at several points inside the longwall, at the crossing with the tailgate and within the tailgate. Calculations are made of transient flow of fresh air in 2-D models of the longwall and tailgate for U and Y ventilation systems and a 3-D model develpoed of the longwall area and the area of the adjacent goaf. The results of modelling show an evolution of methane concentration distribution during transients that is almost unachievable by means of measurements., The application of computational fluid-dynamic simulations to the analysis of methane flow transients in the longwall and adjacent goaf in Polish coal mines is described. Simultaneous recordings, are presented of methane concentrations and flow velocities at several points inside the longwall, at the crossing with the tailgate and within the tailgate. Calculations are made of transient flow of fresh air in 2-D models of the longwall and tailgate for U and Y ventilation systems and a 3-D model develpoed of the longwall area and the area of the adjacent goaf. The results of modelling show an evolution of methane concentration distribution during transients that is almost unachievable by means of measurements.

Around thirty Polish underground coal mines introduced the SMP hazard monitoring and ventilation control systems in the 1990s. These systems continuously monitor methane concentrations and electrical systems are automatically isolated if potentially explosive conditions are found. The systems also monitor carbon monoxide, carbon dioxide, smoke and oxygen levels, as well as air and rock temperatures, to give early warning of open fires and spontaneous combustion. They can also act as an expert system when personnel have to be evacuated, by indicated pre-programmed escape routes., Around thirty Polish underground coal mines introduced the SMP hazard monitoring and ventilation control systems in the 1990s. These systems continuously monitor methane concentrations and electrical systems are automatically isolated if potentially explosive conditions are found. The systems also monitor carbon monoxide, carbon dioxide, smoke and oxygen levels, as well as air and rock temperatures, to give early warning of open fires and spontaneous combustion. They can also act as an expert system when personnel have to be evacuated, by indicated pre-programmed escape routes.

Changes in barometric pressure in deep mines can affect ventilation air flows in workings. These changes can be due to surface weather conditions or underground operations such as changes in the running of ventilation fans, movements of cages in shafts, or the opening and closing of air stoppings to allow personnel or machinery to pass. Pressure measurements were taken over a two-year period at selected points in a downcast shaft, and the results presented and analysed. The results of measurements taken during the opening and closing of a long working are also presented and analysed. These results were used to validate a simple mathematical model of air flows in the workings., Changes in barometric pressure in deep mines can affect ventilation air flows in workings. These changes can be due to surface weather conditions or underground operations such as changes in the running of ventilation fans, movements of cages in shafts, or the opening and closing of air stoppings to allow personnel or machinery to pass. Pressure measurements were taken over a two-year period at selected points in a downcast shaft, and the results presented and analysed. The results of measurements taken during the opening and closing of a long working are also presented and analysed. These results were used to validate a simple mathematical model of air flows in the workings.

The ventilation monitoring system is based on continuous measurement of mine air parameters, with underground sensors delivering information on changes in the composition of mine air. This information is used for monitoring methane hazards and the early detection of fires. The SMP system used in Polish coal mines provides remote and continuous measurements and controls underground parameters and air leaks as well as controlling fans on the surface to reduce external air losses. A control system using air distribution by automatic stopping of fans and energy-saving control of the rotational speed by thyristors has been carried out for use during modernisation or closure of mines. Research is currently under way into improving safety and reducing the power consumption used for ventilation in Polish coal mines., The ventilation monitoring system is based on continuous measurement of mine air parameters, with underground sensors delivering information on changes in the composition of mine air. This information is used for monitoring methane hazards and the early detection of fires. The SMP system used in Polish coal mines provides remote and continuous measurements and controls underground parameters and air leaks as well as controlling fans on the surface to reduce external air losses. A control system using air distribution by automatic stopping of fans and energy-saving control of the rotational speed by thyristors has been carried out for use during modernisation or closure of mines. Research is currently under way into improving safety and reducing the power consumption used for ventilation in Polish coal mines.

Ventilation monitoring in Polish coal mines is based on continuous measurement of mine air parameters to monitor methane hazards and detect fires. These conditions are met by the SMP system, which supplies all underground devices and sensors from the surface so it is possible to continue measurements independently of the state of underground electric power networks. The system controls underground parameters and air leakage as well as fan parameters to reduce external air losses. Energy savings have been made by controlling the rotational speed of fans using thyristor cascade. Discussion is presented of safety improvements and reduction of power consumption for ventilation in Polish coal mines., Ventilation monitoring in Polish coal mines is based on continuous measurement of mine air parameters to monitor methane hazards and detect fires. These conditions are met by the SMP system, which supplies all underground devices and sensors from the surface so it is possible to continue measurements independently of the state of underground electric power networks. The system controls underground parameters and air leakage as well as fan parameters to reduce external air losses. Energy savings have been made by controlling the rotational speed of fans using thyristor cascade. Discussion is presented of safety improvements and reduction of power consumption for ventilation in Polish coal mines.

Experiments were carried out to investigate the propagation of gas disturbances in a mine ventilation network, the main aim being to estimate a coefficient for turbulent diffusion. Signals were recorded during the propagation of disturbances in methane, carbon monoxide and smoke concentrations; disturbances of methane, caused by switching off auxiliary fans and blasting in the longwall, were treated as natural gas markers and recorded at different points along the ventilation paths. It was found that the length of the gas disturbance impulse was proportional to the root of the distance from the disturbance source. The diffusion coefficient increases with velocity of air flow and depends very heavily on section inequality, reaching considerable values where there are obstacles in a working section., Experiments were carried out to investigate the propagation of gas disturbances in a mine ventilation network, the main aim being to estimate a coefficient for turbulent diffusion. Signals were recorded during the propagation of disturbances in methane, carbon monoxide and smoke concentrations; disturbances of methane, caused by switching off auxiliary fans and blasting in the longwall, were treated as natural gas markers and recorded at different points along the ventilation paths. It was found that the length of the gas disturbance impulse was proportional to the root of the distance from the disturbance source. The diffusion coefficient increases with velocity of air flow and depends very heavily on section inequality, reaching considerable values where there are obstacles in a working section.

Waste dumps are often used for recreational purposes and as a source of raw materials for road building and general construction. The presence of coal in the waste can present a fire hazard and a number of factors may result in spontaneous heating and ignition of material within the dumps. Monitoring and prompt detection of spontaneous heating processes is required so that preventive measures may be taken to avoid the occurrence of fires., Waste dumps are often used for recreational purposes and as a source of raw materials for road building and general construction. The presence of coal in the waste can present a fire hazard and a number of factors may result in spontaneous heating and ignition of material within the dumps. Monitoring and prompt detection of spontaneous heating processes is required so that preventive measures may be taken to avoid the occurrence of fires.

Discussion is presented of disturbances in the ventilation system, especially those caused by short circuits at the air stoppings in active longwalls. Such disturbances can have a violent character and the resulting disorders in air velocity can lead to significant disturbances in methane concentration in the recirculated air. Practice shows that awareness of ventilation engineers about the danger of these disturbances is growing and mines are increasingly introducing numerous safeguards against the consequences of such disturbances in their technical documentation. Three cases of an abnormal type of short circuit are discussed, along with their consequences in terms of lower velocity air flow and increased concentrations of methane. Two of these are the results of studies carried out after methane explosions and the third shows how to control problems with air flow., Discussion is presented of disturbances in the ventilation system, especially those caused by short circuits at the air stoppings in active longwalls. Such disturbances can have a violent character and the resulting disorders in air velocity can lead to significant disturbances in methane concentration in the recirculated air. Practice shows that awareness of ventilation engineers about the danger of these disturbances is growing and mines are increasingly introducing numerous safeguards against the consequences of such disturbances in their technical documentation. Three cases of an abnormal type of short circuit are discussed, along with their consequences in terms of lower velocity air flow and increased concentrations of methane. Two of these are the results of studies carried out after methane explosions and the third shows how to control problems with air flow.

Measurements of air flow rate and volume are required for monitoring mine ventilation, but fluctuations can occur in the instantaneous values recorded by sensors due to turbulent flow. Currently mines use data from air flow sensors in the methane protection systems and the electrical power supply is switched off when the air flow rate is reduced to below a critical value. Significant fluctuations in the value of the instantaneous air flow rate can result in situations where the use of an anemometer to control power supply shutdowns may lead to unjustified shutdowns with interruptions to mining operations as a result of machine unavailability. An approach is described involving the smoothing of the data obtained from ventilation monitoring and control systems to eliminate the effects of turbulence which have no impact on safety or long-term changes in ventilation., Measurements of air flow rate and volume are required for monitoring mine ventilation, but fluctuations can occur in the instantaneous values recorded by sensors due to turbulent flow. Currently mines use data from air flow sensors in the methane protection systems and the electrical power supply is switched off when the air flow rate is reduced to below a critical value. Significant fluctuations in the value of the instantaneous air flow rate can result in situations where the use of an anemometer to control power supply shutdowns may lead to unjustified shutdowns with interruptions to mining operations as a result of machine unavailability. An approach is described involving the smoothing of the data obtained from ventilation monitoring and control systems to eliminate the effects of turbulence which have no impact on safety or long-term changes in ventilation.

The exploitation of bump-prone coal beds is discussed in relation to the occurrence of shocks and tremors which induce gas dynamics phenomena. The phenomena can be considered as non-stationary states of the air parameters resulting from geometry changes in the excavations and the release of large amounts of gas. Such conditions occurred in the Zabrzr-Bielscowice mine, Poland, in 1996 and 1999, and a seismic eventoccurred in the area of longwall 841a at the Bielscowice in October 2009 which resulted in a rock slide. The development of an automatic gas monitoring system for measuring the extent and frequency of gas dynamics phenomena is described., The exploitation of bump-prone coal beds is discussed in relation to the occurrence of shocks and tremors which induce gas dynamics phenomena. The phenomena can be considered as non-stationary states of the air parameters resulting from geometry changes in the excavations and the release of large amounts of gas. Such conditions occurred in the Zabrzr-Bielscowice mine, Poland, in 1996 and 1999, and a seismic eventoccurred in the area of longwall 841a at the Bielscowice in October 2009 which resulted in a rock slide. The development of an automatic gas monitoring system for measuring the extent and frequency of gas dynamics phenomena is described.